Information

8: Peptide Bonds, Polypeptides & Proteins - Biology

8: Peptide Bonds, Polypeptides & Proteins - Biology


We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

8: Peptide Bonds, Polypeptides & Proteins

Nice question! As you already know, DNA is always shown in 5'$ ightarrow$3' direction because it is always synthesized in this direction (amino acids are joined by CO-NH peptide bond). So, a polypeptide looks like this (source):

In fact, if you just look at the polypeptide in the reverse direction, you could view it in C terminus to N terminus direction. But we don't do so because that is not the conventional direction of the polypeptide's biosynthesis.

Tracing the Roots: To know why there is no "reverse" peptide bond (NH-CO), we first need to know how peptide bonds are formed in polypeptides. Polypeptides are formed in ribosome, and the process of formation of peptide bond occurs in the peptidyl transferase complex of ribosome. Since ribosome is a ribozyme, this reaction is also catalyzed by the catalytic sites of RNA (i.e. 2'-OH) instead of proteins. See the image below for the mechanism (from Marina V. Rodina):

As visible from the diagram, nitrogen (in -NH2) from acceptor tRNA (A site) attacks the ester linkage at the peptidyl tRNA (P site). Carboxylic carbon cannot attack the nitrogen (for "reverse" bond formation) because it is already in ester linkage. One might ask then "if the nitrogen was joined to tRNA at P-site, the carboxylic carbon could have attacked on amino acid at A-site. Why is amino acid not joined to tRNA by the amine nitrogen?" To know why it is so, lets go a step further and see how tRNAs are charged i.e. how aminoacyl tRNA synthetase works. Aminoacyl tRNA synthetase charges tRNA in a two-step reaction. For displaying mechanism, I will take the example of histidyl-tRNA synthetase (diagrams from Proteopedia):

amino acid + ATP &rarr aminoacyl-AMP + PPi

aminoacyl-AMP + tRNA &rarr aminoacyl-tRNA + AMP

As is clearly visible now, whether amine nitrogen or carboxylic carbon will attach to phosphate of ATP is decided in the first step. See the image again:


TRANSLATION (PROTEIN SYNTHESIS)

The biosynthesis of a protein or a polypeptide in a living cell is called as translation. The genetic information stored in DNA is passed to RNA (transcription) and it expressed in the language of proteins (translation). Translation occurs by similar mechanisms of prokaryotes and eukaryotes and it is described in five stages.

  1. Activation of amino acids (Aminoacyl tRNA synthetases).
  2. Initiation (Binding of a ribosome to mRNA).
  3. Elongation (Repeated addition of amino acids).
  4. Termination and release (Release of new polypeptide chain).
  5. Folding and post-translational processing (polypeptide must fold into three- dimensional conformation and it may undergo enzymatic processing).

Translation requires the use of energy by the cl which is provided by the hydrolysis of GTP and ATP. Guanosine-triphosphate (GTP) is used for ribosome movement and in binding of accessory factors. Adenosine triphosphate (ATP) is used to change tRNAs and in removing secondary structure from mRNA. Protein synthesis requires many components such as amino acids, ribosomes, mRNA, tRNA, protein factors and energy sources (ATP and GTP).

Activation of Amino Acids:

Cytoplasm contains 20 different amino acids and they are activated by a specific activating enzyme known as the aminoacyl synthetase and ATP before the attachment with its specific tRNA. The correct amino acid is attached to the tRNA by a type of enzyme called an aminoacyl-tRNA synthetase (aminoacylation/charging). The process of transfer of activated amino acids to tRNA is called charging of tRNA. The tRNAs are specific to theⅠr specific amino aminoacyl-tRNA synthase enzyme. Enzyme than catalyses a reaction in which the ATP loses two phosphates and is coupled to the amino acid as AMP to form aminoacyl AMP (Fig. 8.13). The tRNA molecule binds to the enzyme, which transfers the amino acid from the aminoacyl – AMP to the tRNA to form aminoacyl-tRNA. The aminoacyl-tRNA molecule produced is then reⅠeased from the enzyme.

The first step in translation involves the binding of the small ribosomal subunit to the mRNA and use of specific initiating tRNA molecule. In prokaryotes, tRNA molecule is acylated with the modified amino acid (N-formyl methionine). Both tRNA fMet recognize the codon AUG but only tRNA fMet is used for initiation. The tRNA fMet molecule is first acylated with methionine and an enzyme adds a formyl group to the amino group of the methionine. In eukaryotes, the initiating tRNA molecule is charged with methionine but formylation does not occur.

The initiation of polypeptide synthesis in prokaryotes requires 30S and S0S ribosomal subunit, mRNA, tRNA fMet ,initiation factors(IF-1,IF-2 and IF-3),GTP and magnesium ions. Eukaryotic cells have at least nine initiation factors (eⅠF2, eⅠF23, eⅠF 3, eⅠF4A, eⅠF4B, eⅠF4E ,eⅠF4G, eⅠF5, eⅠF6). The initiation factors bind to 30S ribosomal subunit in the presence of GTP to form 30S-ⅠF complex. The 30S-ⅠF complex binds to the region of the mRNA with The AUG initiation codon. Each mRNA at its untranslational region consists of a ribosome binding site for every polypeptide in the form of polycistronic message. This ribosome binding site (5’- AGGAGGA-3′) is known as Shine-Dalgarno sequence which is important in the binding of mRNA to the 30S-ⅠF complex.

The ribosome has three important binding sites such as aminoacyl-tRNA binding site (A) peptide binding site (P) and exit site (E). The A site receives all the incoming charged tRNA.whereas the P site possesses the previous tRNA with the new polypeptides. The tRNA fMet directly binds with ‘P’ site. The E site is the site from which the ‘uncharged’ tRNAs leave during elongation. Factor IF-1 binds at the A site and prevents tRNA binding at this site during initiation.

The IF-2 which has combined with GTP, permits the initiator tRNA (tRNA fMet ) to bind to the 30S ribosomal subunit (Fig. 8.14). A 30S ribosome unit is bound with 505 unit to produce 70S initiation complex. Similarly, in eukaryotes the 405 initiation complex is attached to 605 ribosomal subunit and forms the complete 805 initiation complex. The GTP bond to IF2 is hydrolyzed to GDP and Pi, which are released from the complex. All three initiation factors also depart from the ribosome. The initiation complex is now ready for elongation.

Elongation requires the initiation complex, aminoacyl-tRNAs, GTP and elongation factors. The addition of amino acids to the growing polypeptide chain as per codon on mRNA is called elongation of chain. Elongation of chain occur in three phases.

  1. Binding of aminoacyl- RNA.
  2. Peptide bond formation.
  3. Translocation.
  4. Binding of aminoacyl-tRNA: The ribosome (70S) possess the tRNA in the P-site, whereas the A site is free to receive the next aminoacyl-tRNA according to the codons on MRNA. Aminoacyl-tRNA bind to the protein elongation factor EF-Tu and a molecule of GTP. GTP hydrolysis releases EF-Tu-GDP and EF-Tu is recycled. Second elongation factor (EF-Ts) binds to EF-Tu and displaces the GDP (Fig, 8.15). GTP binds to the EF-Tu-EF-Ts complex to produce EF-Tu-GTP complex by releasing EF-Ts. Aminoacyl-TRNA binds to the EF-Tu-GTP and that complex can bind to the A site in the ribosome.
  5. Peptide bond formation: A peptide bond is formed between the two amino acids bounded to their TRNAS to the A and P sites on the ribosome. First, the bond between the amino acid and the tRNA in the P site is breaked and form free fMet and its TRNA. The peptide bond is formed between the free fMet and the Ser attached to the tRNA in the A site (Fig. 8.15). The enzyme peptidyl transferase catalyses the formation of peptide bond.
  6. Translocation: The ribosome moves to the next codon of the mRNA (towards 3′-end) after the formation of peptide bond. This process is called translocation. Translocation requires the activity of another protein elongation factor, EF-G (In eukaryotes, eEF-2). An EF- G-GTP complex binds to the ribosome and GTP is hydrolyzed to supplies energy to move mRNA. Translocation of ribosome occurs along with displacement of the uncharged 1RNA away from the ‘P’ site.

Termination and Release:

The polypeptide chain is continuously elongated until a termination codon on mRNA reaches to ribosome. The termination of translation is signaled by one of three stop cadons such as UAA, UAG and UGA. The ribosome recognize a stop codon with the help of proteins called termination factors or release factors (RF). In prokaryotes, there are three release factors (RF-1, RF-2, RF-3). RF-1 recognizes UAA and UAG and RF-2 recognizes UAA and UGA. The RF-3 activates the RF-1 and RF-2, hence, it is called ‘stimulatory(s) factor’. In eukaryotes,there is only one RF protein (eRF-1) which is active with codons UAA, UAG and UGA.

The specific termination events triggered by the release factors are release of the polypeptide from the tRNA in the P-site of the ribosome, release of the tRNA from the ribosome and the dissociation of the two ribosomal subunits and the RF from the mRNA.

Folding and post-translation processing:

After release, some of the processing events occur in the polypeptide chain. These modifications include protein folding, trimming by proteolytic degradation, intein splicing and covalent changes which are collectively known as post-translational modifications. Many different chemical modifications of the side chains of amino acids or the amino and carboxyl termini of proteins are found. Modifications may involve addition of small groups such as methylation, phosphorylation, acetylation and hydroxylation. Some modifications may occur by the addition of larger molecular structures such as lipid and oligosaccharides.


8: Protein Synthesis on the Ribosome

  • Contributed by Tim Soderberg
  • Emeritus Associate Professor of Chemistry at University of Minnesota Morris

Recall from section 1.3D that the 'peptide bonds' which link amino acids to form polypeptides and proteins are in fact amide functional groups. The figure below shows the first four amino acid residues in a protein, starting at the amino terminus.

Let&rsquos take a look at the chemistry behind the formation of a new peptide bond between the first two amino acids - which we will call (aa-1) and (aa-2) - in a growing protein molecule. This process takes place on the ribosome, which is essentially a large biochemical 'factory' in the cell, composed up of many enzymes and (RNA) molecules, and dedicated to the assembly of proteins. You will learn more in a biochemistry or cell biology course about the complex but fascinating process of ribosomal protein synthesis. For now, we will concentrate on the enzyme-catalyzed organic transformation that is taking place: the formation of an amide from a carboxylate and an amine.

We have seen amide-forming reactions before &ndash think back to the glutamine and asparagine synthetase reactions (section 11.5). The same ideas that we learned for those reactions hold true for peptide bond formation: the carboxylate group on a substrate amino acid must first be activated, and the energy for this activation comes from ATP.

The carboxylate group of aa-1 is first transformed to an acyl-AMP intermediate through a nucleophilic substitution reaction at the (alpha )-phosphate of ATP.

In the next step, the amino acid is transferred to a special kind of (RNA) polymer called transfer (RNA), or (tRNA) for short. We need not concern ourselves here with the structure of (tRNA) molecules- all we need to know for now is that the nucleophile in this reaction is a hydroxyl group on the terminal adenosine of a (tRNA) molecule. Because this (tRNA) molecule is specific to (aa-1), we will call it (tRNA-1)

The incoming nucleophile is an alcohol, thus what we are seeing is an esterification: an acyl substitution reaction between the activated carboxylate of (aa-1) and an alcohol on (tRNA-1) to form an ester.

This reaction, starting with activation of the amino acid, is catalyzed by a class of enzymes called aminoacyl-(tRNA) synthetases (there are many such enzymes in the cell, each one recognizing its own amino acid - (tRNA) pair).

The first amino acid is now linked via an ester group to (tRNA-1). The actual peptide bond-forming reaction occurs when a second amino acid (aa-2) also linked to its own (tRNA-2) molecule, is positioned next to the first amino acid on the ribosome. In another acyl substitution reaction, catalyzed by an enzymatic component of the ribosome called peptidyl transferase (EC 2.3.2.12), the amino group on (aa-2) displaces (tRNA1): thus, an ester has been converted to an amide (thermodynamically downhill, so ATP is not required).

This process continues on the ribosome, as one amino acid after another is added to the growing protein chain:

When a genetically-coded signal indicates that the chain is complete, an ester hydrolysis reaction &ndash as opposed to another amide formation - occurs on the last amino acid, which we will call (aa-n). This reaction is catalyzed by proteins called release factors (RFs).

This hydrolysis event frees the mature protein from the ribosome, and results in the formation of a free carboxylate group at the end of the protein (this is called the carboxy-terminus, or (C)-terminus of the protein, while the other end &ndash the &lsquostarting&rsquo end &ndash is called the (N)-terminus).


Proteins

You might associate proteins with muscle tissue, but in fact, proteins are critical components of all tissues and organs. A protein is an organic molecule composed of amino acids linked by peptide bonds. Proteins include the keratin in the epidermis of skin that protects underlying tissues, the collagen found in the dermis of skin, in bones, and in the meninges that cover the brain and spinal cord. Proteins are also components of many of the body’s functional chemicals, including digestive enzymes in the digestive tract, antibodies, the neurotransmitters that neurons use to communicate with other cells, and the peptide-based hormones that regulate certain body functions (for instance, growth hormone). While carbohydrates and lipids are composed of hydrocarbons and oxygen, all proteins also contain nitrogen (N), and many contain sulfur (S), in addition to carbon, hydrogen, and oxygen.

Microstructure of Proteins

Figure 7. Structure of an Amino Acid

Proteins are polymers made up of nitrogen-containing monomers called amino acids. An amino acid is a molecule composed of an amino group and a carboxyl group, together with a variable side chain. Just 20 different amino acids contribute to nearly all of the thousands of different proteins important in human structure and function. Body proteins contain a unique combination of a few dozen to a few hundred of these 20 amino acid monomers. All 20 of these amino acids share a similar structure (Figure 7). All consist of a central carbon atom to which the following are bonded:

  • a hydrogen atom
  • an alkaline (basic) amino group NH2 (see Table 1)
  • an acidic carboxyl group COOH (see Table 1)
  • a variable group

Notice that all amino acids contain both an acid (the carboxyl group) and a base (the amino group) (amine = “nitrogen-containing”). For this reason, they make excellent buffers, helping the body regulate acid–base balance. What distinguishes the 20 amino acids from one another is their variable group, which is referred to as a side chain or an R-group. This group can vary in size and can be polar or nonpolar, giving each amino acid its unique characteristics. For example, the side chains of two amino acids—cysteine and methionine—contain sulfur. Sulfur does not readily participate in hydrogen bonds, whereas all other amino acids do. This variation influences the way that proteins containing cysteine and methionine are assembled.

Figure 8. Peptide Bond. Different amino acids join together to form peptides, polypeptides, or proteins via dehydration synthesis. The bonds between the amino acids are peptide bonds.

Amino acids join via dehydration synthesis to form protein polymers (Figure 8). The unique bond holding amino acids together is called a peptide bond. A peptide bond is a covalent bond between two amino acids that forms by dehydration synthesis. A peptide, in fact, is a very short chain of amino acids. Strands containing fewer than about 100 amino acids are generally referred to as polypeptides rather than proteins.

The body is able to synthesize most of the amino acids from components of other molecules however, nine cannot be synthesized and have to be consumed in the diet. These are known as the essential amino acids.

Free amino acids available for protein construction are said to reside in the amino acid pool within cells. Structures within cells use these amino acids when assembling proteins. If a particular essential amino acid is not available in sufficient quantities in the amino acid pool, however, synthesis of proteins containing it can slow or even cease.

Shape of Proteins

Just as a fork cannot be used to eat soup and a spoon cannot be used to spear meat, a protein’s shape is essential to its function. A protein’s shape is determined, most fundamentally, by the sequence of amino acids of which it is made (Figure 9a). The sequence is called the primary structure of the protein.

Figure 9. The Shape of Proteins. (a) The primary structure is the sequence of amino acids that make up the polypeptide chain. (b) The secondary structure, which can take the form of an alpha-helix or a beta-pleated sheet, is maintained by hydrogen bonds between amino acids in different regions of the original polypeptide strand. (c) The tertiary structure occurs as a result of further folding and bonding of the secondary structure. (d) The quaternary structure occurs as a result of interactions between two or more tertiary subunits. The example shown here is hemoglobin, a protein in red blood cells which transports oxygen to body tissues.

Although some polypeptides exist as linear chains, most are twisted or folded into more complex secondary structures that form when bonding occurs between amino acids with different properties at different regions of the polypeptide. The most common secondary structure is a spiral called an alpha-helix. If you were to take a length of string and simply twist it into a spiral, it would not hold the shape. Similarly, a strand of amino acids could not maintain a stable spiral shape without the help of hydrogen bonds, which create bridges between different regions of the same strand (see Figure 9b). Less commonly, a polypeptide chain can form a beta-pleated sheet, in which hydrogen bonds form bridges between different regions of a single polypeptide that has folded back upon itself, or between two or more adjacent polypeptide chains.

The secondary structure of proteins further folds into a compact three-dimensional shape, referred to as the protein’s tertiary structure (see Figure 9c). In this configuration, amino acids that had been very distant in the primary chain can be brought quite close via hydrogen bonds or, in proteins containing cysteine, via disulfide bonds. A disulfide bond is a covalent bond between sulfur atoms in a polypeptide. Often, two or more separate polypeptides bond to form an even larger protein with a quaternary structure (see Figure 9d). The polypeptide subunits forming a quaternary structure can be identical or different. For instance, hemoglobin, the protein found in red blood cells is composed of four tertiary polypeptides, two of which are called alpha chains and two of which are called beta chains.

When they are exposed to extreme heat, acids, bases, and certain other substances, proteins will denature. Denaturation is a change in the structure of a molecule through physical or chemical means. Denatured proteins lose their functional shape and are no longer able to carry out their jobs. An everyday example of protein denaturation is the curdling of milk when acidic lemon juice is added.

The contribution of the shape of a protein to its function can hardly be exaggerated. For example, the long, slender shape of protein strands that make up muscle tissue is essential to their ability to contract (shorten) and relax (lengthen). As another example, bones contain long threads of a protein called collagen that acts as scaffolding upon which bone minerals are deposited. These elongated proteins, called fibrous proteins, are strong and durable and typically hydrophobic.

In contrast, globular proteins are globes or spheres that tend to be highly reactive and are hydrophilic. The hemoglobin proteins packed into red blood cells are an example (see Figure 9d) however, globular proteins are abundant throughout the body, playing critical roles in most body functions. Enzymes, introduced earlier as protein catalysts, are examples of this. The next section takes a closer look at the action of enzymes.

Proteins Function as Enzymes

If you were trying to type a paper, and every time you hit a key on your laptop there was a delay of six or seven minutes before you got a response, you would probably get a new laptop. In a similar way, without enzymes to catalyze chemical reactions, the human body would be nonfunctional. It functions only because enzymes function.

Enzymatic reactions—chemical reactions catalyzed by enzymes—begin when substrates bind to the enzyme. A substrate is a reactant in an enzymatic reaction. This occurs on regions of the enzyme known as active sites (Figure 10). Any given enzyme catalyzes just one type of chemical reaction. This characteristic, called specificity, is due to the fact that a substrate with a particular shape and electrical charge can bind only to an active site corresponding to that substrate.

Figure 10. Steps in an Enzymatic Reaction. (a) Substrates approach active sites on enzyme. (b) Substrates bind to active sites, producing an enzyme–substrate complex. (c) Changes internal to the enzyme–substrate complex facilitate interaction of the substrates. (d) Products are released and the enzyme returns to its original form, ready to facilitate another enzymatic reaction.

Binding of a substrate produces an enzyme–substrate complex. It is likely that enzymes speed up chemical reactions in part because the enzyme–substrate complex undergoes a set of temporary and reversible changes that cause the substrates to be oriented toward each other in an optimal position to facilitate their interaction. This promotes increased reaction speed. The enzyme then releases the product(s), and resumes its original shape. The enzyme is then free to engage in the process again, and will do so as long as substrate remains.

Other Functions of Proteins

Advertisements for protein bars, powders, and shakes all say that protein is important in building, repairing, and maintaining muscle tissue, but the truth is that proteins contribute to all body tissues, from the skin to the brain cells. Also, certain proteins act as hormones, chemical messengers that help regulate body functions, For example, growth hormone is important for skeletal growth, among other roles.

As was noted earlier, the basic and acidic components enable proteins to function as buffers in maintaining acid–base balance, but they also help regulate fluid–electrolyte balance. Proteins attract fluid, and a healthy concentration of proteins in the blood, the cells, and the spaces between cells helps ensure a balance of fluids in these various “compartments.” Moreover, proteins in the cell membrane help to transport electrolytes in and out of the cell, keeping these ions in a healthy balance. Like lipids, proteins can bind with carbohydrates. They can thereby produce glycoproteins or proteoglycans, both of which have many functions in the body.

The body can use proteins for energy when carbohydrate and fat intake is inadequate, and stores of glycogen and adipose tissue become depleted. However, since there is no storage site for protein except functional tissues, using protein for energy causes tissue breakdown, and results in body wasting.


Main parameters influencing the antimicrobial activities of plant AMPs

The structure�tivity relationship analysis of plant AMPs indicated that their amino acid residues, net charge, hydrophobicity, amphipathicity and structural features are the most important physicochemical and structural parameters for their antimicrobial activity (Bhattacharjya et al. 2009). In addition to these main factors, some external factors, such as pH, temperature, and metal ions, also affect the activities of plant AMPs. It is worth noting that all of these factors are interrelated, and a change in one factor would lead to concomitant but inadvertent alterations in others.

Amino acid residues

In general, AMPs are classified on the basis of their net charge as cationic peptides rich in arginine or lysine, and anionic AMPs rich in aspartic acid or glutamic acid. The amino acid sequence has a characteristic influence on the structure and function of the peptide. Changes in amino acid sequence, length, and net charge will affect the hydrophobicity of the short amphiphilic peptide and directly affect its antibacterial activity and cytotoxicity (Gong et al. 2019 Sprules et al. 2004). Some AMPs with multiple Arg residues may be internalized via the anionic sulfated glycosaminoglycan pathway, and Arg-lacking AMPs were reported to not interact with sulfated glycosaminoglycans (Poon et al. 2007 Tang et al. 2013 Torcato et al. 2013). Arginine can provide positive charges and forms a large number of electrostatic interactions compared to lysine. A previous study showed that variations in the levels of four amino acid residues, leucine, alanine, glycine, and lysine, in different host defense peptide families modulate peptide activities (Wang 2020). Introducing proline into some AMPs and the location of the proline are determining factors of AMP antitumor and antimicrobial activities as well as other bioactivities (Yan et al. 2018). Aspartic acid and glutamic acid residues in the anionic peptides can facilitate the binding of metal ions, which is necessary for their antimicrobial activity (Dashper et al. 2005). In addition, aromatic residues (mainly tryptophan) may be important determinants to anchor the antimicrobial peptides onto membranes (Fimland et al. 2002).

Net charge

It is known that most antimicrobial peptides possess a net positive charge, and this positive charge is believed to play a major role in the interaction between the antimicrobial peptides and negatively charged membrane phospholipids. This relationship between biological activity and charge is not linear, and there are some examples of direct, indirect, or even inverse relationships between the charge and biological activity. An increase in the charge of AMPs will increase their antibacterial activity against gram-negative and gram-positive pathogens, but a threshold was found beyond which an increase in the positive charge no longer augments this activity. An excessively high net charge will lead to increased hemolytic propensity and decreased antimicrobial activity (Dathe et al. 2001 Jiang et al. 2009 Wang et al. 2019).

Hydrophobicity

Hydrophobicity is another necessary parameter to ensure the antibacterial efficacy and cell selectivity of AMPs. However, some studies have shown that the hemolytic activity of AMPs increases with enhanced hydrophobicity (Liscano et al. 2019). The higher hydrophobicity of AMPs could increase their ability to penetrate deeper into the hydrophobic core of cell membranes. Studies have shown that increasing AMP hydrophobicity is generally associated with increasing antimicrobial activity within a certain range. Increasing the hydrophobicity of the hydrophobic face will increase the antimicrobial activity of AMPs. When the peptide-length-dependent threshold is exceeded, the hemolytic activity of an AMP significantly increases and its cell selectivity decreases (Gong et al. 2019 Uggerhøj et al. 2015).

Alpha-helix and amphipathicity

The α-helix is the most common conformation of the various secondary structures in AMPs. Amino acid substitutions that significantly damage the helical structures in peptides can lead to a decrease in antimicrobial activity (Lee et al. 2016). Most helical AMPs that adopt the oblique-orientated α-helical configuration invade microbial membranes partially, resulting in membrane destabilization and promoting effects such as membrane fusion, hemolysis, and the formation of non-bilayer lipid structures (Dennison et al. 2005 Gong et al. 2019 Juretić et al. 2019). The amphipathic nature of AMPs is closely related to the formation of α-helical structures. The helix spatially segregates hydrophilic and hydrophobic residues on opposing faces along its long axis, leading to the formation of amphiphilic structures. When AMPs interact with the bacterial membrane, the ability to maintain a balance between amphiphilic and hydrophobic properties is also responsible for the biological activity of oblique-orientated α-helices (Harris et al. 2006 Liang et al. 2020). Optimizing amphiphilicity without changing other structural parameters resulted in significantly increased bactericidal activity and cytotoxicity due to strengthened hydrophobic interactions and membrane affinity (Takahashi et al. 2010).

Other factors

In addition to the major factors mentioned in previous sections, there are many minor factors that need to be mentioned. One study has shown that the dimerization of β-sheet peptides could also increase the antimicrobial activity of AMPs by promoting a deeper penetration into the hydrophobic membrane core than would be allowed by monomeric peptides (Teixeira et al. 2012). The addition of metal ions can cause conformational helix changes, which can affect the hydrophobic region of the helix and AMP activity (Oard et al. 2006). Although anionic peptides are composed entirely of negatively charged residues, some AMPs can interact with microbial membranes by co-opting cationic metal ions to form salt bridges (Dashper et al. 2005 Dennison et al. 2018). pH plays a variable role in the interaction of AMPs and microbial membranes. Some studies have shown that a change in pH can significantly affect the antibacterial activity of AMPs, but pH can also affect the membrane lipid composition of bacteria and increase their resistance to AMPs (Dennison et al. 2016 Koo et al. 1998). It has been found that disulfide bonds and hydrogen bonds contribute to the stability of native-folded AMPs, and both types of bonds affect the activity of AMPs by influencing their folding stability (Ranade et al. 2020 Vila-Perelló et al. 2005). In addition to the chemical bonds mentioned in previous sections, a few others have been reported, such as thioether bonds, which are required for peptide maturation (Pham et al. 2020 Wieckowski et al. 2015). However, the structure�tivity relationship between these chemical bonds and AMPs is not clear. Future studies are required to more closely examine this relationship.


8: Peptide Bonds, Polypeptides & Proteins - Biology

SECTION I - CLASS DEFINITION

Class 930 consists of two wholly separable parts, cross -reference art collections 10-320 and digests 500-822. This class is intended to be used as a searching area for patents which disclose an identifiable peptide or protein sequence derived from at least four specified named amino acids. Rules of placement into these areas vary, and although any search in this class is optional, searching Class 930 is useful.

It should be noted that the patents in art collections 10-320 must contain an actual amino acid sequence. A patent containing a reference, in name only, to a peptide or protein compound with a known structure is not included. For example, though the amino acid sequence of insulin is well-known, unless a sequence of at least four amino acids from the insulin structure is shown in the patent, it is not included in these art collections.

The following steps pertain to placement and search.

(1) Compounds containing a modified or unusual amino acid (art collections 20 -25) are placed in all appropriate art collections.

(2) The sole presence of a nonpeptide or abnormal peptide link in a linear peptide is not considered an indication of a modified or unusual amino acid. (See art collection 30.)

(3) See only art collection 22 for halogen containing compounds which are radioactive.

(4) The sulfur contained in the compounds of art collection 24 must be other than, or must be in addition to, that naturally occurring in one or more of the natural amino acids, cysteine, cystine, methionine.

(5) Art collection 30 does not include those peptides which contain as the sole nonpeptide or abnormal peptide link, an interchain disulfide bridge.

(6) Compounds included in art collections 200 (bacterial), 220 (parasitic), and 220-224 (viral0, are only those homologous to the microorganism.

(7) Compounds containing a cys-cys disulfide bridge between nonadjacent cysteine residues are placed in art collection 280 with the exception of those compounds such as atrial natriuretic peptide, vasopressin, or others containing disulfide bridges which are appropriate for art collection 40-170.

(8) Art collection 270 does not include peptides or proteins which are cyclic solely due to intrachain disulfide bridges, nor does it include peptides or proteins which are appropriate for art collections 40-170.

(9) Art collection 320 is incomplete. It is intended as a repository for compounds which have been specifically modified to prevent enzymatic degradation, but which are not more appropriately placed in any of the other nonmainline art collections.

SECTION II - LINES WITH OTHER CLASSES AND WITHIN THIS CLASS

(A) CROSS-REFERENCE ART COLLECTIONS

Cross-reference art collections 10-320 are intended to be used as a searching area for those patents which disclose an identifiable peptide or protein consisting of a sequence of at least four amino acids covalently bound through at least one normal peptide link.

Due to the nature of this class, it is important that it be considered more as a term list than as a hierarchical schedule. The classification rules of hierarchy do not apply unless otherwise specified in the art collection definitions or unless specified by one art collection being indented under another, i.e., art collections 21-25 are indented under 20, art collections 141-145 are indented under 140.

Therefore, in this class, a peptide or protein compound is placed in all art collections, regardless of order in the schedule, where the concepts of the art collection definition include the compound, unless otherwise specified.

Digests 500-822 are being established as U.S. classifications and are equivalent to the European Patent Office"s C07K 5/00 - C07K 5/12B C07K 7/02 - C07K 7/10B C07K 7/50 - C07K 9/00F4 C07K 13/00 and C07K 99/00B - C07K 99/84 classifications.

The European Patent Office (EPO) uses a classification system which is based upon the International Patent Classification (IPC) system. The EPO allows its examiners to add "unofficial" or "alpha" classifications to the IPC in a manner similar to our examiners adding "unofficial" or "alpha" classifications to the U.S. Patent Classification system. With the addition of the "unofficials", the IPC becomes the European Patent Classification (EPC) system.

As U.S. (and other countries) patents are published, the EPO examiners receive them for placement into their search files. The EPO examiners do not depend upon the IPCs printed on the issuing documents for placement they reclassify each document anew. As a result of trilateral agreements, the U.S. regularly receives the new classification data from the EPO. This classification data allows us the capability to establish digests 500 - 822 as U. S. digests which are equivalent to the EPO classifications recited in the first paragraph and which contain the same U.S. patents which EPO examiners placed into their files.

No definitions are associated with these digests. The full extent of the types of documents intended to be classified in a digest are the titles and any attached notes.

Digests 500-822 are the first areas in the U.S. classification system which are resident in the Manual of Classification and present a classification scheme wherein all of the patents have been classified by another patent office into search areas created other than by U.S. personnel.

The creation of digests 500-822 and their incorporation in the Manual of Classification is a trial program to determine the effectiveness of additional data bases which contain U.S. patents as search areas. In addition this will be the first time that U.S. examiners will be able to search EPC classifications. It is the intent of Documentation to set up other areas of the EPC where it is believed that a search area may be useful.

Digests 500-822 have been presented in a manner generally consistent with the traditional presentation of search areas in the U.S. Manual of Classification. In some instances areas in the EPC have been omitted or arranged in a format to which U.S. examiners are accustomed. In other instances the EPC classification does not contain any U.S. patents. To complete a search of a concept in the EPC it would be advisable to search both the generic subclass and the more specific indented subclass.

Patents can be added to these classifications in the traditional manner, i.e., blue slips, miscellaneous transfer, or 14B card. They can be deleted by the present method of submitting a copy of the document along with a request to classification.

At the end of each digest presented between parentheses is the classification in the EPC which translates to the digest provided for that EPC classification. To distinguish between the IPC and EPC versions it is only necessary to note that the IPC does not contain alpha designations. An example of this difference is digest 610, which is denoted as C07K-99/22. Since the latter is devoid of an alpha character it is both an IPC and EPC classification, whereas C07K-99/22A (digest 611) has an alpha designator and can only be found in the EPC. The use of a slash in the EPC designation C07K-99/ is equivalent to the use of a color in the IPC C07K-99 for this area

It is intended to maintain these digests in a form that reflects the current status of the EPC. As patents are classified into the EPC we will update the present digests to reflect the addition of the newly added documents.

In digests 550-772 and 780-822, sequences modified by removal or addition of amino acids, by substitution of amino acids by others, or by a combination of these modifications, are classified as the parent peptide when the combined number of modifications totals less than 50% of the parent fragment. Fragments of these peptides containing at least 5 amino acids, modified or not as mentioned above, are classified as the parent peptide. In digests 590, 630, and 680, the brackets have been used to indicate the presence of a specified amino acid.

A glossary has been developed for Class 930 (section D of the main class definition). Terms in the GLOSSARY have been used consistently throughout the class. The following terms are applicable only to digests 500-822.

(1) LINEAR PEPTIDES (DIGESTS 790-822) may comprise rings formed through a hydroxy or a mercapto group of a hydroxy or a mercapto amino acid and the carboxyl group of another amino acid, (e.g., peptide lactones, etc.) but do not comprise rings which are formed only through peptide links.

(2) CYCLIC PEPTIDES (DIGESTS 532-549) are peptides comprising at least one ring formed only through peptide links the cyclisation may occur only through normal or abnormal peptide links, e.g., through the 4-amino group of 2,4-diamino-butanoic acid, etc. Cyclic compounds in which at least one link in the ring is a nonpeptide link are considered as linear peptides.

(C) AMINO ACID ABBREVIATIONS

For the purposes of all of Class 930, cross-reference art collections 10-320 and digests 500-822, the following amino acid abbreviations are applicable:

Abbreviations and Amino Acid Names

Ala = Alanine Arg = Arginine Asn = Asparagine Asp = Aspartic Acid (Aspartate) Asx = Aspartic Acid or Asparagine

Glu = Glutamic Acid (Glutamate) Gln = Glutamine Gix = Glutamine or Glutamic Acid Gly = Glycine

Phe = Phenylalanine Pro = Proline

Thr = Threonine Trp = Tryptophan Tyr = Tyrosine

SECTION III - GLOSSARY

For the purposes of all of Class 930, cross-reference art collections 10-320 and digests 500-822, the following terms are appropriate as defined:

Compounds in which at least one amino group and at least one carboxyl group are bound to the same carbon skeleton and the nitrogen atom of the amino group may form part of a ring.

Exists between an alpha-amino group of an amino acid and the carboxyl group - in position 1 - of another alpha amino acid.

ABNORMAL PEPTIDE LINK

Exists between a nonalpha-amino group of an amino acid and the carboxyl group - in position 1 - of an alpha-amino acid, or between an alpha-amino group of one amino acid and the carboxyl group - not in position 1 - of another amino acid.

Compounds containing a sequence of 4 to 100 amino acid units, which are bound through at least one normal peptide link.

Compounds containing an amino acid sequence of more than 100 amino acids, at least two of which are different, bound mostly through normal peptide links.


Proteins

Proteins are another class of enormously diverse organic molecules that are made from multiple units of simpler molecules arranged in chains. All proteins are made from combinations of the 20 amino acids show below. As shown below, each of these 20 amino acids has a central carbon (the alpha carbon) bonded to an amino group (-NH2 i.e., nitrogen bonded to two hydrogens) at one end and a carboxyl group ( -COOH) at the other end.

What distinguishes one amino acid from another is the side chain of atoms that is also bonded to the alpha carbon (designated "R-group on the right).

The primary structure of proteins results from linking together various combinations of these 20 amino acids with peptide bonds, which link the carboxyl group of one amino acid to the amino group of another amino acid.

Now imagine that dozens or even hundreds of amino acides are linked together in chains of varying length to create the primary structure of a protein. Proteins are sometimes referred to as polypeptides because they consist of chains of amino acids linked together with peptide bonds.


Polypeptide Structure

Polypeptides have four levels of structure and they are the following:

Primary structure

The primary structure is the sequence of amino acid in the polypeptide chain in line with the location of disulfide bonds. To take note of the primary structure of the polypeptide, you should write the amino acid sequence with the use of three letter abbreviations for amino acids.

Secondary structure

It pertains to the ordered arrangement of amino acids in the localized location of the polypeptide. The folding pattern is stabilized with the help of hydrogen bonds.

The two secondary structures are alpha helix and anti-parallel beta-pleated sheet. Periodic confirmations are vast but the two mentioned above are the most stable.

  • α-helix It is a right-handed spiral wherein every peptide bond is in the trans conformation.
  • β-pleated sheet It has extended polypeptide chain with a nearby chain that extends anti-parallel to each other. Every β-pleated sheet is trans and planar. A hydrogen bond may occur between the nearby polypeptide chains.

Tertiary structure

The tertiary structure has three dimensional atom arrangement in a single polypeptide chain. The tertiary structure is maintained by disulfide bonds which are formed between the side chains of cysteine.

It is formed through the oxidation of two thiol groups thereby forming a disulfide bond.

Quaternary structure

it is a term used to describe proteins consists of multiple polypeptide molecules. Each polypeptide molecule is called monomer.

Usually, proteins that have greater than 50,000 molecular weight have two or more noncovalently-linked monomers.

It is called quaternary structure because the arrangement of monomers in three-dimensional protein is in quaternary style. A perfect example is the hemoglobin protein.

Hemoglobin has four monomers which two α-chains each containing 141 amino acids and two β-chains and each contains 146 amino acids. (4, 5, 6, and 7)


BIO 140 - Human Biology I - Textbook

/>
Unless otherwise noted, this work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License..

To print this page:

Click on the printer icon at the bottom of the screen

Is your printout incomplete?

Make sure that your printout includes all content from the page. If it doesn't, try opening this guide in a different browser and printing from there (sometimes Internet Explorer works better, sometimes Chrome, sometimes Firefox, etc.).

Chapter 3

Organic Compounds Essential to Human Functioning

Learning Objectives

  • Identify four types of organic molecules essential to human functioning
  • Explain the chemistry behind carbon&rsquos affinity for covalently bonding in organic compounds
  • Provide examples of three types of carbohydrates, and identify the primary functions of carbohydrates in the body
  • Discuss four types of lipids important in human functioning
  • Describe the structure of proteins, and discuss their importance to human functioning
  • Identify the building blocks of nucleic acids, and the roles of DNA, RNA, and ATP in human functioning

Organic compounds typically consist of groups of carbon atoms covalently bonded to hydrogen, usually oxygen, and often other elements as well. Created by living things, they are found throughout the world, in soils and seas, commercial products, and every cell of the human body. The four types most important to human structure and function are carbohydrates, lipids, proteins, and nucleotides. Before exploring these compounds, you need to first understand the chemistry of carbon.

The Chemistry of Carbon

What makes organic compounds ubiquitous is the chemistry of their carbon core. Recall that carbon atoms have four electrons in their valence shell, and that the octet rule dictates that atoms tend to react in such a way as to complete their valence shell with eight electrons. Carbon atoms do not complete their valence shells by donating or accepting four electrons. Instead, they readily share electrons via covalent bonds.

Commonly, carbon atoms share with other carbon atoms, often forming a long carbon chain referred to as a carbon skeleton. When they do share, however, they do not share all their electrons exclusively with each other. Rather, carbon atoms tend to share electrons with a variety of other elements, one of which is always hydrogen. Carbon and hydrogen groupings are called hydrocarbons. If you study the figures of organic compounds in the remainder of this chapter, you will see several with chains of hydrocarbons in one region of the compound.

Many combinations are possible to fill carbon&rsquos four &ldquovacancies.&rdquo Carbon may share electrons with oxygen or nitrogen or other atoms in a particular region of an organic compound. Moreover, the atoms to which carbon atoms bond may also be part of a functional group. A functional group is a group of atoms linked by strong covalent bonds and tending to function in chemical reactions as a single unit. You can think of functional groups as tightly knit &ldquocliques&rdquo whose members are unlikely to be parted. Five functional groups are important in human physiology these are the hydroxyl, carboxyl, amino, methyl and phosphate groups (Table 1).

Table 1. Functional Groups Important in Human Physiology

Functional group Structural formula Importance
Hydroxyl &mdashO&mdashH Hydroxyl groups are polar. They are components of all four types of organic compounds discussed in this chapter. They are involved in dehydration synthesis and hydrolysis reactions
Carboxyl O&mdashC&mdashOH Carboxyl groups are found within fatty acids, amino acids, and many other acids.
Amino &mdashN&mdashH2 Amino groups are found within amino acids, the building blocks of proteins.
Methyl &mdashC&mdashH3 Phosphate groups are found within phospholipids and nucleotides.

Carbon&rsquos affinity for covalent bonding means that many distinct and relatively stable organic molecules nevertheless readily form larger, more complex molecules. Any large molecule is referred to as macromolecule (macro- = &ldquolarge&rdquo), and the organic compounds in this section all fit this description. However, some macromolecules are made up of several &ldquocopies&rdquo of single units called monomer (mono- = &ldquoone&rdquo -mer = &ldquopart&rdquo). Like beads in a long necklace, these monomers link by covalent bonds to form long polymers (poly- = &ldquomany&rdquo). There are many examples of monomers and polymers among the organic compounds.

Monomers form polymers by engaging in dehydration synthesis. As was noted earlier, this reaction results in the release of a molecule of water. Each monomer contributes: One gives up a hydrogen atom and the other gives up a hydroxyl group. Polymers are split into monomers by hydrolysis (-lysis = &ldquorupture&rdquo). The bonds between their monomers are broken, via the donation of a molecule of water, which contributes a hydrogen atom to one monomer and a hydroxyl group to the other.

Carbohydrates

The term carbohydrate means &ldquohydrated carbon.&rdquo Recall that the root hydro- indicates water. A carbohydrate is a molecule composed of carbon, hydrogen, and oxygen in most carbohydrates, hydrogen and oxygen are found in the same two-to-one relative proportions they have in water. In fact, the chemical formula for a &ldquogeneric&rdquo molecule of carbohydrate is (CH2O)n.

Carbohydrates are referred to as saccharides, a word meaning &ldquosugars.&rdquo Three forms are important in the body. Monosaccharides are the monomers of carbohydrates. Disaccharides (di- = &ldquotwo&rdquo) are made up of two monomers. Polysaccharides are the polymers, and can consist of hundreds to thousands of monomers.

Monosaccharides

A monosaccharide is a monomer of carbohydrates. Five monosaccharides are important in the body. Three of these are the hexose sugars, so called because they each contain six atoms of carbon. These are glucose, fructose, and galactose, shown in Figure 1a. The remaining monosaccharides are the two pentose sugars, each of which contains five atoms of carbon. They are ribose and deoxyribose, shown in Figure 1b.

Disaccharides

A disaccharide is a pair of monosaccharides. Disaccharides are formed via dehydration synthesis, and the bond linking them is referred to as a glycosidic bond (glyco- = &ldquosugar&rdquo). Three disaccharides (shown in Figure 2) are important to humans. These are sucrose, commonly referred to as table sugar lactose, or milk sugar and maltose, or malt sugar. As you can tell from their common names, you consume these in your diet however, your body cannot use them directly. Instead, in the digestive tract, they are split into their component monosaccharides via hydrolysis.

Figure 2: All three important disaccharides form by dehydration synthesis.

Watch the video linked to below to observe the formation of a disaccharide. What happens when water encounters a glycosidic bond?

Polysaccharides

Polysaccharides can contain a few to a thousand or more monosaccharides. Three are important to the body (Figure 3):

  • Starches are polymers of glucose. They occur in long chains called amylose or branched chains called amylopectin, both of which are stored in plant-based foods and are relatively easy to digest.
  • Glycogen is also a polymer of glucose, but it is stored in the tissues of animals, especially in the muscles and liver. It is not considered a dietary carbohydrate because very little glycogen remains in animal tissues after slaughter however, the human body stores excess glucose as glycogen, again, in the muscles and liver.
  • Cellulose, a polysaccharide that is the primary component of the cell wall of green plants, is the component of plant food referred to as &ldquofiber&rdquo. In humans, cellulose/fiber is not digestible however, dietary fiber has many health benefits. It helps you feel full so you eat less, it promotes a healthy digestive tract, and a diet high in fiber is thought to reduce the risk of heart disease and possibly some forms of cancer.

Figure 3. Three important polysaccharides are starches, glycogen, and fiber.

Functions of Carbohydrates

The body obtains carbohydrates from plant-based foods. Grains, fruits, and legumes and other vegetables provide most of the carbohydrate in the human diet, although lactose is found in dairy products.

Although most body cells can break down other organic compounds for fuel, all body cells can use glucose. Moreover, nerve cells (neurons) in the brain, spinal cord, and through the peripheral nervous system, as well as red blood cells, can use only glucose for fuel. In the breakdown of glucose for energy, molecules of adenosine triphosphate, better known as ATP, are produced. Adenosine triphosphate (ATP) is composed of a ribose sugar, an adenine base, and three phosphate groups. ATP releases free energy when its phosphate bonds are broken, and thus supplies ready energy to the cell. More ATP is produced in the presence of oxygen (O2) than in pathways that do not use oxygen. The overall reaction for the conversion of the energy in glucose to energy stored in ATP can be written:

In addition to being a critical fuel source, carbohydrates are present in very small amounts in cells&rsquo structure. For instance, some carbohydrate molecules bind with proteins to produce glycoproteins, and others combine with lipids to produce glycolipids, both of which are found in the membrane that encloses the contents of body cells.

Lipids

A lipid is one of a highly diverse group of compounds made up mostly of hydrocarbons. The few oxygen atoms they contain are often at the periphery of the molecule. Their nonpolar hydrocarbons make all lipids hydrophobic. In water, lipids do not form a true solution, but they may form an emulsion, which is the term for a mixture of solutions that do not mix well.

Triglycerides

A triglyceride is one of the most common dietary lipid groups, and the type found most abundantly in body tissues. This compound, which is commonly referred to as a fat, is formed from the synthesis of two types of molecules (Figure 4):

  • A glycerol backbone at the core of triglycerides, consists of three carbon atoms.
  • Three fatty acids, long chains of hydrocarbons with a carboxyl group and a methyl group at opposite ends, extend from each of the carbons of the glycerol.

Triglycerides

Figure 4: Triglycerides are composed of glycerol attached to three fatty acids via dehydration synthesis. Notice that glycerol gives up a hydrogen atom, and the carboxyl groups on the fatty acids each give up a hydroxyl group.

Triglycerides form via dehydration synthesis. Glycerol gives up hydrogen atoms from its hydroxyl groups at each bond, and the carboxyl group on each fatty acid chain gives up a hydroxyl group. A total of three water molecules are thereby released.

Fatty acid chains that have no double carbon bonds anywhere along their length and therefore contain the maximum number of hydrogen atoms are called saturated fatty acids. These straight, rigid chains pack tightly together and are solid or semi-solid at room temperature (Figure 5a). Butter and lard are examples, as is the fat found on a steak or in your own body. In contrast, fatty acids with one double carbon bond are kinked at that bond (Figure 5b). These monounsaturated fatty acids are therefore unable to pack together tightly, and are liquid at room temperature. Polyunsaturated fatty acids contain two or more double carbon bonds, and are also liquid at room temperature. Plant oils such as olive oil typically contain both mono- and polyunsaturated fatty acids.

Fatty Acid Shapes

Figure 5: The level of saturation of a fatty acid affects its shape. (a) Saturated fatty acid chains are straight. (b) Unsaturated fatty acid chains are kinked.

Whereas a diet high in saturated fatty acids increases the risk of heart disease, a diet high in unsaturated fatty acids is thought to reduce the risk. This is especially true for the omega-3 unsaturated fatty acids found in cold-water fish such as salmon. These fatty acids have their first double carbon bond at the third hydrocarbon from the methyl group (referred to as the omega end of the molecule).

Finally, trans fatty acids found in some processed foods, including some stick and tub margarines, are thought to be even more harmful to the heart and blood vessels than saturated fatty acids. Trans fats are created from unsaturated fatty acids (such as corn oil) when chemically treated to produce partially hydrogenated fats.

As a group, triglycerides are a major fuel source for the body. When you are resting or asleep, a majority of the energy used to keep you alive is derived from triglycerides stored in your fat (adipose) tissues. Triglycerides also fuel long, slow physical activity such as gardening or hiking, and contribute a modest percentage of energy for vigorous physical activity. Dietary fat also assists the absorption and transport of the nonpolar fat-soluble vitamins A, D, E, and K. Additionally, stored body fat protects and cushions the body&rsquos bones and internal organs, and acts as insulation to retain body heat.

Fatty acids are also components of glycolipids, which are sugar-fat compounds found in the cell membrane. Lipoproteins are compounds in which the hydrophobic triglycerides are packaged in protein envelopes for transport in body fluids.

Phospholipids

As its name suggests, a phospholipid is a bond between the glycerol component of a lipid and a phosphorous molecule. In fact, phospholipids are similar in structure to triglycerides. However, instead of having three fatty acids, a phospholipid is generated from a diglyceride, a glycerol with just two fatty acid chains (Figure 6). The third binding site on the glycerol is taken up by the phosphate group, which in turn is attached to a polar &ldquohead&rdquo region of the molecule. Recall that triglycerides are nonpolar and hydrophobic. This still holds for the fatty acid portion of a phospholipid compound. However, the phosphate-containing group at the head of the compound is polar and thereby hydrophilic. In other words, one end of the molecule can interact with oil, and the other end with water. This makes phospholipids ideal emulsifiers, compounds that help disperse fats in aqueous liquids, and enables them to interact with both the watery interior of cells and the watery solution outside of cells as components of the cell membrane.

Other Important Lipids

Figure 6: (a) Phospholipids are composed of two fatty acids, glycerol, and a phosphate group. (b) Sterols are ring-shaped lipids. Shown here is cholesterol. (c) Prostaglandins are derived from unsaturated fatty acids. Prostaglandin E2 (PGE2) includes hydroxyl and carboxyl groups.

A steroid compound (referred to as a sterol) has as its foundation a set of four hydrocarbon rings bonded to a variety of other atoms and molecules (see Figure 6b). Although both plants and animals synthesize sterols, the type that makes the most important contribution to human structure and function is cholesterol, which is synthesized by the liver in humans and animals and is also present in most animal-based foods. Like other lipids, cholesterol&rsquos hydrocarbons make it hydrophobic however, it has a polar hydroxyl head that is hydrophilic. Cholesterol is an important component of bile acids, compounds that help emulsify dietary fats. In fact, the word root chole&ndash refers to bile. Cholesterol is also a building block of many hormones, signaling molecules that the body releases to regulate processes at distant sites. Finally, like phospholipids, cholesterol molecules are found in the cell membrane, where their hydrophobic and hydrophilic regions help regulate the flow of substances into and out of the cell.

Prostaglandins

Like a hormone, a prostaglandin is one of a group of signaling molecules, but prostaglandins are derived from unsaturated fatty acids (see Figure 6c). One reason that the omega-3 fatty acids found in fish are beneficial is that they stimulate the production of certain prostaglandins that help regulate aspects of blood pressure and inflammation, and thereby reduce the risk for heart disease. Prostaglandins also sensitize nerves to pain. One class of pain-relieving medications called nonsteroidal anti-inflammatory drugs (NSAIDs) works by reducing the effects of prostaglandins.

You might associate proteins with muscle tissue, but in fact, proteins are critical components of all tissues and organs. A protein is an organic molecule composed of amino acids linked by peptide bonds. Proteins include the keratin in the epidermis of skin that protects underlying tissues, the collagen found in the dermis of skin, in bones, and in the meninges that cover the brain and spinal cord. Proteins are also components of many of the body&rsquos functional chemicals, including digestive enzymes in the digestive tract, antibodies, the neurotransmitters that neurons use to communicate with other cells, and the peptide-based hormones that regulate certain body functions (for instance, growth hormone). While carbohydrates and lipids are composed of hydrocarbons and oxygen, all proteins also contain nitrogen (N), and many contain sulfur (S), in addition to carbon, hydrogen, and oxygen.

Microstructure of Proteins

Proteins are polymers made up of nitrogen-containing monomers called amino acids. An amino acid is a molecule composed of an amino group and a carboxyl group, together with a variable side chain. Just 20 different amino acids contribute to nearly all of the thousands of different proteins important in human structure and function. Body proteins contain a unique combination of a few dozen to a few hundred of these 20 amino acid monomers. All 20 of these amino acids share a similar structure (Figure 7). All consist of a central carbon atom to which the following are bonded:

  • a hydrogen atom
  • an alkaline (basic) amino group NH2 (see Table 1)
  • an acidic carboxyl group COOH (see Table 1)
  • a variable group

Structure of an Amino Acid

Notice that all amino acids contain both an acid (the carboxyl group) and a base (the amino group) (amine = &ldquonitrogen-containing&rdquo). For this reason, they make excellent buffers, helping the body regulate acid&ndashbase balance. What distinguishes the 20 amino acids from one another is their variable group, which is referred to as a side chain or an R-group. This group can vary in size and can be polar or nonpolar, giving each amino acid its unique characteristics. For example, the side chains of two amino acids&mdashcysteine and methionine&mdashcontain sulfur. Sulfur does not readily participate in hydrogen bonds, whereas all other amino acids do. This variation influences the way that proteins containing cysteine and methionine are assembled.

Amino acids join via dehydration synthesis to form protein polymers (Figure 8). The unique bond holding amino acids together is called a peptide bond. A peptide bond is a covalent bond between two amino acids that forms by dehydration synthesis. A peptide, in fact, is a very short chain of amino acids. Strands containing fewer than about 100 amino acids are generally referred to as polypeptides rather than proteins.

The body is able to synthesize most of the amino acids from components of other molecules however, nine cannot be synthesized and have to be consumed in the diet. These are known as the essential amino acids.

Free amino acids available for protein construction are said to reside in the amino acid pool within cells. Structures within cells use these amino acids when assembling proteins. If a particular essential amino acid is not available in sufficient quantities in the amino acid pool, however, synthesis of proteins containing it can slow or even cease.

Peptide Bond

Figure 8: Different amino acids join together to form peptides, polypeptides, or proteins via dehydration synthesis. The bonds between the amino acids are peptide bonds.

Shape of Proteins

Just as a fork cannot be used to eat soup and a spoon cannot be used to spear meat, a protein&rsquos shape is essential to its function. A protein&rsquos shape is determined, most fundamentally, by the sequence of amino acids of which it is made (Figure 9a). The sequence is called the primary structure of the protein.

The Shape of Proteins

Figure 9: (a) The primary structure is the sequence of amino acids that make up the polypeptide chain. (b) The secondary structure, which can take the form of an alpha-helix or a beta-pleated sheet, is maintained by hydrogen bonds between amino acids in different regions of the original polypeptide strand. (c) The tertiary structure occurs as a result of further folding and bonding of the secondary structure. (d) The quaternary structure occurs as a result of interactions between two or more tertiary subunits. The example shown here is hemoglobin, a protein in red blood cells which transports oxygen to body tissues.

Although some polypeptides exist as linear chains, most are twisted or folded into more complex secondary structures that form when bonding occurs between amino acids with different properties at different regions of the polypeptide. The most common secondary structure is a spiral called an alpha-helix. If you were to take a length of string and simply twist it into a spiral, it would not hold the shape. Similarly, a strand of amino acids could not maintain a stable spiral shape without the help of hydrogen bonds, which create bridges between different regions of the same strand (see Figure 9b). Less commonly, a polypeptide chain can form a beta-pleated sheet, in which hydrogen bonds form bridges between different regions of a single polypeptide that has folded back upon itself, or between two or more adjacent polypeptide chains.

The secondary structure of proteins further folds into a compact three-dimensional shape, referred to as the protein&rsquos tertiary structure (see Figure 9c). In this configuration, amino acids that had been very distant in the primary chain can be brought quite close via hydrogen bonds or, in proteins containing cysteine, via disulfide bonds. A disulfide bond is a covalent bond between sulfur atoms in a polypeptide. Often, two or more separate polypeptides bond to form an even larger protein with a quaternary structure (see Figure 9d). The polypeptide subunits forming a quaternary structure can be identical or different. For instance, hemoglobin, the protein found in red blood cells is composed of four tertiary polypeptides, two of which are called alpha chains and two of which are called beta chains.

When they are exposed to extreme heat, acids, bases, and certain other substances, proteins will denature. Denaturation is a change in the structure of a molecule through physical or chemical means. Denatured proteins lose their functional shape and are no longer able to carry out their jobs. An everyday example of protein denaturation is the curdling of milk when acidic lemon juice is added.

The contribution of the shape of a protein to its function can hardly be exaggerated. For example, the long, slender shape of protein strands that make up muscle tissue is essential to their ability to contract (shorten) and relax (lengthen). As another example, bones contain long threads of a protein called collagen that acts as scaffolding upon which bone minerals are deposited. These elongated proteins, called fibrous proteins, are strong and durable and typically hydrophobic.

In contrast, globular proteins are globes or spheres that tend to be highly reactive and are hydrophilic. The hemoglobin proteins packed into red blood cells are an example (see Figure 9d) however, globular proteins are abundant throughout the body, playing critical roles in most body functions. Enzymes, introduced earlier as protein catalysts, are examples of this. The next section takes a closer look at the action of enzymes.

Proteins Function as Enzymes

If you were trying to type a paper, and every time you hit a key on your laptop there was a delay of six or seven minutes before you got a response, you would probably get a new laptop. In a similar way, without enzymes to catalyze chemical reactions, the human body would be nonfunctional. It functions only because enzymes function.

Enzymatic reactions&mdashchemical reactions catalyzed by enzymes&mdashbegin when substrates bind to the enzyme. A substrate is a reactant in an enzymatic reaction. This occurs on regions of the enzyme known as active sites (Figure 10). Any given enzyme catalyzes just one type of chemical reaction. This characteristic, called specificity, is due to the fact that a substrate with a particular shape and electrical charge can bind only to an active site corresponding to that substrate.

Steps in an Enzymatic Reaction

Figure 10: (a) Substrates approach active sites on enzyme. (b) Substrates bind to active sites, producing an enzyme&ndashsubstrate complex. (c) Changes internal to the enzyme&ndashsubstrate complex facilitate interaction of the substrates. (d) Products are released and the enzyme returns to its original form, ready to facilitate another enzymatic reaction.

Binding of a substrate produces an enzyme&ndashsubstrate complex. It is likely that enzymes speed up chemical reactions in part because the enzyme&ndashsubstrate complex undergoes a set of temporary and reversible changes that cause the substrates to be oriented toward each other in an optimal position to facilitate their interaction. This promotes increased reaction speed. The enzyme then releases the product(s), and resumes its original shape. The enzyme is then free to engage in the process again, and will do so as long as substrate remains.

Other Functions of Proteins

Advertisements for protein bars, powders, and shakes all say that protein is important in building, repairing, and maintaining muscle tissue, but the truth is that proteins contribute to all body tissues, from the skin to the brain cells. Also, certain proteins act as hormones, chemical messengers that help regulate body functions, For example, growth hormone is important for skeletal growth, among other roles.

As was noted earlier, the basic and acidic components enable proteins to function as buffers in maintaining acid&ndashbase balance, but they also help regulate fluid&ndashelectrolyte balance. Proteins attract fluid, and a healthy concentration of proteins in the blood, the cells, and the spaces between cells helps ensure a balance of fluids in these various &ldquocompartments.&rdquo Moreover, proteins in the cell membrane help to transport electrolytes in and out of the cell, keeping these ions in a healthy balance. Like lipids, proteins can bind with carbohydrates. They can thereby produce glycoproteins or proteoglycans, both of which have many functions in the body.

The body can use proteins for energy when carbohydrate and fat intake is inadequate, and stores of glycogen and adipose tissue become depleted. However, since there is no storage site for protein except functional tissues, using protein for energy causes tissue breakdown, and results in body wasting.

Nucleotides

T he fourth type of organic compound important to human structure and function are the nucleotides (Figure 11). A nucleotide is one of a class of organic compounds composed of three subunits:

  • one or more phosphate groups
  • a pentose sugar: either deoxyribose or ribose
  • a nitrogen-containing base: adenine, cytosine, guanine, thymine, or uracil

Nucleotides can be assembled into nucleic acids (DNA or RNA) or the energy compound adenosine triphosphate.

Nucleotides

Figure 11: (a) The building blocks of all nucleotides are one or more phosphate groups, a pentose sugar, and a nitrogen-containing base. (b) The nitrogen-containing bases of nucleotides. (c) The two pentose sugars of DNA and RNA.

Nucleic Acids

The nucleic acids differ in their type of pentose sugar. Deoxyribonucleic acid (DNA) is nucleotide that stores genetic information. DNA contains deoxyribose (so-called because it has one less atom of oxygen than ribose) plus one phosphate group and one nitrogen-containing base. The &ldquochoices&rdquo of base for DNA are adenine, cytosine, guanine, and thymine. Ribonucleic acid (RNA) is a ribose-containing nucleotide that helps manifest the genetic code as protein. RNA contains ribose, one phosphate group, and one nitrogen-containing base, but the &ldquochoices&rdquo of base for RNA are adenine, cytosine, guanine, and uracil.

Figure 12: In the DNA double helix, two strands attach via hydrogen bonds between the bases of the component nucleotides.

The nitrogen-containing bases adenine and guanine are classified as purines. A purine is a nitrogen-containing molecule with a double ring structure, which accommodates several nitrogen atoms. The bases cytosine, thymine (found in DNA only) and uracil (found in RNA only) are pyramidines. A pyramidine is a nitrogen-containing base with a single ring structure

Bonds formed by dehydration synthesis between the pentose sugar of one nucleic acid monomer and the phosphate group of another form a &ldquobackbone,&rdquo from which the components&rsquo nitrogen-containing bases protrude. In DNA, two such backbones attach at their protruding bases via hydrogen bonds. These twist to form a shape known as a double helix (Figure 12). The sequence of nitrogen-containing bases within a strand of DNA form the genes that act as a molecular code instructing cells in the assembly of amino acids into proteins. Humans have almost 22,000 genes in their DNA, locked up in the 46 chromosomes inside the nucleus of each cell (except red blood cells which lose their nuclei during development). These genes carry the genetic code to build one&rsquos body, and are unique for each individual except identical twins.

In contrast, RNA consists of a single strand of sugar-phosphate backbone studded with bases. Messenger RNA (mRNA) is created during protein synthesis to carry the genetic instructions from the DNA to the cell&rsquos protein manufacturing plants in the cytoplasm, the ribosomes.

Adenosine Triphosphate

The nucleotide adenosine triphosphate (ATP), is composed of a ribose sugar, an adenine base, and three phosphate groups (Figure 13). ATP is classified as a high energy compound because the two covalent bonds linking its three phosphates store a significant amount of potential energy. In the body, the energy released from these high energy bonds helps fuel the body&rsquos activities, from muscle contraction to the transport of substances in and out of cells to anabolic chemical reactions.

Structure of Adenosine Triphosphate (ATP)

When a phosphate group is cleaved from ATP, the products are adenosine diphosphate (ADP) and inorganic phosphate (Pi). This hydrolysis reaction can be written:

Removal of a second phosphate leaves adenosine monophosphate (AMP) and two phosphate groups. Again, these reactions also liberate the energy that had been stored in the phosphate-phosphate bonds. They are reversible, too, as when ADP undergoes phosphorylation. Phosphorylation is the addition of a phosphate group to an organic compound, in this case, resulting in ATP. In such cases, the same level of energy that had been released during hydrolysis must be reinvested to power dehydration synthesis.

Cells can also transfer a phosphate group from ATP to another organic compound. For example, when glucose first enters a cell, a phosphate group is transferred from ATP, forming glucose phosphate (C6H12O6&mdashP) and ADP. Once glucose is phosphorylated in this way, it can be stored as glycogen or metabolized for immediate energy.

Chapter Review

Organic compounds essential to human functioning include carbohydrates, lipids, proteins, and nucleotides. These compounds are said to be organic because they contain both carbon and hydrogen. Carbon atoms in organic compounds readily share electrons with hydrogen and other atoms, usually oxygen, and sometimes nitrogen. Carbon atoms also may bond with one or more functional groups such as carboxyls, hydroxyls, aminos, or phosphates. Monomers are single units of organic compounds. They bond by dehydration synthesis to form polymers, which can in turn be broken by hydrolysis.

Carbohydrate compounds provide essential body fuel. Their structural forms include monosaccharides such as glucose, disaccharides such as lactose, and polysaccharides, including starches (polymers of glucose), glycogen (the storage form of glucose), and fiber. All body cells can use glucose for fuel. It is converted via an oxidation-reduction reaction to ATP.

Lipids are hydrophobic compounds that provide body fuel and are important components of many biological compounds. Triglycerides are the most abundant lipid in the body, and are composed of a glycerol backbone attached to three fatty acid chains. Phospholipids are compounds composed of a diglyceride with a phosphate group attached at the molecule&rsquos head. The result is a molecule with polar and nonpolar regions. Steroids are lipids formed of four hydrocarbon rings. The most important is cholesterol. Prostaglandins are signaling molecules derived from unsaturated fatty acids.

Proteins are critical components of all body tissues. They are made up of monomers called amino acids, which contain nitrogen, joined by peptide bonds. Protein shape is critical to its function. Most body proteins are globular. An example is enzymes, which catalyze chemical reactions.

Nucleotides are compounds with three building blocks: one or more phosphate groups, a pentose sugar, and a nitrogen-containing base. DNA and RNA are nucleic acids that function in protein synthesis. ATP is the body&rsquos fundamental molecule of energy transfer. Removal or addition of phosphates releases or invests energy.



Comments:

  1. Acharya

    In my opinion, the topic is very interesting. I suggest you discuss it here or in PM.

  2. Marr

    already saw

  3. Kieron

    You said it right :)

  4. Mongo

    I apologise, but, in my opinion, you are not right. I am assured. I can prove it. Write to me in PM, we will discuss.

  5. Sheffield

    They are similar to the expert)))

  6. Tadhg

    Words of wisdom! RESPECT !!!



Write a message