Amino Acids: Key Points Useful for CSIR Exam

          Amino acids are the monomeric units, or building blocks of proteins joined by a particular sort of covalent linkage. The properties of proteins rely upon the characteristic grouping of part amino acids, every one of which has particular side chains. 

          Amino corrosive polymerization requires end of a water particle as the carboxyl group of one amino corrosive responds with the amino group of another amino corrosive to shape a covalent amide bond. The redundancy of this procedure with numerous amino acids yields a polymer, known as a polypeptide. The amide bonds connecting amino acids to one another are known as peptide bonds.     Every amino corrosive unit inside the polypeptide is alluded to as a buildup. The succession of amino acids in a protein is managed by the arrangement of nucleotides in a portion of the DNA in the chromosomes and the uniqueness of each living being is because of its enrichment of explicit proteins.

Structure:

• The majority of the normally happening amino acids in proteins are L- amino acids. 
• The key 20 amino acids in proteins have an amino group, a carboxyl group, a hydrogen molecule, and an R-group joined to the α-carbon. 
• Proline is a special case since it has a cyclic structure and contains an optional amine group (called an imino group) rather than an essential amine group (called an amino group). 
• Amino acids are ordered by the concoction properties of the R-group. Except for glycine (R = H), the amino acids have no less than one assymetric carbon particle (the α-carbon). 
• The supreme arrangement of the four groups joined to the a-carbon is ordinarily contrasted with the setup of L-glyceraldehyde. 
• The D and L assignments determine outright setup and not the dextro (right) or levo (left) course of revolution of plane polarized light by the deviated carbon focus. 
• In natural science, the task of total designs of a deviated focus is made by the R and S grouping of isomers. This framework organizes the substituents connected to the deviated carbon molecule and the task depends on the clockwise (R) or the counterclockwise (S) situating of the three higher need groups.

Classification:

A useful classification of the amino acids is based on the solubility characteristics of the side chains. The R-groups fall into four classes:

1. Nonpolar (hydrophobic),
2. Polar, negatively charged (acidic),
3. Polar, positively charged (basic), and
4. Polar, neutral (un-ionized)

Nonpolar Amino Acids:

Glycine:

• Glycine is the smallest amino acid and has an hydrogen atom as its R-group. 
• It is the only α -amino acid that is optically inactive. 
• The small R-group gives a minimum of steric hindrance to rotation about bonds. Consequently, glycine fits into crowded regions of many peptide chains. 
• Collagen, a rotationally restricted fibrous protein, has glycyl residues in about every third position in its polypeptide chains. 
• Glycine is used for the biosynthesis of many nonprotein compounds, such as porphyrins and purine. Glycine helps in lipid absoption. Glycine acts as neurotransmitter. 
• Nonketotic hyperglycinemia (NKH) is an inborn error of glycine degradation in which a large amount of glycine accumulates throughout the body.

Alanine:

The side chain of amino acid alanine is a methyl group. Other amino acids might be considered to be chemical derivatives of alanine, with substituents on the β-carbon. Alanine and glutamic acid provide links between amino acid and carbohydrate metabolism.

Alanine

Valine, Leucine, and Isoleucine:

• These branched-chain aliphatic amino acids contain bulky nonpolar R-groups and involve in hydrophobic interactions. These three are essential amino acids. 
• A defect in these amino acid catabolism leads to maple syrup urine disease.  
• Ile contain asymmetrical centers at both the α- and β-carbons and four stereoisomers, only one of which occurs in protein. 
• The bulky side chains tend to join in the interior of water-soluble globular proteins. Thus, the hydrophobic amino acid residues stabilize the 3D structure of the polymer.

Valine

Isoleucine

Phenylalanine:

• A planar hydrophobic phenyl ring is part of the R-group of phe(Phenyl alanine). 
• It is an essential amino acid whose metabolic conversion to tyrosine is defective in phenylketonuria condition. Phenylalanine, tyrosine, and tryptophan are the only α-amino acids that contain aromatic groups and consequently are the only residues that absorb ultraviolet light. 
• Tryptophan and tyrosine absorb significantly more energy than phenylalanine at 280 nm, the wavelength commonly used to measure the concentration of protein in a solution.

Phenylalanine

Tryptophan:

• A bicyclic nitrogenous aromatic ring system (an indole ring) is attached to the β-carbon of alanine to form the R-group of tryptophan. 
• Tryptophan is a precursor of serotonin, melatonin, nicotinamide etc. It is an essential amino acid. 
• The indole group of tryptophan absorbs UV light at 280 nm, a property that is useful for spectrophotometric measurement of protein concentration. 
• Tryptophan and tyrosine both show fluorescence; however, tryptophan absorbs more intensely. 
• When molecules are raised to a higher energy state by absorption of radiant energy, they generally are unstable and return to the ground state. 
• The energy released in this process manifests as heat or light. 
• The process of light emission is called as fluorescence. The quantum of energy released as fluorescence is always less than that of absorbed energy. Thus, the fluorescent light always appears at a longer wavelength than the original absorbed light energy. 
• Tryptophan fluorescence studies can provide useful information regarding protein and protein-ligand conformations due to the effects of surrounding amino acid residues.

Tryptophan

Methionine:

• This essential amino acid contains side chain as methyl group attached to sulfur. 
• Methionine acts as donor of a methyl group in many transmethylation reactions. For example, in the synthesis of epinephrine, creatine, and melatonin. 
• Most of the sulfur-containing compounds of the body are derived from methionine.

Methionone

Proline:

• Proline contains a secondary amine group instead of Primary amine group which is called an imine. 
• For this reason, proline is called an imino acid. Since the three-carbon side chain of proline is fused to the α-nitrogen group, this compound has a rotationally constrained rigid-ring structure. 
• As a result, prolyl residues in a polypeptide introduce obstacles on the folding of chains. In collagen, certain prolyl residues are hydroxylated. The hydroxylation occurs during synthesis of protein and requires ascorbic acid as a cofactor. Deficiency of vitamin C causes malformation of collagen and scurvy.

Proline

Acidic Amino Acids:

Aspartic Acid:

The β-carboxylic acid group of aspartic acid has a pK' of 3.86 and is ionized at pH 7.0. The anionic carboxylate groups tend to occur on the surface of water-soluble proteins, where they interact with water. Such surface interactions stabilize protein folding.

Aspartic Acid

Glutamic Acid:

• The glutamic acid's γ -carboxylic acid group has a pK' of 4.25 and is ionized at physiological pH. The anionic groups of glutamate tend to occur on the surfaces of proteins in aqueous environments. Glutamate acts as primary excitatory neurotransmitter in the brain. Its levels are regulated by clearance that is mediated by glutamate transfer protein in crucial motor control areas in the CNS. 
• In amyotrophic lateral sclerosis (ALS) glutamate levels are elevated in serum, spinal fluid, and brain; glutamate excitotoxicity is implicated in the progression of the disease. 
• ALS is a progressive disorder affecting motor neurons in the spinal cord, brain stem, and cortex. 
• The precise molecular basis of the disease is unknown; however, factors involved are glutamate excitotoxicity, genetics, oxidative stress, and diminished neurotrophic factors. 
• Residues of γ -carboxyglutamic acid (Gla) bear two negative charges and can strongly bind calcium ions. 
• γ-Carboxylation of glutamic acid residues is a posttranslational modification and requires vitamin K as a cofactor. 
• γ-Carboxyglutamate residues are present in a number of blood coagulation proteins (factors II, VII, IX, and X) and anticoagulant proteins C and S. 
• Osteocalcin, a protein present in the bone, also contains γ-carboxyglutamate residue.

Glutamic Acid

Basic Amino Acids:

Lysine:

• Lysine is an essential amino acid. The long side chain of lysine has a reactive amino group linked to the ε-carbon. 
• The ε-NH2 is protonated at physiological pH. The lysyl side chain of Lysine forms ionic bonds with negatively charged groups of acidic amino acids. 
• The ε-NH2 groups of lysyl residues are covalently linked to biotin, lipoic acid, and retinal and a constituent of visual pigment. 
• In collagen and in some glycoproteins, γ-carbons of some lysyl residues are hydroxylated, and sugar moieties are attached at these sites. 
• In elastin and collagen, some ε-carbons of lysyl residues are oxidized to reactive aldehyde groups, with elimination of NH3. 
• These -CHO groups then react with other ε amino groups to form covalent cross-links between polypeptides, thereby providing tensile strength and insolubility to protein fibers. 
• Examples of cross-linked amino acid residues are desmosine, isodesmosine, lysinonorleucine, hydrolysinonorleucine, merodesmosine, and dehydromerodesmosine. 
• Lysyl side chain groups participate in a different type of cross-linking in the formation of fibrin, a process essential for the clotting of blood. 
• In this reaction, the ε-amino group of one fibrin polypeptide forms a covalent linkage with the glutamyl residue of another fibrin polypeptide.

Lysine

Histidine:

• Histidine contains imidazole group attached to the β-carbon. 
• The pK' value of histidyl residues in protein varies depending on the nature of the neighboring residues. 
• The imidazolium-imidazole buffering pair possess a major role in acid-base regulation. 
• The imidazole group works as a nucleophile, or a general base, in the active sites of numerous enzymes and may bind metal ions. 
• Histidine is nonessential amino acid in adults but is essential in the diet of people with uremia. Decarboxylation of histidine to yield histamine happen in mast cells present in loose connective tissue.
• The numerous specific reactions of histamine are determined by the type of receptor (H1 or H2) present in the target cells. 
• H1 receptors mediate contraction of smooth muscle receptors and antagonized by diphenhydramine and pyrilamine. 
• H1-receptor antagonists are used in the treatment of allergic diseases. 
• H2 receptor mediates secretion of HCl by the stomach and an increase in heart rate.

Arginine:

• Arginine contains positively charged guanidinium group attached to the δ-carbon which is stabilized by resonance between the two amino groups and has a pK' value of 12.48.
•  Arginine is involved in the synthesis of creatine and it participates in the urea cycle. 
• Nitric oxide synthase converted nitrogen of the guanidino group of arginine to nitric oxide.
• NO is unstable, highly reactive, and possess a life span of only a few seconds. However, NO influence many biological activities, including vasodilation, inflammation, and neurotransmission.

Neutral Amino Acids:

Serine:

The primary alcohol group of serine can form esters with phosphoric acids and glycosides with sugars. The phosphorylation and dephosphorylation processes control the biochemical activity of several proteins. Active centers of some enzymes contain seryl hydroxyl groups and can be denatured. The hydroxyl group of serine has a weakly acidic pK' of 13.6.

Threonine:

Threonine is essential amino acid. It has a second asymmetrical carbon atom in the side chain and therefore can have four isomers, only one of which, L-threonine, occurs in proteins. The hydroxyl group participates in reactions with phosphoric acid and with sugar residues.

Cysteine:

• The weakly acidic sulfhydryl group (-SH) of cysteine is essentially intact at physiological pH. 
• Free sulphhydral groups are essential for the function of many enzymes and structural proteins. Heavy metal ions like Pb2+ and Hg2+, inactivate these proteins by binding with their-SH groups.
• Two cysteinyl-sulfhydral groups can be oxidized to form cystine. 
• A covalent disulfide bond of cystine can bind two parts of a single polypeptide chain or two different polypeptide chains via cross-linking of cysteine residues. 
• These - S - S - bonds are crucial both for the folding of polypeptide chains and for the association of polypeptides in proteins that have more than one chain.

Cysteine

Tyrosine:

• The phenolic hydroxyl group of this aromatic amino acid has a weakly acidic pK' of about 10 and consequenty is un-ionized at physiological pH. 
• In some enzymes, the hydrogen of the phenolic hydroxyl group can involve in hydrogen bond formation with oxygen and nitrogen atoms.
• Tyrosine accumulates in tissues and blood in tyrosinosis and tyrosinemia, which are occured because of inherited defects in catabolism of this amino acid. 
• Tyrosine is the biosynthetic precursor of catecholamines, thyroxine, and melanin. 
• Tyrosine and its biosynthetic precursor, phenylalanine, both absorb UV light.

Tyrosine

Asparagine:

The side chain of this amide derivative of aspartic acid has no acidic or basic properties but is polar and participates in hydrogen bond formation. It is cleaved to aspartic acid and ammonia by the enzyme asparaginase. In glycoproteins, the carbohydrate side chain is often linked via the amide group of asparagine.

Glutamine:

• This amide of glutamate has properties similar to those of asparagine. 
• The 7-amido nitrogen, derived from ammonia, can be used in the synthesis of purine and pyrimidine nucleotides converted to urea in the liver or released as NH3 in the kidney tubular epithelial cells. The last reaction, catalyzed by the enzyme glutaminase, functions in acid-base regulation by neutralizing H+ ions in the urine. 
• The most abundant amino acid in the body is Glutamine
• It composes more than 60% of the free amino acid pool in skeletal muscle. 
• It is metabolized in both liver and gut tissues. 
• Glutamine, along with alanine, are significant precursors of glucose production during fasting. 
• It is a nitrogen donor in the synthesis of purines and pyrimidines required for nucleic acid synthesis. Glutamine is enriched in enteral and parenteral nutrition to promote tissue growth; it also enhances immune functions in patients recovering from surgical procedures. 
• Thus, glutamine might be classified as a conditionally essential amino acid during severe trauma and illness.

Unusual Amino Acids:

Several L-amino acids have biological functions as free amino acids rather than as constituents of proteins. Examples are as follows:

1. β-Alanine is part of the vitamin B5.

2. Homocysteine, homoserine, omithine, and citrulline are intermediates in the biosynthesis of certain other amino acids.

3. Taurine, which has an amino group in the β-carbon and a sulfonic acid group instead of COOH, is present in the central nervous system.

4. Gamma-Aminobutyric acid is an inhibitory neurotransmitter.

5. Hypoglycin A is present in unripe akee fruit and produces severe hypoglycemia when taken.

6. Some D-amino acids are found in polypeptide antibiotics, such as gramicidins and bacitracins, and
in bacterial cell wall peptides.

Amino Acids Used as Drugs:

• D-Penicillamine (D- β, β-dimethylglycine), a metabolite of penicillin, was first isolated in the urine specimens from patients treated with penicillin with liver disease. It is a good chelator of metals such as copper, zinc, and lead. It is used in the chelation therapy of Wilson's disease, which is caused by excess copper accumulation leading to hepatolenticular degeneration.
• N -Acetylcysteine is administered in the acetoaminophen toxicity. It replenishes the hepatic stores of glutathione. N-Acetylcysteine is also used in the treatment of pulmonary diseases including cystic fibrosis. In patients with chronic renal insufficiency, prophylactic oral administration of N-Acetylcysteine have been used in the prevention of further renal impairment due to administration of radiographic contrast agents. In this setting presumably N-Acetylcysteine functions as an antioxidant and augments the vasodilatory effect of nitric oxide via the formation of S-nitrosothiol.
• Gabapentin is gamma-aminobutyrate covalently linked to cyclohexane to make it lipophilic and to facilitate its transport across the blood-brain barrier. It is used as an anticonvulsant and in amyotrophic lateral sclerosis.