In this article we will discuss about the Biosynthesis and Catabolism of Amino Acids.
Biosynthesis of Amino Acids:
Plants and bacteria can form all 22 amino acids from amphibolic intermediates. But humans and other animals cannot synthesize some of these. Therefore, these are supplied by the diet and are termed nutritionally essential amino acids. The remainders are synthesized in the body. Therefore, these are termed nutritionally nonessential amino acids.
According to nutritional scientists, the nutritionally essential amino acids are termed “essential” or “indispensable” amino acids and the nutritionally nonessential amino acids are termed “nonessential” or “dispensable” amino acids.
Nutritionally nonessential amino acids are more important to the cell than the nutritionally essential ones. The essential amino acids are methionine, tryptophan, valine, leucine, isoleucine, phenylalanine, threonine, lysine, histidine.
Essential Amino Acids:
Histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. An “essential” or “indispensable” amino acid is defined as one which cannot be synthesized by the organism from substances ordinarily present in the diet at a rate commensurate with certain physiological requirements.
Certain of these essential amino acids are replaced by the corresponding α-keto acids or α-hydroxy acids. Ten amino acids are required for the optimal growth of animals found in the experiments on white rats. But in case of humans, nine essential amino acids are required for the optimal growth of the young and for the maintenance of nitrogen equilibrium in the adult.
These nine essential amino acids are: Histidine, methionine, trytophan, valine, phenylalanine, leucine, isoleucine, threonine and lysine. Two amino acids, arginine and histidine, which are required for animals, are “nutritionally semi-essential” for humans because they may be synthesized in tissues at rates inadequate to support growth of children.
Certain nonessential amino acids in the diet serve as the sparing action of certain essential amino acids, e.g., tyrosine spares phenylalanine and cystine spares methionine. In phenyl ketonuric individuals, who are unable to convert phenylalanine into tyrosine, the latter becomes an essential amino acid.
If a single essential amino acid is omitted from the group and fed separately several hours later, the nutritional effectiveness of the entire group is impaired. The omission of an essential amino acid from the diet results in the negative nitrogen balance or decrease of growth.
Nutritionally Nonessential Amino Acids formed from Amphibolic Intermediates:
Alanine:
Alanine is formed from pyruvate by transamination in presence of the coenzyme pyridoxal phosphate (B6-PO4) in all forms of life.
Glutamic Acid:
In all forms of life, glutamic acid is formed from α-ketoglutarate by glutamate dehydrogenase.
Bacteria contain only an NAD+– dependent dehydrogenase; whereas yeast and fungi contain two glutamate dehydrogenases specific for NAD+ and for NADP+.
It is also to be noted that NAD+ functions in glutamate catabolism and N ADP+ in glutamate biosynthesis in animals.
In many bacteria glutamate is formed by glutamate synthetase which is given in Fig. 20.10.
Aspartic Acid:
Aspartic acid is formed by transamination of oxaloacetate.
Glutamine:
In plants, animals and bacteria, glutamine is synthesized from glutamate by glutamine synthetase. NH4+ aminates glutamate requiring ATP and Mg++ which is shown in Fig. 20.11.
Asparagine:
Asparagine is synthesized from aspartate by asparagine synthetase. ATP and Mg++ are also required in this reaction. ATP is hydrolyzed to AMP + PPi.R-NH2 aminates aspartate which is shown in Fig. 20.12.
Serine:
In mammalian tissues, serine is synthesized from 3-phosphoglycerate, an intermediate of glycolysis, by two pathways. One pathway uses phosphorylated intermediates and the other uses non-phosphorylated intermediates. Majority of the serine is synthesized by the pathway via phosphorylated intermediates. Plants and microorganisms follow this pathway.
Synthesis via Phosphorylated Intermediates:
3-phosphoglycerate is oxidized to phospho-hydroxypyruvate which by transamination is converted to phosphoserine. Finally, phosphoserine is converted to serine by phosphatase.
Synthesis via Non-Phosphorylated Intermediates:
3-phosphoglycerate is dephosphorylated to glycerate by a phosphatase. Glycerate is oxidized to hydroxypyruvate which is finally trans-aminated to form serine. The reactions are shown in Fig. 20.13.
Glycine:
Glycine is synthesized from serine as well as choline as shown in Fig. 20.14.
Nutritionally Nonessential Amino Acids formed from other Nutritionally Nonessential Amino Acids:
Proline:
Proline is synthesized from glutamate by reversal of reactions for proline catabolism.
Hydroxyproline:
Since proline serves as a precursor of hydroxyproline, this is also synthesized from glutamate.
Nutritionally Nonessential Amino Acids formed from Nutritionally Essential Amino Acids:
Cysteine:
Cysteine is formed from methionine (essential amino acid).
Methionine is first converted to homocysteine which is converted to cysteine in conjugation with serine:
Tyrosine:
The conversion of phenylalanine (an essential amino acid) to tyrosine is catalyzed by phenylalanine hydroxylase complex, a mixed function oxygenase present in mammalian liver but absent from other tissues.
One atom of molecular oxygen is incorporated into the para position of phenylalanine and the other atom is reduced forming water (shown in Fig. 20.16). The reducing power, supplied ultimately by NADPH, is immediately provided as tetra-hydro-biopterine, a pteridine resembling that in folic acid. The reaction is not reversible.
Nutritionally Essential Amino Acids:
Nutritionally essential amino acids are synthesized by bacteria but the synthesis does not take place in mammalian tissues; hence the synthesis is not discussed here.
Catabolism of Amino Acids:
List of amino acids converted to carbohydrate and fat or both:
L-amino acids are catabolized to amphibolic intermediates.
Amino Acids Forming Oxaloacetate:
Asparagine and aspartate are converted to oxaloacetate by the successive actions Of asparaginase and a transaminase (shown in Fig. 20.17).
Amino Acids Forming α-ketoglutarate:
Glutamine and glutamate are catabolized like that of asparagine and aspartate but with the formation of α-ketoglutarate (shown in Fig. 20.18.).
Proline is oxidized to a form of dehydroproline which, on addition of water, forms glutamate y-semi-aldehyde. This is then oxidized to glutamate and trans-aminated to α-ketoglutarate (shown in Fig. 20.19).
Arginine and histidine are both converted to α-ketoglutarate. Arginine is converted to ornithine by arginase with the removal of urea. Ornithine, by transamination forms glutamate γ-semi-aldehyde which is oxidized to glutamate and trans-aminated to α-ketoglutarate (shown in Fig. 20.20).
Histidine, on deamination, produces urocanic acid which is converted to 4-imidazolone-5- propionate by urocanase. This product—on addition of water and internal oxidation-reduction—forms glutamate which is trans-aminated to α-ketoglutarate (shown in Fig. 20.21).
Amino Acids Forming Pyruvate:
Glycine is converted to serine by serine hydroxy-methyltransferase. Serine then forms pyruvate by serine dehydratase (shown in Fig. 20.22).
Alanine forms pyruvate by transamination— Fig. 20.23.
Serine is converted to pyruvate by serine dehydratase, a pyridoxal phosphate protein. Addition and loss of water as well as loss of ammonia are involved in this reaction. The reaction is shown in Fig. 20.24.
This conversion of serine to pyruvate is prominent in the liver tissue of rats and guinea-pigs because serine dehydratase is rich in this tissue of these animals.
But in humans and many other vertebrates, serine is degraded to glycine by serine hydroxy-methyltransferase. The further catabolism follows the glycine cleavage system.
Cystine is converted to cysteine by an NADH- dependent cystine reductase as shown in Fig. 20.25.
Cysteine is Converted to Pyruvate by:
1. Transamination and loss of H2S.
2. By oxidation of the sulfhydryl group forming cysteine sulfinic acid, transamination and by desulfination (shown in Fig. 20.26).
Threonine aldolase cleaves threonine to acetaldehyde and glycine. Glycine is catabolized to pyruvate as discussed before. Both pyruvate and acetaldehyde then form acetyl-GoA (shown in Fig. 20.27).
Hydroxyproline is converted to pyruvate and glyoxylate. The conversion is indicated in Fig. 20.28.
