Amino acids interconversions

An example of an amino acid interconversion that has pathological significance is the hydroxylation of phenylalanine to form tyrosine in the liver (Figure 6.4). 

It acts by inhibiting dihydrofolate reductase. It inhibits conversion of dihydrofolic acid to tetrahydrofolic which is essential for purine synthesis and amino acid interconversions. It primarily affects DNA synthesis but also RNA and protein synthesis. It has cell cycle specific action and kills cells in S phase. It is readily absorbed from gastrointestinal tract but larger doses are absorbed incompletely, little drug is metabolised and it is excreted largely unchanged in urine. 

Amino acids. Glutamate (along with aspartate) is a key substrate and product in transamination (aminotransferase) reactions for amino acid interconversions. Aminotransferases carry out the general reaction ... 

AMINO ACID INTERCONVERSIONS Little is known of the precise amino acid requirements of cestodes. Presumably, most, if not all, their required amino acids can be provided by the host and, as discussed above, cestodes have developed numerous transport systems to acquire these compounds. However, cestodes appear to have a limited ability to catabolise amino acids. This is exemplified by H. diminuta, which has been shown (918) to generate significant 14C02 only from relabelled aspartate and, to a lesser extent, alanine during incubation in vitro with 10 different amino acids (Table 6.6). The few amino acids that are catabolised in cestodes participate in two main pathways, namely transamination and oxidative deamination. 

Ingested protein is digested in a stepwise fashion in the stomach, small intestinal lumen, and small intestinal mucosal cells (Chapter 12). Peptides formed in the intestinal lumen are absorbed into the mucosal cells and degraded to free amino acids. The outflow of amino acids to the portal vein does not reflect the amino acid composition of the ingested protein. Thus, alanine levels increase two-to fourfold, and glutamine, glutamate, and aspartate are absent. These changes arise from amino acid interconversions within the intestinal cell. 

Amino acid metaboli.sm following dietary protein intake. Digestion of protein produces amino acids. Within the intestinal cell, amino acid interconversions form alanine, which is delivered by the portal blood to liver, where it serves as the source of cr-amino nitrogen and pyruvate, which is converted to lipid and glucose. Excess nitrogen is converted to urea. Branched-chain amino acids (BCAAs) are not taken up by the liver but enter peripheral tissues such as muscle where they serve as an important fuel source. Their a-amino nitrogen is transported to liver in the form of alanine. 

It is hardly surprising then that for many years now the study of the behaviour of such slices has continued to provide a goldmine of useful information. The detailed mechanisms of glucose breakdown, amino acid interconversions, and fatty acid synthesis have been resolved in slice preparations. And, more and more, it is becoming possible to use them to tackle much more general problems of the regulation and control of the whole pattern of cell... 

Pyridoxal phosphate is a cofactor required for several reactions involving amino acid interconversion. Its requirement is increased in relation to the amount of protein in the diet. Some of the deficiency symptoms can be readily correlated with their coenzyme function. Thiamin pyrophosphate is a cofactor for pyruvate dehydrogenase, the activity of which is decreased in the brain as a result of deficiency. Pantothenic acid is required not only for... 

Folates Folates are foUc acid derivatives that are naturally present in foods. FoUc acid is the chemically synthesized form of folate. Folates are involved in many metaboUc pathways such as DNA and RNA biosynthesis, repair and methylation, and amino acid interconversions. These compounds possess antioxidant competence that protects the genome by preventing free radical attack [238]. In humans, folate deficiency is associated with a variety of disorders such as coronary heart disease, osteoporosis, Alzheimer s disease, and increased risk of breast and colorectal cancer [239]. 

Enzymatic mechanisms dealing with the 5-amino group of ornithine, -amino group of lysine, indole-nitrogen of tryptophan, and the imidazole-nitrogen of histidine have not as yet been sufficiently well studied. Some reference to the fate of these nitrogen moieties will be made in the discussion of amino acid interconversions (see the chapters. Carbon Catabolism of Amino Acids, and Synthetic Processes InvolAung Amino Acids). 

Folate coenz3nnes carrying single carbon units in different states of reduction participate in a variety of reactions in which methyl groups are transferred (Figure 1.). These reactions include 1) formation of the purine ring 2) amino acid interconversions ... 

In summary, the biochemical function of folate coenzymes is to transfer and use these one-carbon units in a variety of essential reactions (Figure 2), including de novo purine biosynthesis (formylation of glycinamide ribonucleotide and 5-amino-4-imidazole carboxamide ribonucleotide), pyrimidine nucleotide biosynthesis (methylation of deoxyuridylic acid to thy-midylic acid), amino-acid interconversions (the interconversion of serine to glycine, catabolism of histidine to glutamic acid, and conversion of homocysteine to methionine (which also requires vitamin B12)), and the generation and use of formate. 

This thiol-disulfide interconversion is a key part of numerous biological processes. WeTJ see in Chapter 26, for instance, that disulfide formation is involved in defining the structure and three-dimensional conformations of proteins, where disulfide "bridges" often form cross-links between q steine amino acid units in the protein chains. Disulfide formation is also involved in the process by which cells protect themselves from oxidative degradation. A cellular component called glutathione removes potentially harmful oxidants and is itself oxidized to glutathione disulfide in the process. Reduction back to the thiol requires the coenzyme flavin adenine dinucleotide (reduced), abbreviated FADH2. 

The citric acid cycle is the final common pathway for the aerobic oxidation of carbohydrate, lipid, and protein because glucose, fatty acids, and most amino acids are metabolized to acetyl-CoA or intermediates of the cycle. It also has a central role in gluconeogenesis, lipogenesis, and interconversion of amino acids. Many of these processes occur in most tissues, but the hver is the only tissue in which all occur to a significant extent. The repercussions are therefore profound when, for example, large numbers of hepatic cells are damaged as in acute hepatitis or replaced by connective tissue (as in cirrhosis). Very few, if any, genetic abnormalities of citric acid cycle enzymes have been reported such ab-normahties would be incompatible with life or normal development. 

The citric acid cycle is not only a pathway for oxidation of two-carbon units—it is also a major pathway for interconversion of metabolites arising from transamination and deamination of amino acids. It also provides the substtates for amino acid synthesis by transamination, as well as for gluconeogenesis and fatty acid synthesis. Because it fimctions in both oxidative and synthetic processes, it is amphibolic (Figure 16—4). 

The citric acid cycle is amphibolic, since in addition to oxidation it is important in the provision of carbon skeletons for gluconeogenesis, fatty acid synthesis, and interconversion of amino acids. 

Further complications may arise with the larger amino acids such as isoleucine, where the R side-chain itself contains a chiral carbon atom [R = CH3CH2C H(CH)3, where the asterisk denotes the second chiral centre]. This molecule is an example of a diastereomer - a molecule with more than one chiral centre. Diastereomers have different physical and chemical properties, and their interconversion is more complicated, and is termed epimerization. 

The interconversion of fructose-6-phosphate and fructose-1,6 bis phosphate is a control point in glycolysis and gluconeogenesis. Gluconeogenesis is a pathway which allows carbon atoms from substrates such as lactate, glycerol and some amino acids to be used for the synthesis of glucose, so it is in effect physiologically the opposite of... 

These one-carbon groups, which are required for the synthesis of purines, thymidine nucleotides and for the interconversion some amino acids, are attached to THF at nitrogen-5 (N5), nitrogen-10 (N10) or both N5and N10. Active forms of folate are derived metabolically from THF so a deficiency of the parent compound will affect a number of pathways which use any form of THF. 

In addition to the common pathways, glycolysis and the TCA cycle, the liver is involved with the pentose phosphate pathway regulation of blood glucose concentration via glycogen turnover and gluconeogenesis interconversion of monosaccharides lipid syntheses lipoprotein formation ketogenesis bile acid and bile salt formation phase I and phase II reactions for detoxification of waste compounds haem synthesis and degradation synthesis of non-essential amino acids and urea synthesis. 

Humans have a limited capacity to synthesize amino acids de novo, but extensive interconversions can occur. Those amino acids which cannot be formed within the body and must be supplied by the diet are called essential . Members of this group, which includes the branched chain amino acids leucine and valine, and also methionine and phenylalanine, are all dietary requirements. Such essential amino acids may be chemically converted, mainly in the liver, into the non-essential amino acids. The term non-essential does not equate with not biochemically important but simply means they are not strict dietary components. 

This rotamer model for the fluorescence decay of an aromatic amino acid also predicts that the amplitudes of the kinetic components should correspond to the ground-state rotamer populations, provided that interconversion... 

Fig. 6.4 Reversible interconversion of amino acid and keto acid. Conjugation of the imine bond in the aldimine with the electron sink of the pyridine ring plus protonation of the pyridine nitrogen as well as the metal ion - all this results in weakening of the C-H bond of the amino acid residue. Thus, also catalyzed is a-proton exchange, racemization of a chiral center at the a-carbon atom and decarboxylation of the appropriate amino acid. ...

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