Amino acid, decarboxylation metabolism, vitamin

The terminology vitamin Bg covers a number of structurally related compounds, including pyridoxal and pyridoxamine and their 5 -phosphates. Pyridoxal 5 -phosphate (PLP), in particular, acts as a coenzyme for a large number of important enzymic reactions, especially those involved in amino acid metabolism. We shall meet some of these in more detail later, e.g. transamination (see Section 15.6) and amino acid decarboxylation (see Section 15.7), but it is worth noting at this point that the biological role of PLP is absolutely dependent upon imine formation and hydrolysis. Vitamin Bg deficiency may lead to anaemia, weakness, eye, mouth, and nose lesions, and neurological changes. 

Certain amino acids and their derivatives, although not found in proteins, nonetheless are biochemically important. A few of the more notable examples are shown in Figure 4.5. y-Aminobutyric acid, or GABA, is produced by the decarboxylation of glutamic acid and is a potent neurotransmitter. Histamine, which is synthesized by decarboxylation of histidine, and serotonin, which is derived from tryptophan, similarly function as neurotransmitters and regulators. /3-Alanine is found in nature in the peptides carnosine and anserine and is a component of pantothenic acid (a vitamin), which is a part of coenzyme A. Epinephrine (also known as adrenaline), derived from tyrosine, is an important hormone. Penicillamine is a constituent of the penicillin antibiotics. Ornithine, betaine, homocysteine, and homoserine are important metabolic intermediates. Citrulline is the immediate precursor of arginine. 

Pyridoxal phosphate is a coenzyme for many enzymes involved in amino acid metabolism, especially in transamination and decarboxylation. It is also the cofactor of glycogen phosphorylase, where the phosphate group is catalytically important. In addition, vitamin Bg is important in steroid hormone action where it removes the hormone-receptor complex from DNA binding, terminating the action of the hormones. In vitamin Bg deficiency, this results in increased sensitivity to the actions of low concentrations of estrogens, androgens, cortisol, and vitamin D. 

Vitamin Ba (pyridoxine, pyridoxal, pyridoxamine) like nicotinic acid is a pyridine derivative. Its phosphorylated form is the coenzyme in enzymes that decarboxylate amino acids, e.g., tyrosine, arginine, glycine, glutamic acid, and dihydroxyphenylalanine. Vitamin B participates as coenzyme in various transaminations. It also functions in the conversion of tryptophan to nicotinic acid and amide. It is generally concerned with protein metabolism, e.g., the vitamin B8 requirement is increased in rats during increased protein intake. Vitamin B6 is also involved in the formation of unsaturated fatty acids. 

The active form of vitamin Be, pyridoxai phosphate, is the most important coenzyme in the amino acid metabolism (see p. 106). Almost all conversion reactions involving amino acids require pyridoxal phosphate, including transaminations, decarboxylations, dehydrogenations, etc. Glycogen phosphory-lase, the enzyme for glycogen degradation, also contains pyridoxal phosphate as a cofactor. Vitamin Be deficiency is rare. 

Pyridoxal phosphate is the coenzyme for the enzymic processes of transamination, racemization and decarboxylation of amino-acids, and for several other processes, such as the dehydration of serine and the synthesis of tryptophan that involve amino-acids (Braunstein, 1960). Pyridoxal itself is one of the three active forms of vitamin B6 (Rosenberg, 1945), and its biochemistry was established by 1939, in considerable part by the work of A. E. Braunstein and coworkers in Moscow (Braunstein and Kritzmann, 1947a,b,c Konikova et al 1947). Further, the requirement for the coenzyme by many of the enzymes of amino-acid metabolism had been confirmed by 1945. In addition, at that time, E. E. Snell demonstrated a model reaction (1) for transamination between pyridoxal [1] and glutamic acid, work which certainly carried with it the implication of mechanism (Snell, 1945). 

Thiamine, biotin and pyridoxine (vitamin B) coenzymes are grouped together because they catalyze similar phenomena, i.e., the removal of a carboxyl group, COOH, from a metabolite. However, each requires different specific circumstances. Thiamine coenzyme decarboxylates only alpha-keto acids, is frequently accompanied by dehydrogenation, and is mainly associated with carbohydrate metabolism. Biotin enzymes do not require the alpha-keto configuration, are readily reversible, and are concerned primarily with lipid metabolism. Pyridoxine coenzymes perform nonoxidative decarboxylation and are closely allied with amino acid metabolism. 

Several of the B vitamins function as coenzymes or as precursors of coenzymes some of these have been mentioned previously. Nicotinamide adenine dinucleotide (NAD) which, in conjunction with the enzyme alcohol dehydrogenase, oxidizes ethanol to ethanal (Section 15-6C), also is the oxidant in the citric acid cycle (Section 20-10B). The precursor to NAD is the B vitamin, niacin or nicotinic acid (Section 23-2). Riboflavin (vitamin B2) is a precursor of flavin adenine nucleotide FAD, a coenzyme in redox processes rather like NAD (Section 15-6C). Another example of a coenzyme is pyri-doxal (vitamin B6), mentioned in connection with the deamination and decarboxylation of amino acids (Section 25-5C). Yet another is coenzyme A (CoASH), which is essential for metabolism and biosynthesis (Sections 18-8F, 20-10B, and 30-5A). 

Vitamins, cofactors, and metals have the potential to broaden the scope of antibody catalysis considerably. In addition to hydrolytic and redox reactions, they facilitate many complex functional group interconversions in natural enzymes.131 Pyridoxal, for example, plays a central role in amino acid metabolism. Among the reactions it makes possible are transaminations, decarboxylations, racemizations, and (3,y-eliminations. It is also essential for ethylene biosynthesis. Not surprisingly, then, several groups have sought to incorporate pyridoxal derivatives into antibody combining sites. 

Vitamin Be has a central role in the metabolism of amino acids in transaminase reactions (and hence the interconversion and catabolism of amino acids and the synthesis of nonessential amino acids), in decarboxylation to yield biologically active amines, and in a variety of elimination and replacement reactions. It is also the cofactor for glycogen phosphorylase and a variety of other enzymes. In addition, pyridoxal phosphate, the metabolically active vitamer, has a role in the modulation of steroid hormone action and the regulation of gene expression. 

Thiamine pyrophosphate has two important coenzyme roles, both of which focus mostly on carbohydrate metabolism (Figs. 8.26 and 8.27). The active portion of the coen- rae is the thiazole ring. The first step in the oxidative decarboxylation of a-keto acids requires TPP. The two most common examples are pyruvate and a-ketoglutarate, oxidatively decarboxyatedto acetyl CoA and succinyl CoA, respectively. The same reaction is found in the metabolism of the branched-chain amino acids valine, isoleucine, leucine, and methionine. In all cases, TPP is a coenzyme in a mitochondrial multienzyme complex, consisting of TPP, lipoic acid, coenzyme A, FAD, and NAD. Note the number of vitamins required for the oxidative decarboxylation of a-keto acids thiamine (TPP), pantothenic acid (coenzyme A), riboflavin (FAD),and niacin (NAD). 

Vitamin Be deficiency symptoms include dermatitis, a microcytic, hypochromic anemia, weakness, irritability, and, in some cases, convulsions. Xanthurenic acid (a degradation product of tryptophan) and other compounds appear in the urine because of an inability to completely metabolize amino acids. A decreased ability to synthesize heme from glycine may cause the microcytic anemia (see Chapter 44), and decreased decarboxylation of amino acids to form neurotransmitters (see Chapter 48) may explain the convulsions. 

Most of the vitamins and cofactors discussed in previous chapters of the text would be needed during starvation because many of the essential metabolic pathways must continue to operate. Among the most obvious vitamins needed for those pathways are pyri-doxal phosphate (for the transamination of amino acids), niacin and riboflavin (for electron transport), thiamin (for the oxidative decarboxylation of pyruvate, a-ketoglu-tarate, and the branched-chain amino acids), biotin (for the carboxylation of pyruvate), and cobalamin (for the conversion of methylmalonyl Co A to succinyl Co A). 

The vitamin Be group of coenzymes consists of pyridoxine, pyridoxal, and pyridoxamine and their metabolically active phosphorylated forms. They are striking for the variety of enzymic reactions in which they are important, and many amino acid transformations, including various transaminations and decarboxylations, are vitamin B dependent. Compounds with vitamin B activity are apparently not stored in the body in large amounts, and biochemical evidence of B deficiency can develop quickly if intake is inadequate (S4). 

Decarboxylation and transamination proceed via the intermediacy of an amino acid-pyridoxal phosphate complex. Pyridoxal phosphate is related to vitamin Be and is of pivotal importance in amino acid metabolism. This cofactor occurs in two forms pyridoxal-5 -phosphate (aldehyde form) and pyridoxamine (amine form), which mediate a reversible interconversion of a-amino acid and a-keto acids via a Schiff-... 

Vitamin is pyridoxal (ll.lOSf), pyridoxine (ll.lOSg) or pyridoxamine (ll.lOSh), all of which exist as their phosphate esters. This vitamin was first isolated in 1936. Pyridoxyl phosphate (ll.lOSi) is a versatile coenzyme used by all living organisms which participates in transamination (11.111) and (11.112), decarboxylation (11.113) and racemisation (11.114) reactions. It is the essential cofactor in amino acid metabolism. Virtually all enzymes which catalyse reactions of 2-amino acids utilise pyridoxyl phosphate as the coenzyme (11.111) through (11.114). 

In the tissues, vitamin Be occurs predominantly as the phosphate of pyridoxal or pyridoxamine, especially the former, except in the liver. Pyri-doxal phosphate functions as a coenzyme in four types of reactions decarboxylation of amino acids, transamination, and the synthesis and cleavage of tryptophan (Chapter 19). This coenzyme is necessary for the deamination of amino acids and for the formation of urea nitrogen. It appears to be essential for the conversion of tryptophan to the pyridine coenzymes. Pyridoxine may be related to fatty acid metabolism and seems to be necessary for normal adrenal cortical function. ... 

Vitamin Bg has a central role in amino acid metabolism as the coenzyme for a variety of reactions, including transamination and decarboxylation. It is also the coenzyme of glycogen phosphorylase and acts to modulate the activity of steroid and other hormones (including retinoids and vitamin D) that act by regulation of gene expression. 

This vitamin acts as a coenzyme in the metabolism of carbohydrates and is present in all living tissues. It acts in the form of thiamin diphosphate in the decarboxylation of a-keto acids and is referred to as cocarboxylase. Thiamin is available in the form of its chloride or nitrate, and its structural formula is shown in Figure 9-12. The molecule contains two basic nitrogen atoms one is in the primary amino group, the other in the quater-... 

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