Valine deamination

Free amino acids are further catabolized into several volatile flavor compounds. However, the pathways involved are not fully known. A detailed summary of the various studies on the role of the catabolism of amino acids in cheese flavor development was published by Curtin and McSweeney (2004). Two major pathways have been suggested (1) aminotransferase or lyase activity and (2) deamination or decarboxylation. Aminotransferase activity results in the formation of a-ketoacids and glutamic acid. The a-ketoacids are further degraded to flavor compounds such as hydroxy acids, aldehydes, and carboxylic acids. a-Ketoacids from methionine, branched-chain amino acids (leucine, isoleucine, and valine), or aromatic amino acids (phenylalanine, tyrosine, and tryptophan) serve as the precursors to volatile flavor compounds (Yvon and Rijnen, 2001). Volatile sulfur compounds are primarily formed from methionine. Methanethiol, which at low concentrations, contributes to the characteristic flavor of Cheddar cheese, is formed from the catabolism of methionine (Curtin and McSweeney, 2004 Weimer et al., 1999). Furthermore, bacterial lyases also metabolize methionine to a-ketobutyrate, methanethiol, and ammonia (Tanaka et al., 1985). On catabolism by aminotransferase, aromatic amino acids yield volatile flavor compounds such as benzalde-hyde, phenylacetate, phenylethanol, phenyllactate, etc. Deamination reactions also result in a-ketoacids and ammonia, which add to the flavor of... 

The suggestion of an alternative non-mevalonoid route in monoterpenoid biosynthesis77 has received some support in the efficient incorporation of L-[l/- 4C]valine into the DMAPP moiety of linalool 78 a pathway via deamination to dimethylacrylic acid is proposed. L-Leucine and l-valine are also incorporated, at least in part, into the DMAPP moiety of geraniol (8) and citronellol.79 (lf ,3/ )-Chrysanthemic acid (25) is biosynthesized80 in Chrysanthemum cinerariaefolium from ( R,3R) chrysanthemyl alcohol (26) but not from precursors with the lavandulyl (27) or artemisyl (28) skeletons (Scheme 4) (li ,3R)-chrysanthemyl alcohol (26) has been... 

D-Amino oxidase is a peroxisomal enzyme that catalyzes the oxidative deamination of D-amino acids to give the corresponding a-keto acids, ammonia, and hydrogen peroxide. In this assay, a-ketovaleric acid from D-valine was quantitated. 

Liver plays a major role, since it can oxidize all amino acids except leucine, isoleucine, and valine (see Chapter 22). It also produces the nonessential amino acids from the appropriate carbon precursors. Ammonia formed in the gastrointestinal tract or from various deaminations in the liver is converted to urea and excreted in urine (discussed later). 

Conservation of amino acids filtered at the glomerulus is made possible by the existence of four main transport systems for specific amino acids that facilitate active reabsorption of these amino acids from the proximal tubule. A lack or deficiency of the transport system responsible for the absorption of valine, alanine, cystine, and tryptophan, and of the transport system for arginine, lysine, cystine, and ornithine, leads to excretion of these specific amino acids in urine, which is characterized as renal aminoaciduria to distinguish it from overflow aminoaciduria. In the latter situation, the production of amino acids far exceeds the proximal tubular reabsorption capacity, thus leading to overflow of amino acids into urine. This can occur due to defective metabolism of amino acids, as is the case when phenylalanine cannot be metabolized due to the deficiency of the enzyme phenylalanine hydroxylase, or to the inability to deaminate amino acids in liver disease. 

Aspartase deficiency in Y. pestis is another example of a substantial effect of a single base transversion (in this case a missense mutation) that nevertheless results in 99.99% reduction in enzyme activity [32], AspA activity catalyzes the deamination of L-aspartate to form fumarate, a component of the tricarboxylic acid cycle. Comparison of aspA in Y. pestis and closely related Y. pseudotuberculosis defines only a single base transversion (G.C-T.A) at a.a. position 363. This causes exchange of valine (GUG) in... 

The syntheses of valine, leucine, and isoleucine from pyruvate are illustrated in Figure 14.9. Valine and isoleucine are synthesized in parallel pathways with the same four enzymes. Valine synthesis begins with the condensation of pyruvate with hydroxyethyl-TPP (a decarboxylation product of a pyruvate-thiamine pyrophosphate intermediate) catalyzed by acetohydroxy acid synthase. The a-acetolactate product is then reduced to form a,/3-dihydroxyisovalerate followed by a dehydration to a-ketoisovalerate. Valine is produced in a subsequent transamination reaction. (a-Ketoisovalerate is also a precursor of leucine.) Isoleucine synthesis also involves hydroxyethyl-TPP, which condenses with a-ketobutyrate to form a-aceto-a-hydroxybutyrate. (a-Ketobutyrate is derived from L-threonine in a deamination reaction catalyzed by threonine deaminase.) a,/3-Dihydroxy-/3-methylvalerate, the reduced product of a-aceto-a-hydroxybutyrate, subsequently loses an HzO molecule, thus forming a-keto-/kmethylvalerate. Isoleucine is then produced during a transamination reaction. In the first step of leucine biosynthesis from a-ketoisovalerate, acetyl-CoA donates a two-carbon unit. Leucine is formed after isomerization, reduction, and transamination. 

Amino acid catabohsm is particularly important dining starvation. Because of the mass of muscle, amino acid catabohsm is particularly important in this tissue which, in starvation, supplies the liver with most of its gluconeogenic precursors (see also Fig. 13-11). Amino acids resulting from proteolysis during starvation are interconverted in the muscle so that 60% of the amino acid mass that leaves the muscle is either glutamine or alanine. The branched-chain amino acids valine, leucine, and isoleucine, which are aU essential amino acids, are deaminated in muscle by a specific aminotransferase, and the corresponding 2-oxoacids are transported to the liver for further metabohsm via branched-chain 2-oxoacid dehydrogenase (BCOADH). The aminotransferase is inactive in the hver, and this ensures that the peripheral tissues are supphed with valine, leucine, and isoleucine. 

In the oxidative deamination reaction, the enzyme was active toward N-[l-D-(carboxyl)ethyl]-L-methionine, N-[l-D-(carboxyl)ethyl]-L-phenylalanine, etc. The substrate specificity for amino donors of ODH in the reductive secondary amine-forming reaction was examined with pyruvate as a fixed amino acceptor [15,24]. The enzyme utilized L-norvaline, L-2-aminobutyric acid, L-norleucine, P-chloro-L-alanine, o-acetyl-L-serine, L-methionine, L-isoleucine, L-valine, L-phenylalanine, L-homophenylalanine, L-leucine, L-alanine, etc. 3-Aminobutyric acid and L-phenylalaninol also acted as substrates for the enzyme. Other amino compounds, such as P-amino acids, amino acid esters and amides, amino alcohols, organic amines, hydroxylamines, and hydrazines, were inactive as substrates. Pyruvate, oxaloacetate, glyoxylate, and a-ketobutyrate were good amino acceptors. We named the enzyme as opine... 

There are several examples of d to l inversion of amino acids in the literature. D-Phenylalanine may have therapeutic properties in endogenous depression and is converted to L-phenylalanine in humans [145]. o-Leucine is inverted to the L-enantiomer in rats. When o-enantiomer is administered, about 30% of the enantiomer is converted to the L-enantiomer with a measurable inversion from l to o-enantiomer. As indicated in Fig. 13, D-leucine is inverted to the L-enantiomer by two steps. It is first oxidized to a-ketoisocarproate (KIC) by o-amino acid oxidase. This a-keto acid is then asymmetrically reaminated by transaminase to form L-leucine. In addition, KIC may be decarboxylated by branched-chain a-keto acid dehydrogenase, resulting in an irreversible loss of leucine (Fig. 13) [146]. D-Valine undergoes a similar two-step inversion process, and this can be antagonized by other amino acids such as o-leucine. The primary factor appears to be interference with the deamination process [147]. 

Amino acids are used by the body to form proteins, hormones, and enzymes. Transamination reactions can convert one amino acid into another to meet immediate needs. However, just as there are essential fatty acids, there are also essential amino acids. These amino acids cannot be synthesized in the body and must come from external sources. Humans require phenylalanine, valine, tryptophan, threonine, lysine, leucine, isoleucine, and methionine as essential amino acids. All other amino acids in the body can be synthesized at rates sufficient to meet body needs. If any one of the amino acids necessary to synthesize a particular protein is not available, then the other amino acids that would have gone into the protein are deaminated, and their excess nitrogen is excreted as urea (Ganong, 1963). 

A fermentation study [18] using Streptomyces avermitilis culture 5192 and [1- C] acetate and [1- C] propionate precursors, followed by NMR analysis of the products, established the incorporation of seven acetate and five propionate units into the macrocycle. Carbon 25 and its substituents were shown to be derived from L-isoleucine and l-valine following deamination and conversion into the analogs carboxylic acids. That the C-25 substituent is derived from a... 

A brief discussion of the chemical reactivity of the products of these enzymes is central to our proposed use of these enz)nnes as antinutritive bases of resistance. Polyphenol oxidase (PPO) and peroxidase (POD) oxidize phenolics to quinones, which are strong electrophiles that alkylate nucleophilic functional groups of protein, peptides, and amino acids (e.g., -SH, -NHof -HN-, and -OH)(Figure 1)(53,63-65). This alkylation renders the derivatized amino acids nutritionally inert, often reduces the digestibility of protein by tryptic and chymotryptic enzymes, and furthermore can lead to loss of nutritional value of protein via polymerization and subsequent denaturation and precipitation (63,66-69). POD is also capable of decarboxylating and deaminating free and bound amino acids to aldehydes (e.g., lysine, valine, phenylalanine. 

As shown in Scheme 12.106, deamination (by transamination using 2-oxoglutarate aminotransferase, EC 2.6.1.42, an enzyme requiring pyridoxal) of valine (Val, V) leads to 3-methyl-2-oxobutanoate (e.g., see Scheme 12.17). Introduction of a hydroxymethyl group from 5,10-methylenetretahydrofolate (3-methyl-2-oxobutanoate hydroxymethyltransferase, EC 2.1.2.11) in an aldol-Uke process produces 2-dehydropantoate (4-hydroxy-3,3,-dimethyl-2-oxobutanoate). Stereospecific... 

As with most other amino acids, the catabolism of valine is initiated by removal of its amino group, in this case to yield a-ketoisovaleric acid. L-Valine is readily susceptible to transamination, and it is slowly attacked by L-amino acid oxidase. The n-valine is readily deaminated by D-amino acid oxidase. ... 

The degradation of leucine, isoleucine and valine operates by oxidative deamination and then decarboxylation of the corresponding keto acids. 

When ground and diluted with saline solutions, pig or rat kidney tissue fails to de-aminate 1-amino acids. In the homogenised suspensions, deamination of QL is restored by the addition of oosymase. When supplemented with cozymase and KG, the homogenates deaminate AS, AL, 2-cysteic acid, valine, -leucine and -isoleuoine at rates comparable to their rates of deamination in intact kidney slices deamination in the homogenate is negligible if either eozymase or KG is omitted. 

Studies on banana tissue slices have shown that valine and leucine concentrations increase about threefold following the climacteric rise in respiration [10]. Radioactive labeling studies have shown that valine and leucine are transformed into branched chain flavor compounds that are essential to banana flavor (2-methyl propyl esters and 3-methyl butyl esters, respectively). As can be seen in Figure 4.6, the initial step is deamination of the amino acid followed by decarboxylation. Various reductions and esterifications then lead to a number of volatiles that are significant to fruit flavor (acids, alcohols, and esters). Recent work has shown that amino acids play a role in apple flavor as well. For example, isoleucine is the precursor of 2-methyl butyl and 2-methyl butenyl esters in apples [24,25]. An unusual flavor compound, 2-isobutylthiazole, has been found to be important to the flavor of tomato. It is hypothesized that this compound is formed from the reaction of 3-methyl-l-butanal (from leucine) with cysteamine. 

In summary the D-valinyl moiety of the penicillin molecule is derived from L-valine. The epimerisation during incorporation does not involve deamination. A 2,3-dehydrovalinyl intermediate may be involved but a 3,4-dehydro intermediate is not. The cm-dimethyl groups of valine are incorporated into penicillin with retention of stereochemistry. 

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