Valine dehydrogenase

Similar to the work described by Spohn et al. [34], a trienzyme sensor was developed recently for the determination of branched-chain amino acids (L-valine, L-leucine, and L-isoleucine). Leucine dehydrogenase, NADH oxidase, and peroxidase were coimmobilized covalently on tresylate-hydrophylic vinyl polymer beads and packed into a transparent PILL tube (20 cm X 1.0 id), which was used as flow cell. The sensor was free of interferences from protein and NH4+ and it was stable for 2 weeks. The sensor system was applied to the determination of branched-chain amino acids in plasma with recoveries ranging from 98 to 100% [36],... 

Isobutyryl-coenzyme A (CoA) dehydrogenase deficiency (IBD deficiency) is a rare disorder in which the body is unable to process certain proteins properly. People with this disorder have inadequate levels of an enzyme that helps break down the amino acid valine, a building block of proteins. 

Roe CR, Cederbaum SD, Roe DS, Mardach R, Galindo A, Sweetman L. Isolated isobutyryl-CoA dehydrogenase deficiency an unrecognized defect in human valine metabohsm. Mol Genet Metab. 1998 Dec 65(4) 264-71. PubMed citation... 

Isolated isobutyryl-CoA dehydrogenase deficiency an unrecognized defect in human valine metabolism. 

In a muscle at rest, most of the 2-oxo acids produced from transamination of branched chain amino acids are transported to the liver and become subject to oxidation in reactions catalysed by branched-chain 2-oxo acid dehydrogenase complex. During periods of exercise, however, the skeletal muscle itself is able to utilize the oxo-acids by conversion into either acetyl-CoA (leucine and isoleucine) or succinyl-CoA (valine and isoleucine). 

K. F. Gu and T. M. S. Chang, Conversion of ammonia or urea into L-leucine, L-valine and L-isoleucine using artificial cells containing an immobilized multienzyme system and dextran-NAD+, glucose dehydrogenase for co-factor recycling, A 4/0, 11(1), 24-28 (1988). 

The intermediary metabolism has multienzyme complexes which, in a complex reaction, catalyze the oxidative decarboxylation of 2-oxoacids and the transfer to coenzyme A of the acyl residue produced. NAD" acts as the electron acceptor. In addition, thiamine diphosphate, lipoamide, and FAD are also involved in the reaction. The oxoacid dehydrogenases include a) the pyruvate dehydrogenase complex (PDH, pyruvate acetyl CoA), b) the 2-oxoglutarate dehydrogenase complex of the tricarboxylic acid cycle (ODH, 2-oxoglutarate succinyl CoA), and c) the branched chain dehydrogenase complex, which is involved in the catabolism of valine, leucine, and isoleucine (see p. 414). 

SHIKIMATE DEHYDROGENASE SULFITE REDUCTASE VALINE DEHYDROGENASE ZEATIN aS-TRANS ISOMERASE NADPH DEHYDROGENASE NAD(P)H DEHYDROGENASE (QUINONE) NADPH-dependent enzymes, ACYL-ACYL-CARRIER-RROTEIN -DESA-TURASE... 

STEREOCHEMICAL TERMINOLOGY, lUPAC RECOMMENDATIONS VALINE DEHYDROGENASE Valinomydn-like antibiotics,... 

Val Valine or valyl YADH Yeast alcohol dehydrogenase... 

Figure 6b shows the modeled a helix F interface in human 17P-hydroxysteroid dehydrogenase type 2. Alanine-237 is 3 A from the hydrophobic part of the side chain of methionine-241 on the other subunit. Methionine-241 is 3.2 A from serine-234. Alanine-230 is 3.7 A from phenylalanine-242 and 4.5 A from valine-245. Alanine-238, the other anchoring residue, is 4.1 A from alanine-238 on the other subunit. 

Gibson KM, Lee CF, Bennett MJ, Holmes B, Nyhan WL (1993) Combined malonic, methylmalonic and ethylmalonic acid semialdehyde dehydrogenase deficiencies an inborn error of beta-alanine, L-valine and L-alloisoleucine metabolism J Inherit Metab Dis 16 563-567... 

Maple syrup urine disease (branched-chain ketoaciduria) <0.4 Isoleucine, leucine, and valine degradation Branched-chain a-keto acid dehydrogenase complex Vomiting convulsions mental retardation early death... 

FIGURE 18-28 Catabolic pathways for the three branched-chain amino acids valine, isoleucine, and leucine. The three pathways, which occur in extrahepatic tissues, share the first two enzymes, as shown here. The branched-chain -keto acid dehydrogenase complex... 

T There is a relatively rare genetic disease in which the three branched-chain a-lceto acids (as well as their precursor amino acids, especially leucine) accumulate in the blood and spill over into the urine. This condition, called maple syrup urine disease because of the characteristic odor imparted to the urine by the a-lceto acids, results from a defective branched-chain a-lceto acid dehydrogenase complex. Untreated, the disease results in abnormal development of the brain, mental retardation, and death in early infancy. Treatment entails rigid control of the diet, limiting the intake of valine, isoleucine, and leucine to the minimum required to permit normal growth. ... 

Maple syrup urine disease (MSUD) is a recessive disorder in which there is a partial or complete deficiency in branched-chain o-ketoacid dehydrogenase, an enzyme that decarboxylates leucine, isoleucine, and valine (see Figure 20.10). These amino acids and their corre sponding a-keto acids accumulate in the blood, causing a toxic effect that interferes with brain functions. The disease is characterized by feeding problems, vomiting, dehydration, severe metabolic acidosis, and a characteristic maple syrup odor to the urine. If untreated, the disease leads to mental retardation, physical disabilities, and death. 

The mechanism for synthesis of alcohols and aldehydes from amino acids has been discussed in a review by Morgan (1976). Both S. lactis and its malty variant can reversibly form keto acids from the amino acids valine, leucine, isoleucine, methionine, and phenylalanine. However, unlike S. lactis, S. lactis var. maltigenes can decarboxylate these keto acids to form aldehydes and reduce the aldehydes to their corresponding alcohols through the action of alcohol dehydrogenase in the presence of NADH. 

In a rare autosomal recessive condition (discovered in 1954) the urine and perspiration has a maple syrup odor/ High concentrations of the branched-chain 2-oxoacids formed by transamination of valine, leucine, and isoleucine are present, and the odor arises from decomposition products of these acids. The branched-chain amino acids as well as the related alcohols also accumulate in the blood and are found in the urine. The biochemical defect lies in the enzyme catalyzing oxidative decarboxylation of the oxoacids, as is indicated in Fig. 24-18. Insertions, deletions, and substitutions may be present in any of the subunits (Figs. 15-14,15-15). The disease which may affect one person in 200,000, is usually fatal in early childhood if untreated. Children suffer seizures, mental retardation, and coma. They may survive on a low-protein (gelatin) diet supplemented with essential amino acids, but treatment is difficult and a sudden relapse is apt to prove fatal. Some patients respond to administration of thiamin at 20 times the normal daily requirement. The branched-chain oxoacid dehydrogenase from some of these children shows a reduced affinity for the essential coenzyme thiamin diphosphate.d... 

R. N. Patel, L. J. Szarka, and R. H. Mueller, Synthesis of L-/J-hydroxy-valine from a-keto-)3-hydroxyisovalerate using leudne dehydrogenase from Bacillus species, Bioorg. Chem. 1990, 18, 116-130. 

Reductive amination reactions of keto acids are performed with amino acid dehydrogenases. NAD-dependent leucine dehydrogenase from Bacillus sp. is of interest for the synthesis of (S)-fert.-leucine [15-17]]. This chiral compound has found widespread application in asymmetric synthesis and as a building block of biologically active substances. The enzyme can also be used for the chemoenzy-matic preparation of (S)-hydroxy-valine [18] and unnatural hydrophobic bran-ched-chain (S)-amino acids. NAD-dependent L-phenylalanine dehydrogenase from Rhodococcus sp. [19] has been used for the synthesis of L-homophenyl-alanine ((S)-2-Amino-4-phenylbutanoic acid) [9]. These processes with water-soluble substrates and products demonstrate that the use of coenzymes must not... 

Figure 11 The putative catabolic pathway of L-leucine and its implications for strain improvement. For a promising host strain, the pathway to be blocked is indicated with thick double lines and the pathways to be fortified are indicated with thick arrows. Abbreviations for enzymes participating in the L-leucine catabolism and the acylation of tylosin VDH, valine (branched-chain amino acid) dehydrogenase BCDFI, branched-chain a-keto acid dehydrogenase IVD (AcdH), isovaleryl-CoA dehydrogenase (acyl-CoA dehydrogenase) MCC, 3-methylcrotonyl-CoA carboxylase EH, enoyl-CoA hydratase AcyA, mac-rolide 3-O-acyltransferase AcyBl, macrolide 4"-(9-acyltransferase.

A Vancura, I Vancurova, J Vole, SM Fussey, M Flieger, J Neuzil, J Marsalek, V Behai. Valine dehydrogenase from Streptomycesfradiae. purification and properties. J Gen Microbiol 138 3213-3219, 1988. 

As discussed earlier, the avermectin polyketide backbone is derived from seven acetate and five propionate extender units added to an a branched-chain fatty acid starter, which is either (S( I )-a-mcthylbutyric acid or isobutyric acid. The C25 position of naturally occurring avermectins has two possible substituents a. sec-butyl residue derived from the incorporation of S(+)-a-methy lbutyry 1-CoA ( a avermectins), or an isopropyl residue derived from the incorporation of isobutyiyl-CoA ( b avermectins). These a branched-chain fatty acids, which act as starter units in the biosynthesis of the polyketide ring, are derived from the a branched-chain amino acids isoleucine and valine through a branched-chain amino acid transaminase reaction followed by a branched-chain a-keto acid dehydrogenase (BCDH) reaction (Fig. 5) [23]. 

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