A-decarboxylases

Eederici E, B Vitali, R Gotti, MR Pasca, S Gobbi, AB Peck, P Brigidi (2004) Characterization and heterologous expression of the oxalyl coenzyme A decarboxylase gene from Bifidobacterium lactis. Appl Environ Microbiol 70 5066-5073. 

Serine hydroxymethyl transferase catalyzes the decarboxylation reaction of a-amino-a-methylmalonic acid to give (J )-a-aminopropionic acid with retention of configuration [1]. The reaction of methylmalonyl-CoA catalyzed by malonyl-coenzyme A decarboxylase also proceeds with perfect retention of configuration, but the notation of the absolute configuration is reversed in accordance with the CIP-priority rule [2]. Of course, water is a good proton source and, if it comes in contact with these reactants, the product of decarboxylation should be a one-to-one mixture of the two enantiomers. Thus, the stereoselectivity of the reaction indicates that the reaction environment is highly hydro-phobic, so that no free water molecule attacks the intermediate. Even if some water molecules are present in the active site of the enzyme, they are entirely under the control of the enzyme. If this type of reaction can be realized using synthetic substrates, a new method will be developed for the preparation of optically active carboxylic acids that have a chiral center at the a-position. 

ASPARTYLCLUCOSAMINIDASE ASPARTATE AMINOTRANSFERASE ASPARTATE AMMONIA-LYASE ASPARTATE CARBAMOYLTRANSFERASE ASPARTATE a-DECARBOXYLASE ASPARTATE /3-DECARBOXYLASE ASPARTATE KINASE d-ASPARTATE OXIDASE ASPARTATE RACEMASE... 

Combined with levodopa and a decarboxylase inhibitor more stable levodopa levels can be obtained. Tolcapon has been withdrawn in many countries because of serious liverfunction disturbances, rhab-domyolysis and neuroleptic malignant syndrome. 

Specific decarboxylases for most of the common amino acids have been isolated. In mammals, a decarboxylase involved in the biosynthesis of neuroactive amines is particularly important. This enzyme decarboxylates 3,4-dihydroxyphenylalanine and 5-hydroxytryp-tophan (both products of tetrahydrobiopterin-dependent hydroxylations—Section 1.10.5.1) to give 3,4-dihydroxyphenethylamine and serotonin (equation 10), respectively (70MI11002). 

Histidine (bacterial) S-Adenosylmethionine Aspartate a- decarboxylase (3-Alanine... 

Aspartate a-decarboxylase 753, 755 Aspartate p-decarboxylase 746 Aspartate racemase 741 Aspartic acid (Asp, D) 52, 53s biosynthesis 517 pXa value of 293, 487 Aspartic proteases 621-625 Aspartyl aminopeptidase 621 p-Aspartyl phosphate 539, 540s Assays of enzyme activity 456 Assembly core of virus shell 365 Assembly pathway... 

In animals all isoprenoid compounds are apparently synthesized from mevalonate, which is converted by the consecutive action of two kinases21 23 into mevalonate 5-diphosphate (Fig. 22-1, step b). Mevalonate kinase is found predominantly in peroxisomes, which are also active in other aspects of steroid synthesis in humans.2124 A deficiency of this enzyme is associated with mevalonic aciduria, a serious hereditary disease in which both blood and urine contain very high concentrations of mevalonate.23 Mevalonate diphosphate kinase, which is also a decarboxylase, catalyzes phosphorylation of the 3-OH group of mevalonate (step c, Fig. 22-1) and decarboxylative elimination of phosphate (step d)25 to form isopentenyl diphosphate. 

Diseases and disorders resulting from a deficiency of thiamine include beriben, opisthotonos (in birds), polyneuritis, hyperesthesia, bradycardia, and edema. Rather than a specific disease, beriberi may be described as a clinical state resulting from a thiamine deficiency. In body cells, thiamine pyrophosphate is required for removing carbon dioxide from various substances, including pyruvic acid. Actually, this is accomplished by a decarboxylase of which thiamine pyrophosphate is a part. Where... 

A very short and efficient chemoenzymatic synthesis of (—)-ephedrine can be achieved by a decarboxylase-mediated reaction of benzaldehyde with pyruvate... 

Figure 17 Design of assays to evaluate decarboxylation of methylmalonyl-CoA catalyzed by DEBS 1-TE. It was anticipated that a decarboxylase activity would incorporate deuterium into the starter unit of propionyl lactone and that such labeling would be visible by GC-MS analysis. As decarboxylation has been reported in the presence of primers other than propionyl-CoA, assays I—III included n-hutyryl-CoA as a starter unit. Assay IV was designed to evaluate the possibility that -butyryl-CoA suppresses decarboxylation. GC-MS analysis gave no evidence for labeling of the side chain in any assay. Therefore, decarboxylation is not a significant reaction of KSt under these conditions.

In contrast to mammals, /i-alanine 3 is generated in Escherichia coli [12] mainly by decarboxylation of L-aspartate 4 [13] (Scheme 1.6.3). The tetrameric enzyme, l-aspartate-a-decarboxylase (EC 4.1.1.15), was isolated from E. coli [13], cloned [14], and its crystal structure [15] was determined. In bacteria, pantothenate synthase converts /(-alanine to pantothenate, a constituent of coenzyme A [16],... 

Glide docking into L-aspartate a-decarboxylase 333,761 compounds including Maybridge, ZINC, NCI, and FDA drugs were docked in the crystal structure and then narrowed to 703 hits and further limited to 28 and then eight compounds. No experimental validation was reported Sharma et al. (90)... 

Scheme X. Stereochemical mechanism for PLP-dependent L-amino acid a-decarboxylases.

Carboni E, Tanda G, Di Chiara G (1992) Extracellular striatal concentrations of endogenous 3,4-dihydroxyphenylalanine in the absence of a decarboxylase inhibitor—A dynamic index of dopamine synthesis in vivo. / Neurochem 59 2230-2236. 

Geders TW, Gu L, Mowers JC, Liu H, Gerwick WH, Hakansson K, Sherman DH, Smith JL. Crystal structure of the ECH2 catal)4ic domain of CurF from Lyngbya majuscula Insights inot a decarboxylase involved in polyketide chain -branching. J. Biol. Chem. 2007 282 35954-35963. 

When treated with a KS(aIa)/CLF(ala) mutant, no decarboxylation occurred and the malonyl ACP was recovered unchanged. Thus these experiments appear to indicate that the role of the CLF is, at least in part, to provide the acetyl ACP needed to initiate chain assembly. The significance of this result is that if malonyl CoA is the immediate source of both the chain-initiating unit and the chain starter, experiments with wild-type proteins to produce novel metabolites with alternate starter units would not be feasible. However, by impairing the ability of the minimal PKS to produce its own starter, the uptake of added alternate starter units will be facilitated. This may still be a problem because it has been shown that the KS retains a decarboxylase activity and a KS(cys)/CLF(ala) mutant is still capable of producing polyketides, albeit at a greatly reduced level. However, as shown in Figure 10b, addition of acetyl ACP to this restores the rate of polyketide production. 

The safety of entacapone has been specificaUy addressed in a Finnish study in 326 patients (mean age 62 years, 217 men) taking levodopa plus a decarboxylase inhibitor (1). Two-thirds were randomized to take entacapone 200 mg/day and the remainder to take placebo. The withdrawal rate due to adverse events was 14% with entacapone compared to 11% with placebo. Dyskinesias were greatly increased in the former (29 versus 11%) and entacapone was also associated with increased incidences... 

On the other hand, these results have been disputed in another report, with authors in common with the previous report. They presented four case studies, three men and one woman, aged 49-87 years, who had had Parkinson s disease for 8-17 years the longest duration was in the youngest patient (29). All four were taking levodopa (300-1500 mg/day) plus a decarboxylase inhibitor. All four reported sudden irresistible sleep episodes, even during conversations two also complained of sleepiness distinct from these attacks. Two of the patients also had... 

Lysine is formed in bacteria by decarboxylation of meso-diamino-pimelic acid (Fig. 24-14). Glycine is decarboxylated oxidatively in mitochondria in a sequence requiring lipoic acid and tetrahydrofolate as well as PLP (Fig. 15-20). A methionine decarboxylase has been isolated in pure form from a fem. ° The bacterial dialkylglycine decarboxylase is both a decarboxylase and an aminotransferase which uses pyruvate as its second substrate forming a ketone and L-alanine as products (See Eq. 

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