Co-enzyme A

Figure 4.35 Reduced synthesis tree for Khorana-Todd synthesis of co-enzyme A. Step counts are shown in parentheses.

ABA-l-GAT Arsanilic acid conjugated with the synthetic polypeptide l-GAT AC Adenylate cyclase ACAT Acyl-co-enzyme-A acyltransferase... 

Biocatalytk decarboxylation is a imique reaction, in the sense that it can be considered to be a protonation reaction to a carbanion equivalent intermediate in aqueous medimn. Thus, if optically active compoimds can be prepared via this type of reaction, it would be a very characteristic biotransformation, as compared to ordinary organic reactions. An enzyme isolated from a specific strain of Alcaligenes bronchisepticus catalyzes the asymmetric decarboxylation of a-aryl-a-methyhnalonic acid to give optically active a-arylpropionic acids. The effect of additives revealed that this enzyme requires no biotin, no co-enzyme A, and no ATP, as ordinary decarboxylases and transcarboxylases do. Studies on inhibitors of this enzyme and spectroscopic analysis made it clear that the Cys residue plays an essential role in the present reaction. The imique reaction mechanism based on these results and kinetic data in its support are presented. 

Department biochemistry of vitamins and co-enzymes, A.V. Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, 9 Leontovich str., 01601, Kyiv, Ukraine. 

This enzyme [EC 1.2.7.1], also known as pyruvate ferre-doxin 2-oxidoreductase, catalyzes the reaction of pyruvate with CO enzyme A and oxidized ferredoxin to produce acetyl-CoA, carbon dioxide, and reduced ferredoxin. 

Pantothenic acid (6.25) is a dimethyl derivative of butyric acid linked to / -alanine. Pantothenate is part of the structure of co-enzyme A (CoA), and... 

Sinzinger H, Schmid P, O Grady J. Two different types of exercise-induced muscle pain without myopathy and CK-elevation during HMG-Co-enzyme-A-reductase inhibitor treatment. Atherosclerosis 1999 143(2) 459-60. 

Vitamin B12 is required in humans for several transformations, such as the dependent conversion of (/ )-methylmalonyl co-enzyme A (CoA) into CoA ... 

A decarboxylating, complex dehydrogenase Converts it to acetyl co-enzyme A. 

Quandt L and Huth W (1985) On the mechanism of the chemical modification of the mitochondrial acetyl-CoA acetyltransferase by co enzyme A. Biochimica etBiophysica Acta 829, 103-8. 

Figure 12.1. Pantothenic acid and reiated compounds and co enzyme A Relative molec-uiar masses (Mr) pantothenic acid, 219.2 (caicium dipantothenate,476.5) pantothenol, 214.2 tt)-methyl pantothenic acid, 213.6 homopantothenic acid, 233.2 and eoenzyme A, 767.6. CoASH, free coenzyme A GABA, y-aminobutyric acid.

Figure 14.3. Biosynthesis of choline, and acetylcholine. Relative molecular masses (Mr) choline, 104.2 (chloride, 139.6) and acetylcholine, 146.3 (chloride, 181.7). CoASH, free CO enzyme A...

Li, L., Cheng, X., Lu, S., Nakatsubo, T, Umezawa, T. and Chiang, V.L. (2005) Clarification of cinnamoyl co-enzyme A reductase catalysis in monolignol biosynthesis of aspen. Plant Cell Physiol, 46, 1073-82. 

This soluble, cytosolic enzyme catalyses the 15 -0-acetylation of cardenolide tri- and tetrasaccharides. Using acetyl co-enzyme A as the acetyl donor, acetyl co-enzyme A digitoxin 15 -0-acetyltransferase (DAT) activity was detected... 

In plant systems, de novo synthesis occurs in the plastid and results mainly in the conversion of acetate to palmitate. All 16 carbon atoms in palmitic acid are derived from acetate— half from the methyl carbon and half from the acyl carbon. Two of the carbon atoms (C-15 and C-16) come directly from acetate, and the other 14 come from acetate via the more reactive malonate. Production of malonate requires the incorporation of an additional carbon atom into the acetyl group. This is supplied as bicarbonate, and this same carbon atom is subsequently lost as carbon dioxide. The acyl groups are attached to co-enzyme A (CoASH) during part of the cycle and to acyl carrier protein (ACPSH) during another part. The abbreviated symbols used for these co-enzymes emphasize the thiol groups (SH) to which the acyl chains are attached. 

ALAS is the initial enzyme of the pathway and catalyzes the formation of ALA from succinyl-CoA and glycine. The enzyme is mitochondrial and requires pyridoxal phosphate as a cofactor, which forms a Schiff base with the amino group of glycine at the enzyme surface. The carbanion of the Schiff base displaces Co enzyme A from succinyl-CoA with the formation of a-amino-P-ketoadipic acid, which is then... 

Other lines of evidence also support the notion that deregulated cholesterol homeostasis may contribute to the AD pathogenesis. AD patients have been reported to develop intracellular A/1 accumulation in the late endo-somes and lysosomes. Similar pathological features, including swollen late endosomes and A/ accumulation, have also been reported in Niemann-Pick type C disease patients [52,53], Npcl deficient mice as well as in mouse models of AD [54,55]. The Npcl gene product is essential for the mobihzation of cellular cholesterol. Excess cholesterol can be transported into endoplasmic reticulum and esterified by acyl co enzyme A cholesterol acyltransferase (ACAT) and stored in lipid droplets. Inhibition of ACAT activity has been reported to reduce A/3 levels in vitro and plaque pathology in animal models of AD [56,57]. 

Acyl carrier protein Acyl transferase Malonyl transferase Co-enzyme A... 

A vitamin B12 coenzyme is needed to convert methyknalonyl coenzyme A to succinyl co-enzyme A. Patients with vitamin B12 deficiency almost always have increased urinary excretion of methylmalonic acid (MMA). MMA is amore specific marker for vitamin B12 deficiency compared to homocysteine. MMA levels are not elevated in folate deficiency, as folate does not participate in MMA metabolism. Levels of both MMA and homocysteine are usually elevated prior to the development of hematologic abnormalities and reductions in serum vitamin B12 levels. MMA levels need to be interpreted cau-... 

The statins have achieved major importance as inhibitors of cholesterol biosynthesis and they are used in humans for the treatment of coronary disease. These compounds block isoprenoid formation by inhibiting the key enzyme, hydroxymethylglutaryl co-enzyme A reductase (HMGCoA reductase). This pathway is described in Chapter 5. The active form of the statins, in which the lactone ring is opened, has a formal resemblance to HMGCoA. This inhibition... 

The condensation of acetyl co-enzyme A with oxaloacetic acid and the decarboxylation steps illustrate two of the general metabolic reactions of citric acid intermediates that play an important role in their utilization to form secondary metabolites. 

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