Butyryl coenzyme

It is generally considered that there are three systems of fatty acid synthesis. The first, which is highly active, is centred in the cell cytoplasm and results mainly in the production of palmitate from acetyl-coenzyme A or butyryl-coenzyme A. Nearly all other fatty acids are produced by modification of this acid. The second system occurs chiefly in the endoplasmic reticulum and to a minor extent in the mitochondria. It involves elongation of fatty acid chains by two-carbon addition, with malonyl-CoA as donor. The third system, confined to the endoplasmic reticulum, brings about desaturation of preformed fatty acids. 

Duncan SH, Barcenilla A, Stewart CS, Pryde SE, Flint HJ. Acetate utilization and butyryl coenzyme A (CoA) acetate-CoA transferase in butyrate-producing bacteria from the human large intestine. Appl Environ Microbiol. 2002 68 5186-5190. 

Hoskins, D.D. (1966), The electron-transferring flavoprotein as a common intermediate in the mitochondrial oxidation of butyryl coenzyme A and sarcosine. J. Biol Chem., 241,4472. 

Steps 6-8 of Figure 29.5 Reduction and Dehydration The ketone carbonyl group in acetoacetyl ACP is next reduced to the alcohol /S-hydroxybutyry] ACP by yS-keto thioester reductase and NADPH, a reducing coenzyme closely related to NADH. R Stereochemistry results at the newly formed chirality center in the /3-hydroxy thioester product. (Note that the systematic name of a butyryl group is biitanoyl.)... 

Reduction and dehydration. The ketone carbonyl group in acetoacetyl ACP is next reduced to an alcohol by NADPH (nicotinamide adenine dinucleotide phosphate), a reducing coenzyme closely related to NADH. Subsequent dehydration of the resulting /3-hydroxy thiol ester (E2 reaction) in step 7 yields crotonyl ACP, and the carbon-carbon double bond of crotonyl ACP is further reduced by NADPH in step 8 to yield butyryl ACP. 

Fatty acids have predominantly even numbers of carbon atoms because they are effectively formed from acetyl (C2) units, which are derived from glucose in the presence of various enzymes, coenzymes and carrier proteins. An overall scheme for saturated fatty acid biosynthesis is presented in Fig. 2.13, in which it can be seen that the first step is the formation of acetyl coenzyme A (often abbreviated to acetyl-CoA). One molecule ofacetyl-CoA undergoes addition of CO, to form malonyl-CoA, while the acetyl group on another molecule is transferred to an enzyme (fatty acid synthase). The malonyl unit (C3) is added to the enzyme-bound acetyl unit, which produces a butyryl group following loss of C02, dehydration and reduction. Six further steps of combined malonyl addition, decarboxylation, dehydration and reduction occur to yield palmitate (C16). Higher acids are built from palmitate in a similar... 

Fig. 2.13 Biosynthesis of saturated fatty acids in plants and animals. Palmitate is formed by successive additions of malonyl coenzyme A to the enzyme-bound chain, with C02 being lost at each addition.This results in chain elongation by a (CH2)2 unit at each step. Details of the formation of butyryl (C4) from acetyl (C2) are shown, while the subsequent six further additions, terminating in palmitate, proceed similarly.

Hydratases that add water to unsaturated fatty acids coupled to coenzyme A (CoA) or acyl carrier protein (ACP) cannot be used in vitro, and consequently have to be applied in whole-cell biotransformations. Prohibitive as this may seem to production on a commercial scale, Kanegafuchi has developed a process, making use of whole cells of Candida rugosa, to produce (R)-2-hydroxybutanoic acid (31) from butanoic acid (30) (Scheme 11.5-5). The series of reactions catalyzed by these cells include coupling of butanoic acid to CoA, desaturation of butyryl-CoA to 2-butenyl-CoA and water addition catalyzed by enolyl-CoA hydratase (enoylase, unsaturated enoyl-... 

Ethyl acetates of fatty acids, mainly ethyl caproate and caprylate, are produced by yeast during alcoholic fermentation. They are synthesized from forms of the acids activated by the coenzyme A (HS-CoA), acyl-S-CoA. Acetyl-S-CoA, from pyruvic acid, may be involved in a Claisen reaction with malonyl-S-CoA, producing a new acyl-S-CoA with two additional carbon atoms (Figure 2.9). Acetyl-S-CoA thus produces butyryl-S-CoA, then hexanyl-S-CoA, etc. Specific enzymes then catalyze the alcoholysis of acyl-S-CoA into ethyl acetates of fatty acids. At the same time, the coenzyme A is regenerated. 

Boynton, Z.L., Bennett, G.N., and Rudolph, EB. (1996) Cloning, sequencing, and expression of clustered genes encoding -hydroxybutyryl-coenzyme A (CoA) dehydrogenase, crotonase, and butyryl-CoA dehydrogenase from Clostridium acetobutylicum ATCC 824. J. Bacteriol, 178, 3015-3024. 

Besides MMCM and GM, two other coenzyme B -dependent carbon skeleton mutases are known. These are (1) methylene glutarate mutase (MGM) from the anaerobe Eubacterium (Clostridium) barkeri, which catalyzes the equilibration of 2-methylene-glutarate with (R)-3-methylitaconate as part of a degradative path of nicotinic acid [175,199] and (2) isobutyryl-CoA mutase (ICM), which is observed in species of gram-positive bacteria Strep-tomyces and catalyzes the reversible rearrangement of iso-butyryl-CoA and n-butyryl-CoA [177]. The isomerization of iso-butyryl-CoA and n-butyryl-CoA in ICM is relevant in the biosynthesis of polyketide antibiotics [177]. 

FIGURE 9.2 Physiology of ABE fermentation metabolism of Clostridium acetobutylicum with the respective enzymes and products. CoA, coenzyme A Ldh, lactate dehydrogenase Pdc, pyruvate decarboxylase Pfor, pyruvate ferredoxin oxidoreductase Fdred, ferredoxin reduced Thl, thiolase Hbd, p-hydroxybutyryl-CoA dehydrogenase Crt, crotonase Bed, butyryl-CoA dehydrogenase Etf, electron transfer flavoprotein Pta, phosphotransacetylase Ack, acetate kinase Ptb, phosphotransbutyrylase Buk, butyrate kinase Ctf A/B, acetoacetyl-CoA acyl-CoA transferase Adc, acetoacetate decarboxylase AdhE, aldehyde/alcohol dehydrogenase Bdh, butanol dehydrogenase. 

The malonyl-coenzyme A then reacts with acyl-carrier protein (ACP), in the presence of malonyl-CoA-ACP transacylase, to give the malonyl-ACP complex. Acetyl-coenzyme A is then coupled with ACP in the presence of acetyl-CoA-ACP transacylase, and this reacts with the malonyl-ACP, the chain length being increased by two carbon atoms to give the butyryl-ACP complex. The reactions involved are shown in Fig. 9.18. 

The butyryl-ACP complex then reacts with malonyl-ACP complex, resulting in further elongation of the chain by two carbon atoms to give caproyl-ACP. Chain elongation takes place by successive reactions of the fattyacyl-ACP complexes with malonyl-coenzyme A until the palmitoyl-ACP complex is produced, when it ceases. Palmitic acid is liberated by the action of a specific deacylase. The overall reaction can be presented as ... 

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