Coenzyme A , acetyl

The form in which acetate is used in most of its important biochemical reactions is acetyl coenzyme A (Figure 26 la) Acetyl coenzyme A is a thwester (Section 20 13) Its for matron from pyruvate involves several steps and is summarized m the overall equation... 

All the individual steps are catalyzed by enzymes NAD" (Section 15 11) is required as an oxidizing agent and coenzyme A (Figure 26 16) is the acetyl group acceptor Coen zyme A is a thiol its chain terminates m a sulfhydryl (—SH) group Acetylation of the sulfhydryl group of coenzyme A gives acetyl coenzyme A... 

As we saw m Chapter 20 thioesters are more reactive than ordinary esters toward nucleophilic acyl substitution They also contain a greater proportion of enol at equilib rmm Both properties are apparent m the properties of acetyl coenzyme A In some reactions it is the carbonyl group of acetyl coenzyme A that reacts m others it is the a carbon atom... 

Fatty acids are biosynthesized by way of acetyl coenzyme A The following sec tion outlines the mechanism of fatty acid biosynthesis... 

We can descnbe the major elements of fatty acid biosynthesis by considering the for mation of butanoic acid from two molecules of acetyl coenzyme A The machinery responsible for accomplishing this conversion is a complex of enzymes known as fatty acid synthetase Certain portions of this complex referred to as acyl carrier protein (ACP), bear a side chain that is structurally similar to coenzyme A An important early step m fatty acid biosynthesis is the transfer of the acetyl group from a molecule of acetyl coenzyme A to the sulfhydryl group of acyl carrier protein... 

A second molecule of acetyl coenzyme A reacts with carbon dioxide (actually bicarbonate ion at biological pH) to give malonyl coenzyme A... 

The four carbon atoms of the butanoyl group originate m two molecules of acetyl coenzyme A Carbon dioxide assists the reaction but is not incorporated into the prod uct The same carbon dioxide that is used to convert one molecule of acetyl coenzyme A to malonyl coenzyme A is regenerated m the decarboxylation step that accompanies carbon-carbon bond formation... 

The introduction to Section 26 8 pointed out that mevalonic acid is the biosynthetic pre cursor of isopentenyl pyrophosphate The early steps m the biosynthesis of mevalonate from three molecules of acetic acid are analogous to those m fatty acid biosynthesis (Sec tion 26 3) except that they do not involve acyl earner protein Thus the reaction of acetyl coenzyme A with malonyl coenzyme A yields a molecule of acetoacetyl coenzyme A... 

Carbon-carbon bond formation then occurs between the ketone carbonyl of acetoacetyl coenzyme A and the a carbon of a molecule of acetyl coenzyme A... 

Chemists and biochemists And it convenient to divide the principal organic substances present m cells into four mam groups carbohydrates proteins nucleic acids and lipids Structural differences separate carbo hydrates from proteins and both of these are structurally distinct from nucleic acids Lipids on the other hand are characterized by a physical property their solubility m nonpolar solvents rather than by their structure In this chapter we have examined lipid molecules that share a common biosynthetic origin m that all their carbons are derived from acetic acid (acetate) The form m which acetate occurs m many of these processes is a thioester called acetyl coenzyme A... 

Abbreviation for acetyl coenzyme A (for complete stmcture see Figure 26 1)... 

Acetyl coenzyme A is the biosynthetic precursor to the fatty acids, which most often occur naturally as esters Fats and oils are glycerol esters of long chain carboxylic acids Typically these chains are unbranched and contain even numbers of carbon atoms... 

IS the key carbon-carbon bond forming step Acetyl coenzyme A (Section 26 1) A thiol ester abbreviated as... 

Methyl group (Section 2 7) The group —CH3 Mevalonic acid (Section 26 10) An intermediate in the biosyn thesis of steroids from acetyl coenzyme A Micelle (Section 19 5) A sphencal aggregate of species such as carboxylate salts of fatty acids that contain a lipophilic end and a hydrophilic end Micelles containing 50-100 car boxylate salts of fatty acids are soaps Michael addition (Sections 18 13 and 21 9) The conjugate ad dition of a carbanion (usually an enolate) to an a 3 unsatu rated carbonyl compound... 

Iron Sulfur Compounds. Many molecular compounds (18—20) are known in which iron is tetrahedraHy coordinated by a combination of thiolate and sulfide donors. Of the 10 or more stmcturaHy characterized classes of Fe—S compounds, the four shown in Figure 1 are known to occur in proteins. The mononuclear iron site REPLACE occurs in the one-iron bacterial electron-transfer protein mbredoxin. The [2Fe—2S] (10) and [4Fe—4S] (12) cubane stmctures are found in the 2-, 4-, and 8-iron ferredoxins, which are also electron-transfer proteins. The [3Fe—4S] voided cubane stmcture (11) has been found in some ferredoxins and in the inactive form of aconitase, the enzyme which catalyzes the stereospecific hydration—rehydration of citrate to isocitrate in the Krebs cycle. In addition, enzymes are known that contain either other types of iron sulfur clusters or iron sulfur clusters that include other metals. Examples include nitrogenase, which reduces N2 to NH at a MoFe Sg homocitrate cluster carbon monoxide dehydrogenase, which assembles acetyl-coenzyme A (acetyl-CoA) at a FeNiS site and hydrogenases, which catalyze the reversible reduction of protons to hydrogen gas. 

The neurotransmitter must be present in presynaptic nerve terminals and the precursors and enzymes necessary for its synthesis must be present in the neuron. For example, ACh is stored in vesicles specifically in cholinergic nerve terminals. It is synthesized from choline and acetyl-coenzyme A (acetyl-CoA) by the enzyme, choline acetyltransferase. Choline is taken up by a high affinity transporter specific to cholinergic nerve terminals. Choline uptake appears to be the rate-limiting step in ACh synthesis, and is regulated to keep pace with demands for the neurotransmitter. Dopamine [51 -61-6] (2) is synthesized from tyrosine by tyrosine hydroxylase, which converts tyrosine to L-dopa (3,4-dihydroxy-L-phenylalanine) (3), and dopa decarboxylase, which converts L-dopa to dopamine. 

Fig. 1. CAT (catalyzed acetylation) of chloramphenicol (1, R = NO2), and thiamphenicol (1, R = CH2SO2) where Ac-CoA is acetyl coenzyme A [72-89-9].

Acetylcholine is the product of the reaction between choline and acetyl coenzyme A in the presence of choline acetylase (41). 

Fig. 2. Kiebs (citiic acid) cycle. Coenzyme A is lepiesented CoA—SH. The cycle begins with the combination of acetyl coenzyme A and oxaloacetic acid to...

Glyoxylate cycle A modification of the Krebs cycle, which occurs in some bacteria. Acetyl coenzyme A is generated directly from oxidation of fatty acids or other lipid compounds. 

Krebs Cycle The oxidative process in respiration by which pyruvate (via acetyl coenzyme A) is completely decarboxylated to COj. The pathway yields 15 moles of ATP (150,000 calories). 

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