Coenzyme A,

Coenzymes effecting transfer of groups. Examples of this class are adenosine triphosphate (ATP), biotin, coenzyme A and pyridoxal phosphate. 

Figure C2.5.5. Native stmcture of acyl-coenzyme A binding protein (first NMR stmcture out of 29 deposited to PDB). The figure was created using RasMol 2.6 [8],...

Figure 10.3-19. Representation of the reaction shown fn Figure 10.3-16, indicating all the atoms and bonds of the chemical structures as well as the reaction center. For the sake of clarity, the coenzyme A has been abbreviated.

Although a variety of oxidizing agents are available for this transformation it occurs so readily that thiols are slowly converted to disulfides by the oxygen m the air Dithiols give cyclic disulfides by intramolecular sulfur-sulfur bond formation An example of a cyclic disulfide is the coenzyme a lipoic acid The last step m the laboratory synthesis of a lipoic acid IS an iron(III) catalyzed oxidation of the dithiol shown... 

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... 

Coenzyme A was isolated and identified by Fritz Lipmann an American bio chemist Lipmann shared the 1953 Nobel Prize in physiol ogy or medicine for this work... 

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... 

Using HSCoA and HS—ACP as abbreviations for coenzyme A and acyl carrier protein respectively write a structural formula for the tetrahedral... 

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

Formation of malonyl coenzyme A is followed by a nucleophilic acyl substitution which transfers the malonyl group to the acyl carrier protein as a thioester... 

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... 

Two acyl coenzyme A molecules (R and R may be the same or they may be different)... 

Hydrolysis of the phosphate ester function of the phosphatidic acid gives a diacylglycerol which then reacts with a third acyl coenzyme A molecule to produce a triacylglycerol... 

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... 

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