Malonyl unit

FIGURE 25.10 Acetyl units are covalently linked to a serine residue at the active site of the acetyl transferase in eukaryotes. A similar reaction links malonyl units to the malonyl transferase. 

Fatty acids are synthesized by a nrultistep route that starts with acetate. The first step is a reaction between protein-bound acetyl and malonyl units to give a protein-bound 3-ketobutyryl unit. Show the mechanism, and tell what kind of reaction is occurring. 

Elongation begins with the joining of the acetyl unit on the condensing enzyme (CE) to a two-carbon part of the malonyl unit on ACP (Figure 22.24). 

Tracing carbons. Consider a cell extract that actively synthesizes palmitate. Suppose that a fatty acid synthase in this preparation forms one molecule of palmitate in about 5 minutes. A large amount of malonyl CoA labeled with i C in each carbon of its malonyl unit is suddenly added to this system, and fatty acid synthesis is stopped a minute later by altering the pH. The fatty acids in the supernatant are analyzed for radioactivity. Which carbon atom of the palmitate formed by this system is more radioactive—C-1 or C-14 ... 

Two plus three to make four. Propose a reaction mechanism for the condensation of an acetyl unit with a malonyl unit to form an acetoacetyl unit in fatty acid synthesis. 

Fatty acid synthesis is essentially the reverse of this process. The process starts with the individual units to be assembled— in this case with an activated acyl group (most simply, an acetyl unit) and a malonyl unit (see Figure 22.2). The malonyl unit condenses with the acetyl unit to form a four-carbon fragment. To produce the required hydrocarbon chain, the carbonyl group is reduced to a methylene group in three steps a reduction,... 

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... 

Two differences exist between fatty acid and complex polyketide syntheses (Fig. 2). First, in fatty acid synthesis, synthase uses only malonyl moieties as extender units to build an acyl chain. In general, acetate is used as the starter unit in vertebrate fatty acid synthase, but bacterial fatty acid synthase may use a branched-chain carboxylic acid as the starter unit because bacterial fatty acids sometimes contain branched-chain fatty acids. In contrast, polyketide synthesis in bacteria uses malonyl, methylmalonyl, and ethylmalonyl units as extenders. In the polyketide synthase, respective extender units are used at every step of the condensation. The polyketide synthase in fungi uses malonyl units as extenders and methyl groups at a positions are added by C-methylation using 5-adenosyl-L-methionine. 

To begin the next series of reactions, a malonyl unit is transferred from malonyl-CoA to the phosphopantotheine site of ACP. In a manner similar to the initial condensation, the homolog containing two additional carbons (in this case, butyryl-ACP) reacts with the malonyl unit, displaces CO2, and is reduced in the next three steps of the reaction sequence (Fig. 2.5). Energy is required to provide the NADPH reduc-tant and (as ATP) to regenerate the thioester linkage of ace-tyl-CoA, and for formation of malonyl-CoA (Lehninger, 1982). The cycle continues until palmitoyl-ACP is produced. 

A number of flavonoids possess a malonyl unit linked to the sugar moieties. Others with malic, oxalic and succinic acid have been reported (Harbome, 1991). 

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