Cyclopropane cyclopropanated fatty acid formation

A genus of bacteria, termed the Sphingobacterium, produces sphingolipids by a pathway similar to that in mammals. Clostridia produce plasmalogens (l-alk-l -enyl lipids) by an anaerobic pathway clearly different from the Oj-dependent pathway in mammals (Chapter 9). Branched-chain fatty acids are also found in which the methyl group is inserted post-synthetically into the middle of the chain, in a manner analogous to cyclopropane fatty acid synthesis (Section 5.5). S-adenosylmethionine is also the methyl donor for these reactions. The biochemistry surrounding the formation of these and many other bacterial phospholipids remains to be elucidated. 

Pohl, S., H. J. Law, and R. Ryhage Path of hydrogen in the formation of cyclopropane fatty acids. Biochim. Biophysica Acta (Amsterdam) 70, 583 (1963). 

Other pathways in Fig. 2 lead (1) to the formation of an allylic C-methyl group with transfer of all three hydrogens (structures 1 to 11 to IX as illustrated by smegmamycolic acid. Table IV, or (2) to a cyclopropane ring with the loss of one hydrogen from the methyl group of methionine, (structures I to II to VII) a process exemplified by the formation of the cyclopropane fatty acids of E. coli (Zalkin et al., 1963 Pohl et al., 1963). 

Initial stupes on the in vitro formation of cyclopropane fatty acids revealed that crude extracts of Serratia marcescens and C. butyricum catalyze the formation of cyclopropane fatly acids from S-adenosyl-methionine (Zalkin et al., 1963). Although no lipid or fatty acid requirement could be demonstrated for the reaction catalyzed by S. marcescens extracts, an absolute requirement for a phospholipid that contained an unsaturated fatty add was demonstrated with an extract of C. butyricum. Fvuihermore, the cyclopropane fatty acid formed in the reaction was shown to be one of the fatty acyl chains of phospha-tidylethanolamine. This surprising finding suggested that addition of the methylene bridge to the unsaturated fatty add occurred while the fatty acid was a component of the phospholipid molecule. The over-all reaction is shown in Fig. 11. 

When Law and his colleagues purified cyclopropane synthetase from Clostridium butyricum, they found that the enzyme would catalyse the formation of cyclopropane fatty acids from " C-labelled methionine only if phospholipids were added in the form of micellar solutions. They discovered that the real acceptor for the methylene group was not the fi-ee monounsaturated fatty acid or its CoA or ACP thiol ester, but phosphatidyl ethanolamine - the major lipid of the organism (see Figure 3.16). 

Figure 3.16 Formation of a cyclopropane fatty acid in Clostridium butyricum.

The formation of by-products is also brought about by the presence of a cyclopropane ring in the molecule of the substrate, e.g., some bacterial fatty acids [7]. The aggressive methanol-BF3 reagent must then be replaced with a milder reagent, e.g., 10% (w/v)... 

C=0, -COOH, cyclopropane rings, methyl branches, and C=C bonds. Each species of Mycobacterium contains about two dozen different mycolic acids ° as well as other complex Csq-C fatty acids (see Eq. 21-5). Certain polyunsaturated fatty acids are essential in the human diet (see Box 21-B). One of these, arachidonic acid (which may be formed from dietary linoleic acid), serves as a precursor for the formation of the hormones known as prostaglandins and a series of related prostanoids. Lipids of animal origin also... 

The progressive elongation of this acid leads to the formation of c -vaccenic acid (Cig), a precursor of lactobacillic acid (C19). In this last step, the double bond of the unsaturated acid (the precursor) is methylated to form the corresponding cyclopropanic acid. The fatty acid composition of the bacteria lipids varies during the physiological cycle and is also strongly influenced by several environmental factors. 

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