1 54 CARBON METABOLISM III 



cells. Interest in the problem was first aroused by the finding that 

 methyl ketones are present in certain of the fungal cheeses and in 

 edible oils attacked by fungi (482, 494). In a number of experiments 

 it has been shown that Penicillium glaucum converts a fatty acid to 

 a methyl ketone of one less carbon atom, i.e., 



R _CH 2 — CHo— COOH -* R— CO— CH 3 + C0 2 (6) 



This reaction has been demonstrated in experiments on many fatty 

 acids (2, 509, 511), e.g.: 



CH.3— CHo— CHo— COOH -> CH 3 — CO— CH 3 (7) 



Butyric acid Acetone 



CH 3 — (CH 2 ) 6 — COOH -* CH 3 — (CH 2 ) 4 — CO— CH 3 (8) 



Octanoic acid Methylamyl ketone 



CH 3 — (CH 2 ) 10 — COOH -* CH 3 — (CH 3 ) 8 — CO— CH 3 (9) 



Dodecanoic acid Methylnonyl ketone 



The same general reaction is found in Penicillium notatum and in 

 Aspergillus spp. (149, 380, 569). 



Thaler and co-workers (510) propose the following sequence of 

 reactions in the formation of methyl ketones from fatty acids: 



R-CH 2 - CHo— COOH -» R— CH=CH— COOH 



Fatty acid a, ^-Unsaturated fatty acid 



-> R—CHOH— CHo— COOH 



/3-Hydroxy fatty acid 



-* R— CO— CHo— COOH -> R— CO— CH 3 + C0 2 (10) 



/S-Keto fatty acid Methyl ketone 



The evidence for this sequence is that methyl ketones arise during the 

 growth of Penicillium glaucum on «,/?-unsaturated acids and /?-hy- 

 droxy acids. Thus, methylpropyl ketone is formed from hexanoic 

 acid, 2-hexanoic acid, and /3-hydroxyhexanoic acid. Further, fungi 

 are known to form /3-keto acid decarboxylases (309). 



This scheme, up to the formation of the /3-keto acid, agrees with our 

 current understanding of the process in animal cells, but until en- 

 zymatic studies are made, the identity of the two systems remains 

 hypothetical. The last step — formation of the methyl ketone — does 

 not go on appreciably in the normal animal cell, which instead forms, 

 as mentioned above, a 2-carbon compound and a new fatty acid. This 

 suggests that methyl ketone formation by fungi is an abnormal or at 

 least unusual reaction, perhaps to be attributed to toxicity of the 

 substrate fatty acid (494). It is reasonable to suppose that complete 

 oxidation of fatty acids in the fungi follows the animal system, with 

 liberation of acetyl-coenzyme A or free acetate as the last step. The 



