On the Mechanism of Malonyl‐CoA‐Independent Fatty‐Acid Synthesis

Abstract

1 NADPH-specific mitochondrial enoyl-CoA reductase can be assayed by a sensitive radioactive test, employing tritium-labelled NADPH, synthesized in a prefixed reacton from d-[1-³H]glucose via the hexokinase and glucose-6-phosphate dehydrogenase reactions. 2 Liver, kidney cortex, heart muscle, skeletal muscle, brown adipose tissue, brain cortex, and aortic intimal tissue are investigated concerning chain lengths specificity of the chain elongation and the enoyl-CoA reductase. Medium-chain acyl-CoA compounds prove to be the best primers for the chain, elongation. Enoyl-CoA reductases still show large incorporation rates with hexadecenoyl-CoA. 3 The differences in the chain lengths specificity of the chain elongation and enoyl-CoA reductase can be explained, by the inhibitory effect of long-chain acyl-CoA derivatives on the 3-hydroxyacyl-CoA dehydrogenase. 4 The nucleotide specificity in the different tissues reveals two types of chain elongation: In addition to liver and kidney cortex, mitochondria of brown adipose tissue need NADH + NADPH for optimal chain elongation, whereas heart muscle, skeletal muscle and aortic intimal mitochondria only need NADH. 5 Different physiological roles are proposed for the two types. The “heart type” may he of importance in the conservation of reducing equivalents or acetate units in the anaerobic state the “liver type” may play a role in the transfer of hydrogen from NADPH to the respirator chain. In addition, the mitochondria(chain elongation may serve as bypass of the first part of the respiratory chain