Synthesis of fatty acids in outer and inner membranes of mitochondria.

Fatty acids can be synthesized in mitochondrial membranes of rat liver either by elongation or by synthesis de nouo. The outer membranes incorporate greater amounts of substrate into fatty acids than do the inner membranes. Outer membranes synthesize 6and g-carbon fatty acids completely de nouo, while smaller amounts of lo-carbon acids are produced by the mechanism de novo. The reactions de novo utilize acetyl coenzyme A more effectively than malonyl coenzyme A, and synthesis de novo occurs in the absence of exogenous ATP. Elongation, which produces fatty acids 14 carbon atoms long and longer, depends on added ATP, and acetyl-CoA and malonyl-CoA are incorporated about equally. Synthesis de novo of shorter chain fatty acids by outer membranes continues in the presence of ATP and the concomitant elongation reactions. Inner membranes synthesize only longer fatty acids by elongation. If synthesis de novo of fatty acids occurs in the inner membranes, these acids might be removed by oxidation. The ATP concentrations in these experiments were compared with the levels of ATP produced by actively respiring liver mitochondria. During metabolically adverse conditions within the cell, the capacity for manufacturing fatty acids by elongation may fluctuate with the ATP levels whereas synthesis de nouo continues.