Pathways of incorporation of fatty acid into glycerolipids of the murine peripheral nervous system in vivo: Alterations in the dysmyelinating mutant trembler mouse

In vivo, glycerolipid metabolism was studied in sciatic nerves of normal and Trembler mice. The results showed that two kinetically independent pathways were implicated In the labeling of diacylglycerophospholipids from [H-3]palmitate: the Kennedy pathway and a 'direct acylation' pathway. In normal nerves, 45% of the glycerophospholipids were labeled, with a rate constant k(3) = 3.9 x 10(-3) min(-1), from phosphatidic acid and diacylglycerol intermediates, themselves formed with a rate constant of k(1) = 0.24 min(-1) from a free H-3-fatty acid pool, FFA(1), that represents 45% of the total injected label. The remaining 55% of the glycerophospholipids were labeled from a kinetically distinct free H-3-fatty acid pool, FFA(2), with a rate constant of k(4) = 9.8 x 10(-2) min(-1), via a process that does not implicate a detectably labeled metabolic intermediate ('direct acylation'). Glycerophospholipid labeling via the Kennedy pathway in the Trembler mouse sciatic nerves was reduced to 75% of the normal level, while labeling via the 'direct acylation' pathway was increased 1.4-fold. The values of the rate constants for free H-3-fatty acid utilisation (k(1) and k(4)) were both increased about 2.5-fold, while that of glycerophospholipid formation from diacylglycerol (k3) was close to normal. Copyright (C) 1996 Elsevier Science Ltd