PATHWAYS OF INCORPORATION OF FATTY-ACID INTO GLYCEROLIPIDS OF THE MURINE PERIPHERAL NERVOUS-SYSTEM IN-VIVO - ALTERATIONS IN THE DYSMYELINATING MUTANT TREMBLER MOUSE

In vitro, glycerolipid metabolism was studied in sciatic nerves of nor mal and Trembler mice. The results showed that two kinetically indepen dent pathways were implicated In the labeling of diacylglycerophosphol ipids from [H-3]palmitate: the Kennedy pathway and a 'direct acylation ' pathway. In normal nerves, 45% of the glycerophospholipids were labe led, with a rate constant k(3) = 3.9 x 10(-3) min(-1), from phosphatid ic acid and diacylglycerol intermediates, themselves formed with a rat e 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 l abeled metabolic intermediate ('direct acylation'). Glycerophospholipi d labeling via the Kennedy pathway in the Trembler mouse sciatic nerve s was reduced to 75% of the normal level, while labeling via the 'dire ct acylation' pathway was increased 1.4-fold. The values of the rate c onstants 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 Else vier Science Ltd