Methylmalonic acid metabolism and nervous-system fatty acids in cobalamin-deficient fruit bats receiving supplements of methionine, valine and isoleucine.
Cobalamin neuropathy was produced in Cape fruit bats (Rousettus aegyptiacus) by a cobalamin-free diet combined with intermittent exposure to nitrous oxide, which inactivates cobalamin. Cobalamin-deficient bats had low hepatic methylmalonyl-CoA mutase holoenzyme activity, with elevated plasma and urinary methylmalonic acid levels. No significant changes could be demonstrated in the concentration of odd- or branched-chain fatty acids in the nervous system. Supplementation of the cobalamin-free diet with methionine, valine or isoleucine delayed the onset of neuropathy, despite persistence of methylmalonic acid accumulation. Supplementation with any of the three amino acids was associated with elevation of hepatic methionine concentration. The action of valine and isoleucine in delaying the onset of neuropathy can be explained by their methionine-sparing effect. These results emphasize the central role of methionine in the cobalamin neuropathy and do not support the hypothesis that the neuropathy is related to an effect of cobalamin deficiency on the propionic acid pathway.
Department of Haematology, School of Pathology, South African Institute for Medical Research, Johannesburg.
E
E
Vieira-Makings
N
N
Chetty
S C
SC
Reavis
J
J
Metz
D000596:Amino Acids / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002685:Chiroptera / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D007532:Isoleucine / Q000008:administration & dosage / Q000494:pharmacology; D008099:Liver / Q000201:enzymology; D008715:Methionine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D008764:Methylmalonic Acid / Q000378:metabolism*; D008765:Methylmalonyl-CoA Mutase / Q000378:metabolism; D009420:Nervous System / Q000378:metabolism*; D009422:Nervous System Diseases / Q000209:etiology / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism; D014633:Valine / Q000008:administration & dosage / Q000494:pharmacology; D014806:Vitamin B 12 Deficiency / Q000150:complications / Q000378:metabolism*
D000596:Amino Acids; D005227:Fatty Acids; D007532:Isoleucine; D008764:Methylmalonic Acid; D008715:Methionine; D008765:Methylmalonyl-CoA Mutase; D014633:Valine