Conservation of central nervous system glutaryl-coenzyme A dehydrogenase in fruit-eating bats with glutaric aciduria and deficient hepatic glutaryl-coenzyme A dehydrogenase.
The adult fruit-eating bat, Rousettus aegypticus, excretes massive amounts of glutaric acid in the urine (20-70 mumol/mg creatinine) comparable to those of humans affected with the inherited metabolic disorder, glutaric aciduria type I. Glutaric acid was quantified by sequential liquid partition chromatography and gas chromatography. Oral loading with the amino acid precursors of glutaric acid, L-lysine and L-tryptophan, resulted in significant increases in glutaric acid excretion above the base-line values. Glutaryl-CoA dehydrogenase activity was assayed in adult bat tissues and compared with the same tissues in the rat using methods of 14CO2 evolution from 1,5-[14C]glutaryl-CoA. A severe deficiency of glutaryl-CoA dehydrogenase activity was found in the bat liver and kidney, whereas brain and spinal cord levels were similar to those in the rat. Reverse phase high performance liquid chromatography analysis of the metabolites in the assay mixture showed negligible hydrolysis of [14C]glutaryl-CoA to free [14C]glutaric acid and complete conversion of the product [14C]crotonyl-CoA to 3-hydroxy[14C]butyryl-CoA. The adult bat, with its huge glutaric acid excretion and deficient liver glutaryl-CoA dehydrogenase, metabolically mimics patients affected with glutaric aciduria type I. The bat does not, however, display the neurologic manifestations seen in patients. This may be explained by conservation of glutaryl-CoA dehydrogenase activity in the central nervous system of the bat.
McMillan
T A
TA
Department of Pediatrics, University of California, San Diego, La Jolla 92093.
Gibson
K M
KM
Sweetman
L
L
Meyers
G S
GS
Green
R
R
D000818:Animals; D002490:Central Nervous System / Q000201:enzymology*; D002685:Chiroptera / Q000378:metabolism*; D005977:Glutarates / Q000652:urine*; D050770:Glutaryl-CoA Dehydrogenase; D008099:Liver / Q000201:enzymology*; D010088:Oxidoreductases / Q000172:deficiency / Q000235:genetics*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D051381:Rats; D013045:Species Specificity
D005977:Glutarates; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; D050770:Glutaryl-CoA Dehydrogenase; C035736:glutaric acid