W. Dunn, G. Rettura, E. Seifter
Sep 10, 1984
Citations
0
Influential Citations
66
Citations
Quality indicators
Journal
The Journal of biological chemistry
Abstract
The production of carnitine from peptide-bound 6-N-trimethyl-L-lysine (Lys(Me3)) or 4-N-trimethyl-aminobutyrate(gamma-butyrobetaine) perfused through isolated guinea pig livers was investigated. [Methyl-3H] Lys(Me3)-labeled agalacto-orosomucoid (AGOR) and asialofetuin were rapidly taken up and degraded by the perfused liver. Most of the free Lys(Me3) derived from Lys(Me3)-AGOR was released unmodified into the perfusion medium. However, Lys(Me3), arising from Lys(Me3)-asialofetuin was converted mostly to gamma-butyrobetaine and carnitine. gamma-Butyrobetaine added to the perfusion medium was hydroxylated to carnitine by the liver at a rate of 2.3 mumol/h. Guinea pigs maintained on an ascorbate-free diet for 17-60 days showed lowered ascorbate contents in all tissues measured and, coincidentally, a sharp reduction in carnitine levels in kidney, liver, and cardiac, and skeletal muscle. Carnitine production from [1,2,3,4-14C]gamma-butyrobetaine and [methyl-3H]Lys(Me3)-asialofetuin was reduced in perfused livers obtained from ascorbate-deficient guinea pigs. Although hydroxylation of gamma-butyrobetaine to carnitine was effectively depressed in the perfused isolated livers from ascorbate-deficient animals, hydroxylation of [methyl-3H]Lys(Me3) (derived from asialofetuin) to [methyl-3H]3-hydroxy-6-N-trimethyl-L-lysine was unaffected. Prior administration of ascorbate to the medium perfusing the isolated livers caused carnitine biosynthesis from all precursors examined to return to control values.