Carnitine biosynthesis from gamma-butyrobetaine and from exogenous protein-bound 6-N-trimethyl-L-lysine by the perfused guinea pig liver. Effect of ascorbate deficiency on the in situ activity of gamma-butyrobetaine hydroxylase.
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.
D000818:Animals; D001206:Ascorbic Acid Deficiency / Q000378:metabolism*; D001622:Betaine / Q000031:analogs & derivatives* / Q000378:metabolism; D002250:Carbon Radioisotopes; D002331:Carnitine / Q000096:biosynthesis*; D006168:Guinea Pigs; D008099:Liver / Q000201:enzymology*; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D008297:Male; D008745:Methylation; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009961:Orosomucoid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D010477:Perfusion; D014018:Tissue Distribution; D014316:Tritium; D050563:gamma-Butyrobetaine Dioxygenase
C042475:6-N-trimethyllysine-agalacto-orosomucoid; D002250:Carbon Radioisotopes; D009961:Orosomucoid; D014316:Tritium; D001622:Betaine; C003712:trimethyllysine; C002889:gamma-butyrobetaine; D006899:Mixed Function Oxygenases; D050563:gamma-Butyrobetaine Dioxygenase; D008239:Lysine; D002331:Carnitine