Acyl-CoA: glycine N-acyltransferase: in vitro studies on the glycine conjugation of straight- and branched-chained acyl-CoA esters in human liver.
Apparent kinetic constants (Km and Vmax values) were determined for human liver acyl-CoA: glycine acyltransferase (glycine-N-acylase) towards isobutyryl-CoA, 2-methyl butyryl-CoA, isovaleryl-CoA, butyryl-CoA, hexanoyl-CoA, octanoyl-CoA, and decanoyl-CoA. These acyl-CoA esters were selected because of their relevance to the human diseases with cellular accumulation of these esters, i.e., especially to metabolic defects in the acyl-CoA dehydrogenation steps of the branched-chain amino acids, lysine, 5-hydroxy lysine, tryptophan, and fatty acid oxidation pathways. With the acyl-CoA ester as the fixed substrate, the Km value for glycine ranged from 0.5 to 2.9 mole/liter, and with glycine as fixed substrate, the Km values for the acyl-CoA esters varied from 0.3 to 5.6 mmole/liter. It is concluded that the substrate concentration is decisive for the glycine conjugate formation and that the occurrence in urine of acylglycines reflects an intramitochondrial accumulation of the corresponding acyl-CoA ester.
Gregersen
N
N
Kølvraa
S
S
Mortensen
P B
PB
D000214:Acyl Coenzyme A / Q000378:metabolism; D000217:Acyltransferases / Q000032:analysis* / Q000302:isolation & purification; D000581:Amidohydrolases / Q000032:analysis / Q000302:isolation & purification; D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology; D044943:Fatty Acid Desaturases / Q000032:analysis / Q000172:deficiency; D005227:Fatty Acids / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008052:Lipid Metabolism, Inborn Errors / Q000201:enzymology; D008099:Liver / Q000201:enzymology*; D013379:Substrate Specificity
D000214:Acyl Coenzyme A; D005227:Fatty Acids; D044943:Fatty Acid Desaturases; D000217:Acyltransferases; C020680:glycine acyltransferase; D000581:Amidohydrolases; C027530:glycine-N-acylase; D005998:Glycine