Comparison of serine palmitoyltransferase in Morris hepatoma 7777 and rat liver.
Serine palmitoyltransferase (EC 2.3.1.50) catalyzes an initial and regulatory reaction of sphingolipid biosynthesis, the formation of a homologue of 3-ketosphinganine from L-serine and a fatty acyl coenzyme A thioester. We have demonstrated that this enzyme exists in microsomes from Morris hepatoma 7777 and, moreover, found that its specific activity was 199 +/- 23 pmol/min/mg of microsomal protein, which was significantly higher than that for microsomes from host (69 +/- 4.2 pmol/min/mg; S.D.) or control (43 +/- 4.1 pmol/min/mg) rat livers when assayed under optimal conditions. The activities varied with tumor weight. For comparison, the activities of microsomes from regenerating liver were also higher; whereas fetal and neonatal rat livers had substantially lower activities. Assays conducted without added pyridoxal 5'-phosphate revealed that the enzyme in microsomes isolated from the tumor was more readily depleted of this cofactor than was that in control microsomes; this phenomenon was most pronounced with the larger tumors. The other properties of the enzyme resembled those for liver. On the basis of these experiments, we propose that the elevated proportions of sphingomyelin and other sphingolipids found in hepatomas and regenerating rat liver are related to increases in long-chain base synthesis by serine palmitoyltransferase. Since the activity is apparently more sensitive to the availability of pyridoxal 5'-phosphate in the hepatoma, this reaction could become limiting under more severe vitamin B6 deficiencies.
D000217:Acyltransferases / Q000378:metabolism*; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D005333:Fetus; D007700:Kinetics; D008099:Liver / Q000201:enzymology* / Q000254:growth & development; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D008115:Liver Regeneration; D051381:Rats; D011915:Rats, Inbred BUF; D051102:Serine C-Palmitoyltransferase
D000217:Acyltransferases; D051102:Serine C-Palmitoyltransferase