Cytosolic acetylation of sulfamethazine decreases hepatic release of ketone bodies in vivo in fasting rats.
The effect of sulfamethazine (SMZ) on ketogenesis was studied in this report. SMZ, a sulfonamide metabolized by cytosolic acetylation in liver, was intraperitoneally injected (2 mmol/kg) to ketamine-anesthetized, overnight-fasted rats. Ketogenesis was measured by the Fick principle from the transhepatic (A-V) gradients of acetoacetate (AcAc) and D-beta-hydroxybutyrate (beta-OHB). Prior to SMZ injection, A-V gradient of ketone bodies (KB) (AcAc + beta-OHB) was -1.38 mM, indicating release from the liver. After SMZ injection, the release of KB decreased rapidly, maintaining at a level approximately 50% less than controls throughout the 2-h experimental period. Plasma concentrations of AcAc and beta-OHB also decreased. In contrast, plasma concentrations and trans-hepatic gradients of free fatty acids (FFA) were not significantly affected. Our results thus indicate that SMZ acetylation in liver mobilizes acetyl CoA from mitochondria. Decreased hepatic ketogenesis limits the availability of KB and may thus affect energy metabolism in the extrahepatic tissues. The incomplete inhibition on ketogenesis may indicate compartmentation of acetyl CoA in liver mitochondria.
Huang
M T
MT
Laboratory of Metabolism, Chang Gung College of Medicine and Technology, Tao-yuan, Taiwan.
Chen
M Y
MY
Liu
H Y
HY
Shih
H P
HP
D020155:3-Hydroxybutyric Acid; D000105:Acetyl Coenzyme A / Q000097:blood / Q000378:metabolism; D000107:Acetylation; D000818:Animals; D001646:Bile / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005215:Fasting / Q000097:blood / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D006885:Hydroxybutyrates / Q000378:metabolism; D007657:Ketone Bodies / Q000097:blood / Q000378:metabolism*; D007659:Ketones / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013418:Sulfamethazine / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology*
D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D007657:Ketone Bodies; D007659:Ketones; D013418:Sulfamethazine; D000105:Acetyl Coenzyme A; D020155:3-Hydroxybutyric Acid