Abstract
Abstract Cycloheximide (3 to 5mm) caused a decrease in the rate of gluconeogenesis from pyruvate, lactate, or glycerol in the perfused rat and guinea pig liver. In these experiments, oxygen consumption was reduced by 30% with pyruvate but was unaltered with lactate or glycerol as substrates. The inhibition of gluconeogenesis caused by cycloheximide was rapid in onset (100% of maximal inhibition in 1 to 2 min) and immediately reversible upon cessation of cycloheximide infusion. Perfused livers were freeze-clamped in situ before and during cycloheximide infusion and the mitochondrial NAD:NADH ratio was calculated by a measurement of intermediates of the β-hydroxybutyrate dehydrogenase couplet. There was a marked shift toward reduction of the intramitochondrial pool of nicotinamide coenzymes after cycloheximide infusion. Under these conditions, the hepatic levels of ATP, ADP, and AMP were not significantly altered by cycloheximide in livers of rats perfused with lactate. With pyruvate as substrate, the ratio of ATP:ADP was decreased although no change in AMP levels was observed. Our findings indicate that the metabolic effects of cycloheximide are rapidly reversed, with the inhibitory effect on gluconeogenesis not evident after 10 min of recycling of the perfusate through the liver. Previous studies with cycloheximide have shown this compound to block mitochondrial energy transfer at Site I of the respiratory chain. It is suggested that cycloheximide decreases the rate of hepatic gluconeogenesis by an inhibition of mitochondrial energy transfer at Site I.
Highlights
Immediately reversible upon cessation of cycloheximide infusion
Gluconeogenesis from pyruvate (2 mw) b> isolated rat liver was progressively inhibited with increasing concentrations of cycloheximide, such that a concentration of 10 rnhf cycloheximide caused a 92% inhibition in glucose formation (Fig. I)
When the infusion of cycloheximide was stopped, the the rate of glucose formation returned to levels approximately 6Oc/, of those noted before the infusion
Summary
Cycloheximide (3 to 5 mM) caused a decrease in the rate of gluconeogenesis from pyruvate, lactate, or glycerol in the perfused rat and guinea pig liver. In these experiments, oxygen consumption was reduced by 30% with pyruvate but was unaltered with lactate or glycerol as substrates. In preliminary experiments with this system both rat and guinea pig livers TJ-ere perfused for 120 min with Krebs-Ringer bicarbonate buffer, containing 2 mM lactate and 0.4 mM octanoate, with or without 37, defatted bovine serum albumin. The concentration of acetoacetate and P-hydroxybutyrate (lo), ATl’ (II), ADl-’ and AMP [12] were determined enzymatically
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
