Effects of extracellular pH, CO2, and HCO3- on ketogenesis in perfused rat liver.
Effects of extracellular pH, CO2, and HCO3- on ketone body production from octanoate were studied in perfused livers from fasted rats. pH was adjusted to 7.1-7.5 by varying perfusate [HCO3-] and [CO2], where brackets denote concentration. At constant 25 mM [HCO3-], total production of beta-hydroxybutyrate (beta-OHB) + acetoacetate (AcAc) was constant from pH 7.1 to 7.5. However, the [beta-OHB]/[AcAc] ratio decreased from 1.60 to 1.00 when pH decreased from 7.3 to 7.1; there was no change at pH 7.4. At constant [CO2], decreasing pH from 7.4 to 7.1 did not alter either total ketogenesis or the [beta-OHB]/[AcAc] ratio. This suggests that high [CO2] rather than low pH was responsible for the alteration in the redox ratio. At constant pH of 7.4, variations in [HCO3-] between 15 and 25 mM did not influence total ketogenesis or the [beta-OHB]/[AcAc] ratio. However, increasing [HCO3-] from 25 to 35 mM decreased the [beta-OHB]/[AcAc] ratio from 1.76 to approximately 1, again without affecting total ketogenesis. At constant 1.75 mM [CO2], increasing [HCO3-] from 25 to 35 mM also reduced the [beta-OHB]/[AcAc] ratio from 1.63 to approximately 1, suggesting that the effect of high [HCO3-] on this redox ratio can be ascribed to HCO3- itself. It is concluded that high [CO2] or [HCO3-] decreases the mitochondrial [NADH]/[NAD+] ratio in hepatocytes, resulting in a decreased [beta-OHB]/[AcAc] ratio.
Wu
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GY
McGill Nutrition and Food Science Center, Royal Victoria Hospital, Montreal, Quebec, Canada.
Gunasekara
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A
Brunengraber
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H
Marliss
E B
EB
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D005260:Female; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007657:Ketone Bodies / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism*; D009994:Osmolar Concentration; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D001639:Bicarbonates; D007657:Ketone Bodies; D002245:Carbon Dioxide; D006859:Hydrogen