The mechanism of Ca2+‐related control of gluconeogenesis in perfused liver


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A kinetic expression for rat‐liver mitochondrial aspartate formation in situ was developed in order to determine whether hormonally induced decreases in 2‐oxoglutarate levels can regulate hepatic gluconeogenesis from lactate via control of aspartate formation. Previous studies from this laboratory showed that 2‐oxoglutarate can inhibit aspartate production by isolated mitochondria. These present studies were designed to probe the physiological significance of the decrease in 2‐oxoglutarate levels observed when Ca2+‐mobilizing gluconeogenic hormones are administered to isolated perfused rat livers. First, estimates were made of the kinetic constants which determine the rate of aspartate formation in isolated mitochondria. The concentrations of the substrates and products of this process were then measured in perfused livers. From these values, it was possible to estimate aspartate efflux from mitochondria in situ. The calculated rates of aspartate production were increased by decreases in 2‐oxoglutarate levels which occurred when glucagon or phenylephrine was added to the perfused livers. Glucagon also effected an inhibition of pyruvate kinase, evidenced by the fact that the calculated rate of aspartate efflux equalled the rate of gluconeogenesis (the difference between the two is equivalent to the pyruvate‐kinase flux). By contrast, in control livers and with phenylephrine stimulation, aspartate formation was higher than gluconeogenesis suggesting significant pyruvate‐kinase flux in this condition. The calculations also show a correlating increase in flux through pyruvate carboxylase (30% with phenylephrine, 15% with glucagon, compared with ∼ 50% increases in gluconeogenic flux). The mechanism of this increase is discussed.

Original languageEnglish (US)
Pages (from-to)143-150
Number of pages8
JournalEuropean Journal of Biochemistry
Issue number1
StatePublished - Feb 1991

All Science Journal Classification (ASJC) codes

  • Biochemistry


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