Metabolism of propionate by sheep liver. Stimulation of the mitochondrial rate by factors from the cell sap

Abstract

1. The rate of metabolism of propionate by aged sheep-liver mitochondria in the presence of oxygen + carbon dioxide (95:5) was 5.0 (+/- s.e.m. 0.8) mumoles/mg. of mitochondrial N/hr. 2. When aged in the presence of the mitochondrial supernatant the rate was increased. Mitochondria from 0.33g. of liver, when combined with the corresponding mitochondrial supernatant from 0.08g. of liver, metabolized propionate at a rate of 11.4 (+/- s.e.m. 1.2) mumoles/mg. of mitochondrial N/hr. This rate is comparable with rates previously obtained with aged nuclear-free homogenates. 3. Two factors in the mitochondrial supernatant were detected, which when combined reproduced the effect of the fresh supernatant and prevented loss of activity on aging. One of these was non-diffusible and was recovered by fractionation of the dialysed mitochondrial supernatant with ammonium sulphate. The second factor was present in an ultrafiltrate of fresh mitochondrial supernatant and in boiled mitochondrial supernatant; it was isolated and identified as l(+)-glutamate. 4. The effect of the non-diffusible factor was due to protection of the mitochondria from the aging process, whereas glutamate served both in this capacity and as a direct stimulant of propionate metabolism at low concentration.

Lipid Metabolism

“…Although the molecular weight of the liver apoenzyme is the same that of the holoenzyme, the former is more sensitive to sulfhydryl reagents and to inactivation (62). The conversion of propionate to succinyl-CoA occurs in the mitochondria of sheep liver (63), and the rate of conversion stimulated by catalytic amounts of glutamic acid, a-ketoglutarate, pyruvate, citrate, or isocitrate (64,65). The mechanism of this effect has not yet been defined.…”