The effects of hypoglycin on glucose metabolism in the rat. A kinetic study in vivo and [U-14C,2-3H]glucose

Abstract

1. The kinetics of glucose metabolism were evaluated in rats deprived of food 15-21 h after the administration of hypoglycaemic doses of hypoglycin (100 mg/kg body wt.) by following changes in the specific radioactivities of 14C and 3H in blood glucose after an intravenous dose of [U-14C,2-3H]glucose [Katz, Rostami & Dunn (1974) Biochem. J. 142, 161-170]. 2. During this time, recycling of glucose through the Cori cycle was virtually abolished, the rate of irreversible disposal of glucose and its total body mass were both decreased by about 70%, whereas there was little effect on the mean transit time for glucose. 3. It was concluded that hypoglycaemia is due to inhibition of gluconeogenesis.

Turnover of fatty acyl‐CoA oxidase in the liver of rats fed on a partially hydrogenated marine oil

“…The effects observed in rats given a partially hydrogenated marine oil (PHMO) in a high-fat diet are very pronounced compared with the responses seen in rats fed peanut or safflower oil diets (13,(14)(15)(16)(17). The reason for the increase in hepatic peroxisomal/3-oxidation in rats given a PHMO-diet is still not clear, although it has been speculated that it may be triggered by an accumulation of CoA esters of long-chain and very long-chain unsaturated fatty acids (12,18) which are poorly oxidized by mitochondria (19). No kinetic studies on the turnover of peroxisomal/3-oxidation enzymes in a high-fat diet condition have been performed.…”

Inhibition of gluconeogenesis in isolated rat liver cells by methylenecyclopropylpyruvate (ketohypoglycin)

“…An alternative explanation, that the inhibitor may block pyruvate uptake into mitochondria, as shown to occur with other pyruvate analogues (Land & Clark, 1974), is less likely, since methylenecyclopropylacetate, which has otherwise similar effects, does not affect pyruvate oxidation in isolated mitochondria (Billington et al, 1978 We are unable to account fully for the varied degrees of inhibition observed with the different substrates. This would require fairly precise information, not presently available, on the response of the rate-limiting step in each separate case.…”

“…We conclude that the effects of methylenecylcopropylpyruvate on gluconeogenesis are largely attributable to changes in acyl-CoA/CoA distribution with its consequent enzymic effects (Billington et al, 1978), although the limitation of the concentration of CoA as a factor cannot be excluded for all substrates.…”

“…The generation of methylenecyclopropylacetyl-CoA from methylenecyclopropylpyruvate specifically inhibits butyryl-CoA dehydrogenase (Kean, 1976c;Billington et al, 1978) in the mitochondrial compartment. This primary action triggers secondary effects.…”

“…One hypothesis is that fatty acid oxidation is blocked by methylenecyclopropylacetyl-CoA, which inhibits short-chain acyl-CoA dehydrogenase (EC 1.3.99.2;Osmundsen & Sherratt, 1975;Kean, 1976c;Osmundsen et al, 1978 (Billington et al, 1978). An alternative hypothesis (Bressler et al, 1969;Corredor, 1976), which has been strongly criticized (Sherratt & Osmundsen, 1976), is that the effects are more directly attributable to sequestration of CoA and carnitine by hypoglycin derivatives, the rates of several metabolic processes being consequently slowed.…”