Methylmalonyl-CoA mutase (EC5.4.99.2) and methionine synthetase (EC2.1.1.13) in the tissues of cobalt–vitamin B₁₂deficient sheep

Abstract

The changes in the activities of the two vitamin B,,-dependent enzymes methylmalonyl-CoA mutase (EC 5.4.99.2) and methionine synthetase (5-methyltetrahydrofolat~homocysteine methyltransferase, EC 2.1.1.13) are described in two groups of sheep maintained for 20 weeks on either a cobalt-deficient or a Co-sufficient whole-barley diet. At the end of that period, the plasma concentrations of vitamin B,, were depressed and those of methylmalonic acid were raised in the Co-deficient group. During the course of the experiment hepatic holo-mutase activity, measured on biopsy samples, declined in Co-deficient animals with a half-life of 73 d. There was a similar, but slower decline in lymphocyte holo-mutase activity which fell with a half-life of 125 d. At slaughter, there was no difference between Co-sufficient and Co-deficient animals in total mutase activity in liver, kidney, brain and spinal cord. In contrast, the total-synthetase activity of liver and kidney was reduced by 60 and 30% respectively in the Co-deficient animals. There was no change in either group of animals in total-synthetase activity, or in either holomutase or holo-synthetase activity, in brain and spinal cord. In the Co-deficient animals, holo-mutase and holo-synthetase activities in liver, the tissue with the greatest activity of both enzymes, fell to 25 and 39 Yo respectively, of that of Co-sufficient animals. The corresponding reductions for kidney were 12 and 51 YO respectively. These results indicated that activity of both holoenzymes is greatly reduced in Co-deficient sheep.Cobalt deficiency : Vitamin B,,-dependent enzymes : Sheep There are three main approaches which may be used to assess changes in the activities of the two vitamin Bl,-dependent enzymes, methylmalonyl-CoA mutase (EC 5.4.99.2) and methionine synthetase (5-methyltetrahydrofolate-homocysteine methyltransferase,

Genomic structure of murine methylmalonyl-CoA mutase: evidence for genetic and epigenetic mechanisms determining enzyme activity

“…Significantly, virtually all of the enzyme in brain was holoenzyme. In other tissues this fraction ranged from 0.3 to 0.6 which is consistent with previous observations in rodents and sheep [5,6,51]. Because The cloning and characterization of murine MCM was undertaken to develop the mouse as a model for molecular genetic investigations of the role that MCM plays in homoeostasis and disease.…”

“…Variability in the level of MCM enzyme activity has been described previously. In sheep and rats, the highest levels of MCM activity were reported in the kidney and liver followed by brain, intestinal mucosa and skeletal muscle [4][5][6]51]. Our [21,26], and that overexpression of MCM in fibroblasts and hepatoma cells does not increase propionate flux above normal [33].…”

Effect of butaphosphan and cyanocobalamin on postpartum metabolism and milk production in dairy cows

“…Moreover, cyanocobalamin, by acting as an enzymatic co-factor to methylmalonyl-CoA mutase enzyme, can also contribute to reduced circulating NEFA (Kennedy et al, 1990). The cyanocobalamin is a vitamin B involved in the synthesis of methionine, a donator of methyl for choline and carnitine.…”

“…Methylmalonyl-CoA mutase, a mitochondrial enzyme, involved in the conversion of propionate to succinyl-CoA, is an important vitamin B12-dependent gluconeogenic substrate (Kennedy et al, 1990). An inadequate supply of vitamin B12, especially in the early lactation, could possibly lead to decreased function of methylmalonyl-CoA mutase, and hinder energy production from propionate, thus leading to enhanced ketogenesis in the animal.…”

Effects of cobalt and copper supplementation on vitamin B₁₂ status and blood parameters in lambs

“…Vitamin B 12 acts as a co-factor for methylmalonyl-CoA mutase and methionine synthase which are important for gluconeogenesis and methionine synthesis. It has been reported that low level of dietary Co can lead to vitamin B 12 defi ciencies clinically manifested as anaemia, inappetence and poor production and biochemically characterized by decrease in the plasma concentration of vitamin B 12 , elevations in the plasma concentrations of methylmalonic acid (MMA) and methionine in ruminants (Kennedy et al, 1990). Copper (Cu) is required for the activity of enzymes associated with iron (Fe) metabolism, normal red blood cell formation and wool pigmentation.…”