Evidence of reduction of fumarate to succinate in perfused rat liver under conditions of reduced O2 tension

Hoberman, Henry D.; Prosky, Leon

doi:10.1016/0304-4165(67)90135-3

Cited by 34 publications

(13 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Analysis of a number of glycolytic intermediates and glutamate and aspartate isolated from liver indicated no remarkable changes. All values fell within the normal range reported previously by Hoberman & Prosky (1967). There are indications that cyclamate-fed animals have increased concentrations of glutamate and decreased concentrations of aspartate, lactate and succinate.…”

Section: I972 Discussionsupporting

confidence: 83%

Effects of cyclamate and food restriction on various metabolites in the rat

Prosky

O'Dell

1972

Br J Nutr

View full text Add to dashboard Cite

I. Rats were given stock chow diets containing several levels of calcium cyclamate to study the effects on growth and on some metabolites in liver and blood.2. Levels up to I % in the diet produced diarrhoea without affecting body-weight. At a level of 3 yo in the diet, body-weight was decreased by 12 yo in 8 weeks.3. KO changes were noted in liver protein, lipid and RNA-P and serum protein and lipid.14C0, excretion during the 1st hour after [14C]glucose administration also remained unchanged.4. Adult rats weighing 500 g were given, at a restricted intake, a diet with variations in its fat and cyclamate contents.5. During 15 weeks, the animals given the fat-supplemented diet plus cyclamate lost twice as much weight as controls without cyclaniate and also excreted 20 yo more l'*COz. When the food intake was further restricted for 15 weeks weight losses in all groups were The same. 6. Serum lipid and free cholesterol concentrations were lowered in the cyclamate group.W02 excretion for this group was 35 % higher than for controls, indicating increased metabolic activity. 7. Concentrations of aspartate, glutamate, lactate, succinate, malate and glycerol-Iphosphate in liver werc within normal limits. There were indications of decreased levels of lactate and succinate in cyclamate-fed rats which could be associated with aerobiosis and increased metabolic activity.Until recently, the consumption of artificial sweeteners had increased sharply, mainly through their introduction into beverages and food products. These compounds, which were originally marketed for use by diabetics, were reaching nearly 75 "/o of the population in the United States (Rubini, 1969) at the time cyclamate was withdrawn from the over-the-counter market. At that time their use was still permitted in special food preparations for diabetics or the obese. For the latter, the nonnutritive sweeteners were generally used in combination with food restriction, adding further complications to the metabolic picture. Although the cyclamates are no longer permitted in foods in the Unitcd States their effects on metabolic pathways are still of interest.Fitzhugh (1969) reported that small amounts of dietary cyclamate stimulated appetite with a concomitant increase in body-weight, which could be attributed to increased efficiency of food conversion. These findings, along with the report of inhibition of induction of tryptophan oxygenase when cyclamate was administered by intubation to healthy rats (Sabri, Sharma & Krishna Murti, 1969), prompted us to investigate further the effect of cyclamate on some of the intermediary pathways of energy production in the rat. EXPERIMENTAL Animals and dietsMale rats of the Holtzman strain (100 g) were separated into eleven groups of eight to sixteen animals each. The rats were given a diet of commercial chow (Ralston Purina Co, St Louis, Missouri) supplemented with 0, 0.1, 0.2, 0.5, I, 2, 3 or 4% of calcium cyclamate (Matheson, Coleman and Bell, East Rutherford, New Jersey). The effects of calcium in the diet were checked ...

show abstract

Section: I972 Discussionsupporting

confidence: 83%

Effects of cyclamate and food restriction on various metabolites in the rat

Prosky

O'Dell

1972

Br J Nutr

View full text Add to dashboard Cite

show abstract

“…At first sight it would appear to be evidence in support of mitochondrial transfer by co-factor through coupling of mitochondrial glutamate and malate dehydro genases. However, in view of the very low counts and the fact that [2-3H] -malate did not label glutamate significantly, the more likely interpreta tion is that this finding is not significant and that hydrogen is not trans ferred via NAD in the mitochondrion, which accords with the view ex pressed by Hoberman and Prosky [1967]. On balance, therefore, there is evidence that in the intact animal hydrogen transfer between intermedi ates of the TCA cycle is not mediated by cofactor.…”

Section: Discussionsupporting

confidence: 74%

“…Shanley and Joubert [1973] found no evidence for NAD-dependent fu marate reductase activity in the intact rat. It, therefore, seems that the proposal by Hoberman and Prosky [1967] that succinate dehydrogenase can reduce fumarate has tentative validity in the intact animal, and clear ly, this is an observation of significance.…”

Section: Discussionmentioning

confidence: 99%

Transfer of Hydrogen via Tricarboxylic Acid Cycle Activity to Liver Aspartate and Glutamate in Normal Rats and to Liver Haem in Normal and in Allylisopropylacetamide-Treated Rats

Sm¹,

Bc²

1973

Enzyme

View full text Add to dashboard Cite

“…The difference in labelling of succinate and fumarate is in agreement with the irreversibility of the succinate dehydrogenase reaction under conditions of physiological oxygen tension. An analogous difference in labelling has been observed during metabolism of [2-3H]lactate in perfused rat liver [39]. The hydrogens in succinate are derived from water and acetyl residues [36], and deuterium is therefore not expected to be incorporated during formation of succinate in the forward reactions of the Krebs cycle.…”

Section: Pathways For Labelling Of Acids From (I-2h]ethanolmentioning

confidence: 71%

Transfer of Deuterium from [1‐²H₂]Ethanol to Krebs Cycle and Related Acids of Rat Liver in vivo

Cronholm

Matern

et al. 1974

European Journal of Biochemistry

View full text Add to dashboard Cite

The utilization in intermediary metabolism of hydrogens derived from C-1 in ethanol was studied with the aid of [l-2H,]ethanol. A gas chromatographic-mass spectrometric method was developed and used to measure the deuterium content in individual positions of lactate, malate, 3-hydroxybutyrate, citrate, succinate and fumarate isolated from freeze-clamped livers of rats metabolizing [l-2H,]ethanol (95 atoms% 'H excess) at a maximal rate.A steady state of 2H-labelling was reached within a few minutes. 3-Hydroxybutyrate contained only 1 -2 atoms % of deuterium which was interpreted to indicate that intramitochondrial NADH was essentially unlabelled due to exchange with protons in the NADH dehydrogenase reaction. A low labelling of lactate, 17 atoms %, indicated that the exchange of hydrogens in cytosolic NADH with unlabelled substrates and water was 4 times higher than the rate of ethanol oxidation. Since intramitochondrial oxidation of NADH is not rate limiting, the presence of labelled NADH in the cytosol may indicate that transfer of hydrogen through the mitochondrial membrane is a rate-limiting step.As expected from the reversible reactions catalyzed by fumarate hydratase and malate dehydrogenase the deuterium excess at C-2 and C-3 of malate and fumarate were about the same, 20 atoms %.Citrate had a deuterium excess of about 9 atoms %, assuming that only one hydrogen was labelled.Succinate contained very little deuterium. The labelling of citrate may thus be due either to incorporation of oxaloacetate labelled at C-3 or to labelling of the same hydrogen in a reaction catalyzed by isocitrate dehydrogenase.The results indicate that both malate and isocitrate are potential sources of labelled NADPH during oxidation of [l-2H,]ethanol, and that these two routes are not completely equilibrated under the experimental conditions. Metabolism of ethanol results in an increased ratio between reduced and oxidized members of several redox couples in the liver [l]. This effect is considered to be due to a changed redox state of NAD in the cytosol, resulting from the increased production of NADH in the alcohol dehydrogenase reaction together with a slow transfer of reducing equivalents over the mitochondrial membrane [2,3] or a slow oxidation of intramitochondrial NADH [3,4]. Similar but smaller effects have been noted in redox couples which are in near-equilibrium with NADP [ 5 ] . Previous studies have shown that deuterium from [1-'H2]-ethanol is used directly both in NADH-dependent

show abstract

Evidence of reduction of fumarate to succinate in perfused rat liver under conditions of reduced O2 tension

Cited by 34 publications

References 14 publications

Effects of cyclamate and food restriction on various metabolites in the rat

Effects of cyclamate and food restriction on various metabolites in the rat

Transfer of Hydrogen via Tricarboxylic Acid Cycle Activity to Liver Aspartate and Glutamate in Normal Rats and to Liver Haem in Normal and in Allylisopropylacetamide-Treated Rats

Transfer of Deuterium from [1‐²H₂]Ethanol to Krebs Cycle and Related Acids of Rat Liver in vivo

Contact Info

Product

Resources

About

Evidence of reduction of fumarate to succinate in perfused rat liver under conditions of reduced O2 tension

Cited by 34 publications

References 14 publications

Effects of cyclamate and food restriction on various metabolites in the rat

Effects of cyclamate and food restriction on various metabolites in the rat

Transfer of Hydrogen via Tricarboxylic Acid Cycle Activity to Liver Aspartate and Glutamate in Normal Rats and to Liver Haem in Normal and in Allylisopropylacetamide-Treated Rats

Transfer of Deuterium from [1‐2H2]Ethanol to Krebs Cycle and Related Acids of Rat Liver in vivo

Contact Info

Product

Resources

About

Transfer of Deuterium from [1‐²H₂]Ethanol to Krebs Cycle and Related Acids of Rat Liver in vivo