Hepatic Mitochondrial and Peroxisomal Oxidative Capacity in Riboflavin Deficiency: Effect of Age, Dietary Fat and Starvation in Rats

doi:10.1093/jn/116.10.1992

The Journal of Nutrition

Volume 116, Issue 10, October 1986, Pages 1992-1999

https://doi.org/10.1093/jn/116.10.1992 Get rights and content

Abstract

The effects of riboflavin deficiency on mitochondrial and peroxisomal substrate oxidation were examined in young (treatment begun at weaning) and adult Sprague-Dawley rats that were fed diets low and high in fat. State 3 respiration rates (ADP-stimulated) were used as an estimate of mitochondrial oxidation rates. The oxidation of palmitoyl-CoA and palmitoylcarnitine, and to a lesser extent, glutamate, pyruvate and succinate, by hepatic mitochondria isolated from the young rats was depressed with riboflavin deficiency. There was no effect of dietary fat level on mitochondrial substrate oxidation. Carnitine palmitoyltransferase-A (CPT-A) V_max was increased with riboflavin deficiency and with increasing dietary fat. Cyanide-insensitive palmitoyl-CoA oxidation was used to estimate peroxisomal palmitate oxidation. Expressed as total hepatic capacity, peroxisomal palmitate oxidation was depressed with riboflavin deficiency. This effect was the result of the reduced feed intake rather than riboflavin deficiency per se. Increasing dietary fat resulted in increased peroxisomal palmitate oxidation. Starvation of young rats did not change mitochondrial oxidation rates, although riboflavin-deficient starved rats exhibited increased rates of palmitoyl-CoA oxidation as well as increased CPT-A V_max. In adult rats, after 5 wk of deficiency, only palmitoyl-CoA and palmitoylcarnitine oxidation rates were depressed. Dietary fat level did not interact with riboflavin deficiency. However, CPT-A V_max was increased with riboflavin deficiency and with increased dietary fat level. Further, depressed hepatic fatty acid oxidation can occur in adult rats as a sequel to the feeding of riboflavin-deficient diets.

Literature Cited (26)

HoppelC.L. et al.
Riboflavin and rat hepatic mitochondrial structure and function
J. Biol. Chem
(1979)
BremerJ.
The effect of fasting on carnitine palmitoyltransferase and its inhibition by malonyl-CoA
Biochim. Biophys. Acta
(1981)
SaggersonE.D. et al.
Effect of fasting, adrenalectomy and streptozotocin diabetes on sensitivity of hepatic carnitine palmitoyltransferase to malonyl-CoA
FEBS Lett
(1981)
CookG.A.
Differences in sensitivity of carnitine palmitoyltransferase to inhibition by malonyl-CoA are due to differences in Ki values
J. Biol. Chem
(1984)
TillotsonJ.A. et al.
An enzymatic measurement of riboflavin status in man
J. Nutr
(1971)
GornallA.G. et al.
Determination of serum proteins by means of the biuret reaction
J. Biol. Chem
(1949)
ChenR.F.
Removal of fatty acids from serum albumin by charcoal treatment
J. Biol. Chem
(1967)
HansonR. et al.
Citrate, pyruvate and lactate contaminants of commercial serum albumin
J. Lipid Res
(1968)
HoppelC.L. et al.
Riboflavin and mouse hepatic cell structure and function: mitochondrial oxidative metabolism in severe deficiency state
J. Nutr
(1975)
BurchH.B. et al.
Oxidative enzymes and phosphorylation hepatic mitochondria from riboflavin deficient rats
J. Biol. Chem
(1960)

HaranoY et al.

Carnitine palmitoyltransferase (1 and 2) and the rate of palmitate oxidation in liver mitochondria from diabetic rats

Arch. Biochem. Biophys

(1972)

BradyP.S. et al.

Hepatic mitochondrial and peroxisomal oxidative capacities in riboflavin deficiency

Biochem. J

(1985)

SakuraiT et al.

Riboflavin deficiency and β- oxidative systems in rat liver

Lipids

(1983)

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Hepatic Mitochondrial and Peroxisomal Oxidative Capacity in Riboflavin Deficiency: Effect of Age, Dietary Fat and Starvation in Rats

Abstract

J. Biol. Chem

Biochim. Biophys. Acta

FEBS Lett

J. Biol. Chem

J. Nutr

J. Biol. Chem

J. Biol. Chem

J. Lipid Res

J. Nutr

J. Biol. Chem

Arch. Biochem. Biophys

Hepatic mitochondrial and peroxisomal oxidative capacities in riboflavin deficiency

Biochem. J

Riboflavin deficiency and β- oxidative systems in rat liver

Lipids