Relationship Between Pantothenic Acid Requirement and Age in the Rat

Unna, Klaus; Richards, Grace

doi:10.1093/jn/23.6.545

Cited by 28 publications

(2 citation statements)

References 15 publications

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“…The highest levels of pantothenic acid were found in suckling pups, suggesting efficient placental and milk transfer of this vitamin. This difference is consistent with the reported increased need for pantothenic acid in developing young (Unna and Richards 1942). …”

Section: Discussionsupporting

confidence: 91%

Water-soluble vitamin homeostasis in fasting northern elephant seals (Mirounga angustirostris) measured by metabolomics analysis and standard methods

Boaz

Champagne

Fowler

et al. 2012

Comparative Biochemistry and Physiology Part A: Molecular &

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Despite the importance of water-soluble vitamins to metabolism, there is limited knowledge of their serum availability in fasting wildlife. We evaluated changes in water-soluble vitamins in northern elephant seals, a species with an exceptional ability to withstand nutrient deprivation. We used a metabolomics approach to measure vitamins and associated metabolites under extended natural fasts for up to seven weeks in free-ranging lactating or developing seals. Water-soluble vitamins were not detected with this metabolomics platform, but could be measured with standard assays. Concentrations of measured vitamins varied independently, but all were maintained at detectable levels over extended fasts, suggesting that defense of vitamin levels is a component of fasting adaptation in the seals. Metabolomics was not ideal for generating complete vitamin profiles in this species, but gave novel insights into vitamin metabolism by detecting key related metabolites. For example, niacin level reductions in lactating females were associated with significant reductions in precursors suggesting downregulation of the niacin synthetic pathway. The ability to detect individual vitamins using metabolomics may be impacted by the large number of novel compounds detected. Modifications to the analysis platforms and compound detection algorithms used in this study may be required for improving water-soluble vitamin detection in this and other novel wildlife systems.

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Section: Discussionsupporting

confidence: 91%

Water-soluble vitamin homeostasis in fasting northern elephant seals (Mirounga angustirostris) measured by metabolomics analysis and standard methods

Boaz

Champagne

Fowler

et al. 2012

Comparative Biochemistry and Physiology Part A: Molecular &

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“…It is of interest that in rats (38) and guinea pigs (39) the greatest need of the liver for pantothenic acid and CoA is early in development, with a decreasing requirement with progressive age. If a similar developmental pattern of pantothenate and CoA requirement occurs in man, the data may relate to the peculiar susceptibility of very young children to valproate hepatotoxicity (2).…”

Section: Discussionmentioning

confidence: 99%

Amelioration of Adverse Effects of Valproic Acid on Ketogenesis and Liver Coenzyme A Metabolism by Cotreatment with Pantothenate and Carnitine in Developing Mice: Possible Clinical Significance

Thurston

Hauhart

1992

Pediatr Res

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ABSTRACT. Very young children with organic brain damage, intractable seizures, and developmental retardation are at particular risk of developing fatal hepatic dysfunction coincident with valproate therapy, especially if the children are also receiving other anticonvulsant drugs. The mechanism of valproate-associated hepatic failure in these children is unclear. There are two major theories of etiology. The first concerns the manyfold consequences of depletion of CoA due to sequestration into poorly metabolized valproyl CoA and valproyl CoA metabolites. The other theory proposes that the unsaturated valproate derivative 2-n-propyl-4-pentenoic acid and/or metabolically activated intermediates are toxic and directly cause irreversible inhibition of enzymes of B-oxidation. The present study shows for the first time that in developing mice, when pantothenic acid and carnitine are administered with valproate, at least some of the effects of valproate are mitigated. Perhaps most importantly, the /3-hydroxybutyrate concentration in plasma and the free CoA and acetyl CoA levels in liver do not fall so low. Cotreatment with carnitine alone was without effect. Findings support the CoA depletion mechanism of valproate inhibition of Boxidation and other CoA-and acetyl CoA-requiring enzymic reactions and stress the role of carnitine in the regulation of CoA synthesis at the site of action of pantothenate kinase. (Pediatr Res 31: 419-423, 1992) The new anticonvulsant drug, valproic acid (2-n-propylpentanoic acid, 2-n-propylvaleric acid), is particularly effective in the treatment of the types of seizures peculiar to infants and young children: infantile myoclonic spasms, febrile seizures, and petit ma1 (absence) (reviewed in Ref. 1). Yet this is the age group that is most susceptible to the hepatotoxic effects of the drug, particularly if the children have organic brain damage and are also receiving other anticonvulsant drugs (2). In a study of possible mechanisms of this complication, we found that valproate reduced the physiologic ketonemia of suckling mice (3, 4) and fasting epileptic children (5). In the livers of normal developing mice, valproate produced extraordinary decreases in the levels of free CoA, acetyl CoA, and free carnitine (4). Concomitantly, the concentration of medium-chain acyl CoA esters [including valproyl CoA and its metabolites (6)] increased some 6-to 7-fold (4). As in our normal developing mice, valproate also reduced plasma P-hydroxybutyrate levels and liver CoA and acetyl CoA levels in fasted adult rats (7, 8). In isolated adult rat hepatocytes, valproate inhibited oxidation of fatty acids and pyruvate, fatty acid synthesis, gluconeogenesis, ketogenesis, and ureagenesis (6, 7,9-11). In view of the 100 or so synthetic and catabolic enzyme reactions requiring CoA or acetyl CoA as substrates, cofactors, or activators, the above diverse ill effects of valproate on liver metabolism can largely be explained by sequestration of free CoA into nonmetabolized or poorly metabolized valproyl CoA and valpro...

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The Chemistry and Biochemistry of Pantothenic Acid

Williams

1943

Advances in Enzymology - And Related Areas of Molecular Biology

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Relationship Between Pantothenic Acid Requirement and Age in the Rat

Cited by 28 publications

References 15 publications

Water-soluble vitamin homeostasis in fasting northern elephant seals (Mirounga angustirostris) measured by metabolomics analysis and standard methods

Water-soluble vitamin homeostasis in fasting northern elephant seals (Mirounga angustirostris) measured by metabolomics analysis and standard methods

Amelioration of Adverse Effects of Valproic Acid on Ketogenesis and Liver Coenzyme A Metabolism by Cotreatment with Pantothenate and Carnitine in Developing Mice: Possible Clinical Significance

The Chemistry and Biochemistry of Pantothenic Acid

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