Colleen M. Smith

Comparative nutrition of pantothenic acid

Abstract Pantothenic acid, a B-vitamin, is essential for all mammalian species that have been studied: humans, calves, pigs, dogs, rodents, and cats, as well as for poultry and fish. The different species develop various deficiency signs such as growth retardation; anorexia; changes in hair, feather, or skin; locomotor abnormalities; gastrointestinal problems; compromised immunofunctions; impaired adrenal functions; altered lipid and carbohydrate metabolism; and adverse breeding outcome. Because there are no reliable and sensitive criteria for assessing pantothenate status, the dietary requirements of different species are most frequently set at the level that results in maximum growth. The pantothenate requirement varies widely among different species and strains, and depends on the age, growth rate, and breeding stages of the animals. This review summarizes the deficiency signs and the requirements for pantothenate of different species, and discusses various factors that affect pantothenate requirements of the animals.

Inhibition of d(-)-3-hydroxybutyrate dehydrogenase by malonate analoges

Abstract (1) d (-)-3-Hydroxybutyrate dehydrogenase activity from guinea pig, rat, and bovine heart and from guinea pig liver is inhibited by malonate and tartronate, and more potently by the analogs methylmalonate, bromomalonate, chloromalonate, and mesoxalate. Little or no inhibitory effect was found for aminomalonate, ethylmalonate, dimethylmalonate, succinate, glutarate, oxaloacetate, malate, propionate, pyruvate, d - and l -lactate, n -butyrate, isobutyrate, and cyclopropanecarboxylate. (2) In initial velocity kinetics at pH 8.1 with a soluble enzyme preparation from bovine heart, the inhibition by the active malonate derivatives is competitive with respect to 3-hydroxybutyrate and uncompetitive with respect to acetoacetate, NAD + or NADH. With d -3-hydroxybutyrate as the variable reactant ( K m app = 0.26 mM) the inhibition constant of methylmalonate ( K is ) was 0.09 m m . (3) The rate of utilization of d -3-hydroxybutyrate (78 μ m ) by coupled rat heart mitochondria in the presence of ADP was inhibited 50% by 150 μ m methylmalonate. (4) With coupled guinea pig liver mitochondria oxidizing n -octanoate in the absence of added ADP, methylmalonate (1–3 m m ) depressed 3-hydroxybutyrate formation substantially more than total ketone production. However, the intramitochondrial NADH (or NADPH) levels were unchanged by the addition of methylmalonate, indicating that the changes in ratios of accumulated 3-hydroxybutyrate and acetoacetate were caused by direct inhibition of 3-hydroxybutyrate dehydrogenase. Methylmalonate had the same effect on 3-hydroxybutyrate/acetoacetate ratios and ketone body formation with pyruvate or acetate as the source of acetyl groups. Similar results were obtained with malonate (10 m m ) although the inhibition of total ketone formation from octanoate was more severe.

The effect of pantothenate deficiency in mice on their metabolic response to fast and exercise

The changes in fuel metabolism during fast and exercise were compared to the tissue total CoA levels in mice maintained on pantothenate-deficient and pantothenate-supplemented (control) diets. In nonexercised mice maintained on a pantothenate-deficient diet for 65 to 105 days, the total CoA levels of many tissues were significantly lower than in controls (liver 18%, kidney 23%, spleen 21%, heart 38%, and leg skeletal muscle 66%). However, no differences in total CoA levels in brain or epididymal fat pads were observed. During a 48-hour fast, the total CoA levels increased in the heart and liver of both pantothenate-deficient and control mice (heart 32 and 19%, respectively; liver 39 and 45%, respectively), but the level of total CoA remained lower in the deficient mice. Liver glycogen levels were 17% lower in deficient mice than in controls and liver ketone bodies were 17% higher in pantothenate deficient mice than in controls. Separate groups of mice on deficient and supplemented diets were trained to run to exhaustion. Compared to trained mice on pantothenate-supplemented diets, the trained pantothenate-deficient mice had lower running times until exhaustion, lower body weights, lower liver and muscle glycogen content (even after rest), and elevated liver ketone bodies both during rest and after running. In summary, the pantothenate-deficient mice were unable to maintain normal glycogen stores, but had a normal ketogenic response to fast and exercise in spite of the lower levels of liver total CoA.

The effect of ethanol and acetaldehyde on [14C]pantothenate incorporation into CoA in cultured rat liver parenchymal cells

Abstract The effect of ethanol on [ 14 C]pantothenate incorporation into CoA and on total CoA levels was measured in 3-day-old primary cultures of adult rat liver parenchymal cells. Ethanol decreased the incorporation of radioactivity into CoA a maximum of 67%, 5 m m ethanol was saturating for the inhibitory effect and 0.2 m m ethanol was sufficient for half-saturation. This inhibitory effect did not result from a loss of CoA precursors or from cell death. Ethanol concentrations up to 10 m m did not decrease the ATP content of cells or the total protein content of cells which adhered to the incubation flask. Ethanol (5 m m ) had no effect on the cyteine + cystine content of the cells. Intracellular pantothenate concentrations were not affected by 5 m m ethanol, and increasing the pantothenate concentration did not affect ethanol inhibition. Ethanol inhibition of [ 14 C]pantothenate conversion to CoA could be fully reversed by rinsing the cells free of ethanol. The ethanol inhibition could also be fully reversed by addition of 4-methylpyrazole, indicating that ethanol must be oxidized via alcohol dehydrogenase to exert its inhibitory effect. Acetaldehyde, the immediate product of alcohol dehydrogenase, was also an inhibitor of the incorporation of [ 14 C]pantothenate into CoA; the maximum inhibition was 63%. Acetaldehyde concentrations maintained between 18 and 103 μ m inhibited incorporation by 57%. The inhibition by acetaldehyde did not correlate well with changes in the NADH and NAD + ratio of the cells (as determined by measuring changes in the lactate-to-pyruvate ratio). The ability of glucagon, dibutyryl cAMP + theophylline, or dexamethasone to stimulate [ 14 C]pantothenate conversion to CoA was not decreased by the addition of ethanol or acetaldehyde, indicating that ethanol inhibition does not occur by reversal of the cAMP-mediated regulatory mechanism for CoA biosynthesis.