The effect of pantothenic acid deficiency on keratinocyte proliferation and the synthesis of keratinocyte growth factor and collagen in fibroblasts.

It has been reported that pantothenic acid (vitamin B5) and panthenol, an alcohol derivative of pantothenic acid, have beneficial moisturizing effects on the skin. However, few studies have investigated the mechanism of action of pantothenic acid on skin tissues. We tried to clarify the role of pantothenic acid on skin function by using keratinocytes and fibroblasts. The depletion of pantothenic acid from the culture medium suppressed keratinocyte proliferation and promoted differentiation. Moreover, pantothenic acid depletion decreased the synthesis of keratinocyte growth factor and procollagen 4a2 in fibroblasts. These results suggest that pantothenic acid is essential for maintaining keratinocyte proliferation and differentiation.

Esmond E. Snell--the pathfinder of B vitamins and cofactors.

Esmond E. Snell (1914-2003) was a giant of B-vitamin and enzyme research. His early research in bacterial nutrition had lead to the discovery of vitamins such as lipoic acid and folic acid, and an anti-vitamin avidin. He developed microbiological assay methods for riboflavin and other vitamins and amino acids, which are still used today. He also investigated the metabolism of vitamins, discovered pyridoxal and pyridoxamine as the active forms of vitamin B(6) and revealed the mechanism of transamination and other reactions catalysed by vitamin B(6) enzymes. His research in later years on pyruvoyl-dependent histidine decarboxylase unveiled the biogenesis mechanism of this first built-in cofactor. Throughout his career, he was a great mentor of many people, all of whom are inspired by his philosophy of science.

Roles of vitamins B5, B8, B9, B12 and molybdenum cofactor at cellular and organismal levels.

Many efforts have been made in recent decades to understand how coenzymes, including vitamins, are synthesised in organisms. In the present review, we describe the most recent findings about the biological roles of five coenzymes: folate (vitamin B9), pantothenate (vitamin B5), cobalamin (vitamin B12), biotin (vitamin B8) and molybdenum cofactor (Moco). In the first part, we will emphasise their biological functions, including the specific roles found in some organisms. In the second part we will present some nutritional aspects and potential strategies to enhance the cofactor contents in organisms of interest.

Vitamins, minerals and supplements: part two.

Vitamins and minerals are organic food substances found only in plants and animals and are essential to the normal functioning of the body. Although only required in small amounts, as previously discussed in the past decade there has been an increased use of vitamin, mineral, herbal and nutritional supplements in the general population. While deficiencies in such nutrients can be harmful to health, conflicting claims have been made about the health benefits of such supplementation. In the second of an occasional series on vitamins, minerals, and supplements, JUNE THOMPSON gives an overview of the role that water-soluble vitamins play in the health of the individual, including their functions, and the potential impact of any deficiency of these.

[Coenzyme A biosynthesis as universal mechanism of conjugation of exogenous and multiple pantothenic acid functions]. / Biosintez kofermenta A--universal'nyi mekhanizm sopriazheniia ékzogennosti i mnozhestvennosti funktsii pantotenovoi kisloty.

Development of Academician R. V. Chagovets' ideas of the regulatory role of vitamins and their derivatives in thiol-containing compound metabolism and antioxidant system formation as well as in studying non-coenzymatic functions of B-vitamins and vitamin-binding proteins had a considerable effect on the almost 40-year studies on pantothenic acid metabolism and biochemical functions by scholars at the vitaminologic school in Grodno. The concept concerning the intracellular structure of the pantothenate coenzyme form, CoA, pool (content and ratio of CoA-SH, acetyl-CoA, short-chain and long-chain acyls-CoA, coenzyme disulfide forms and CoA-S-S-proteins) was substantiated as an important metabolic regulatory factor (including glutathione system redox potential), with changes being a principal mechanism of pantothenate derivative vitamin and pharmacotherapeutic activity implementation. The effect of the latter is mediated through the systems of CoA biosynthesis and phosphopantetheine proteins, changed CoA-S-S-protein levels, which in turn maintain the intracellular level of CoA-SH as well as cytosolic and mitochondrial transport of its vitamin-containing precursors. A universal CoA biosynthetic function was revealed in prevention of lipid peroxidation initiation and oxidative stress development.

[Pantothenic acid].

Pantothenic acid is the antipellagra vitamin essential to many animals for growth and health. It is widely distributed in nature; appreciable amounts are found in liver and some microorganisms. Bound forms of pantothenic acid, such as coenzyme A and 4'-phosphopantetheine, play important roles in various metabolic processes, especially, in fatty acid synthesis and degradation.

Mutations in sdh (succinate dehydrogenase genes) alter the thiamine requirement of Salmonella typhimurium.

Mutants lacking the first enzyme in de novo purine synthesis (PurF) can synthesize thiamine if increased levels of pantothenate are present in the culture medium (J. L. Enos-Berlage and D. M. Downs, J. Bacteriol. 178:1476-1479, 1996). Derivatives of purF mutants that no longer required pantothenate for thiamine-independent growth were isolated. Analysis of these mutants demonstrated that they were defective in succinate dehydrogenase (Sdh), an enzyme of the tricarboxylic acid cycle. Results of phenotypic analyses suggested that a defect in Sdh decreased the thiamine requirement of Salmonella typhimurium. This reduced requirement correlated with levels of succinyl-coenzyme A (succinyl-CoA), which is synthesized in a thiamine pyrophosphate-dependent reaction. The effect of succinyl-CoA on thiamine metabolism was distinct from the role of pantothenate in thiamine synthesis.

Pantothenic acid in health and disease.

In summary, the vitamin pantothenic acid is an integral part of the acylation carriers, CoA and acyl carrier protein (ACP). The vitamin is readily available from diverse dietary sources, a fact which is underscored by the difficulty encountered in attempting to induce pantothenate deficiency. Although pantothenic acid deficiency has not been linked with any particular disease, deficiency of the vitamin results in generalized malaise clinically. In view of the fact that pantothenate is required for the synthesis of CoA, it is surprising that tissue CoA levels are not altered in pantothenate deficiency. This suggests that the cell is equipped to conserve its pantothenate content, possibly by a recycling mechanism for utilizing pantothenate obtained from degradation of pantothenate-containing molecules. Although the steps involved in the conversion of pantothenate to CoA have been characterized, much remains to be done to understand the regulation of CoA synthesis. In particular, in view of what is known about the in vitro regulation of pantothenate kinase, it is surprising that the enzyme is active in vivo, since factors that are known to inhibit the enzyme are present in excess of the concentrations known to inhibit the enzyme. Thus, other physiological regulatory factors (which are largely unknown) must counteract the effects of these inhibitors, since the pantothenate-to-CoA conversion is operative in vivo. Another step in the biosynthetic pathway that may be rate limiting is the conversion of 4'-phosphopantetheine (4'-PP) to dephospho-CoA, a step catalyzed by 4'-phosphopantetheine adenylyl-transferase. In mammalian systems, this step may occur in the mitochondria or in the cytosol. The teleological significance of these two pathways remains to be established, particularly since mitochondria are capable of transporting CoA from the cytosol. Altered homeostasis of CoA has been observed in diverse disease states including starvation, diabetes, alcoholism, Reye syndrome (RS), medium-chain acyl CoA dehydrogenase deficiency, vitamin B12 deficiency, and certain tumors. Hormones, such as glucocorticoids, insulin, and glucagon, as well as drugs, such as clofibrate, also affect tissue CoA levels. It is not known whether the abnormal metabolism observed in these conditions is the result of altered CoA metabolism or whether CoA levels change in response to hormonal or nonhormonal perturbations brought about in these conditions. In other words, a cause-effect relation remains to be elucidated. It is also not known whether the altered CoA metabolism (be it cause or result of abnormal metabolism) can be implicated in the manifestations of a disease. Besides CoA, pantothenic acid is also an integral part of the ACP molecule.(ABSTRACT TRUNCATED AT 400 WORDS)

[The role of riboflavin and pantothenic acid in the reproductive function of swine]. / Rol' riboflavina i pantotenovoi kisloty v reproduktivnoi funktsii svinei.

Results of the experiment have shown that in order to increase multiple pregnancy and quality of piglets the ration of sows during pubescence and in the reproductive period must contain not less than 5-6 mg of riboflavin and 20-22 mg of pantothenic acid per one feed unit. That level can be ensured either by addition of synthetic preparation of riboflavin (4-4.5 mg) and calcium d-pantothenate (10-15 mg), or by inclusion of about 5% of the fodder yeast mass into complete-ration combined feed.

Role of pantothenic and ascorbic acid in wound healing processes: in vitro study on fibroblasts.

In order to analyze the possible role of pantothenic acid (PA) and ascorbic acid (AA) in wound healing processes, the effects of these vitamins upon the growth of fibroblasts, obtained from human fetal skin or foreskin, were studied. Cell proliferation, protein synthesis and protein release were evaluated. The rate of cell growth remained identical when PA or AA were added to the culture medium. PA increased the basal incorporation of 14C proline into precipitated material while AA did not modify this action. However, when cultures were incubated with PA and AA, the release of intracellular protein into the culture medium increased. These results suggest that the combined use of these two vitamins might be of interest in postsurgical therapy and in wound healing.

Effects of homopantothenic acid on intestinal smooth muscles.

The effects of homopantothenic acid (HOPA) on intestinal smooth muscles were investigated and compared with those of gamma-aminobutyric acid (GABA). HOPA contracted the rat ileum and produced a biphasic response (relaxation followed by contraction) in the guinea-pig ileum and taenia coli. Half-maximal effects were obtained with 0.3-0.9 nM HOPA and maximal responses with 2-4 nM in the rat and the guinea-pig ileum. In the guinea-pig taenia, half-maximal effects were obtained with 0.2-0.25 microM HOPA and maximal responses with 2-4 microM HOPA. Tachyphylaxis occurred with higher concentrations. All these responses were not significantly affected by tetrodotoxin (TTX), atropine, diphenhydramine or metiamide. The relaxation elicited by HOPA was not reduced by simultaneous application of phentolamine and propranolol. Unlike HOPA, GABA produced a biphasic response (a relaxation followed by a contraction) in the guinea-pig ileum, which was almost abolished by TTX. These results suggest that HOPA mainly acts on intestinal smooth muscle directly, whereas GABA does indirectly through nerves.

Vitamins and lipid metabolism.

Vitamins play an essential role in lipid metabolism reactions and their presence is therefore absolutely necessary for these reaction to occur. The effect of pantothenic acid, niacin and riboflavin is here described. By transformation into coenzymes these vitamins are involved in fatty acid synthesis and oxidation reactions. Other vitamins, like vitamin B12, folic acid, vitamin C, and essential fatty acids influence lipid metabolism by different mechanisms. Coenzyme B12 and folate coenzyme provide to balance, by methionine synthesis, the pool of methyl radicals necessary for phospholipid biosynthesis. By its involvement in the microsomal respiratory chain, vitamin C promotes cholesterol transformation into bile acids. The essential fatty acids, mainly linoleic acid, are directly connected with cholesterol transport and plasma cholesterol decrease. It is suggested that many lipid metabolism disorders may be due to primary and secondary hypovitaminosis. Nicotinic acid and its derivatives have a particular pharmacological effect since they cause a HDL increase with LDL decrease and improve cholesterol transfer from LDL to HDL. Results of several experiments on the influence of pantothenic acid on polyunsaturated fatty acid metabolism are eventually reported, and these data are related to the effect of the administration of vitamin C at high doses on total cholesterol, triglyceride, lipoprotein, vitamin C and fatty acids of the different plasma lipid fractions.

Role of placenta in maternal-fetal vitamin transfer in humans.

Vitamins B12, B6, biotin, folate, thiamine, riboflavin, pantothenate, and nicotinate were determined in maternal and fetal blood and placental tissue of normovitaminemic and hypovitaminemic mothers who disclaimed supplemental vitamin intake during pregnancy. No biotin or pantothenate deficits were observed in the gravidas. Hypovitaminemic mothers transferred less B12, folate, and B6 to the fetus and placenta than normovitaminemic mothers. Vitamins given by mouth increased maternal fetal, and placental levels of folate, but B6 increased only in maternal blood and the placenta; biotin and pantothenate increased only in fetal blood. Except for riboflavin, nicotinate, and pantothenate, the intramuscular administration of vitamins increased the levels of other vitamins in maternal and fetal blood and placental tissue. Results suggest that the placenta stores vitamins and the tissue vitamin receptors must be saturated before adequate transfer of vitamins to the fetus occurs.