Pantothenic acid – vitamin B5 – was first discovered as an essential growth factor of yeasts, and later as a growth factor for lactic acid bacteria, chicks, and rats. Because of this ubiquitous occurrence, the substance was given the name pantothenic acid. The term “pantothene” comes from the Greek – pantos = everywhere. Pantothenic acid belongs to the water-soluble vitamins of the B-complex and chemically it is a dipeptide consisting of the aliphatic amino acid beta-alanine and the butyric acid derivative pantoic acid, which cannot be synthesized in the human cell. Beta-alanine and pantoic acid or 2,4-dihydroxy-3,3-dimethylbutyrate are linked by a peptide bond. In addition to the acid, the alcohol corresponding to D-pantothenic acid, R-pantothenol – identical to D-panthenol – is also biologically active. It can be oxidized to pantothenic acid and has about 80% of the biological activity of pantothenic acid. The S-forms of pantothenic acid and panthenol, respectively, have no vitamin activity. D-pantothenic acid is an unstable, highly hygroscopic, pale yellow, viscous oil. Due to its instability, sodium D-pantothenate, calcium D-pantothenate, and D-panthenol are mostly added to dietary foods and supplements and used for food fortification. Pantothenic acid exerts its effects in plant, animal, and human organisms exclusively in the form of coenzyme A (CoA) and 4́-phosphopantetheine, an essential component of fatty acid synthase.
- Coenzyme A is involved in numerous metabolic reactions and is composed of several components. These include cysteamine – also thioethanolamine -, D-pantothenic acid, diphosphate, adenine, and ribose-3́-phosphate. If we consider pantothenic acid together with cysteamine, we speak of pantheine. The diphosphate, together with the 3́-phospho-adenosine, can be thought of as 3́-phospho-adenosine diphosphate. Finally, coenzyme A consists of panthetein and 3́-phospho-ADP.
- If a phosphate residue of the coenzyme A molecule is added to the panthetein, 4́-phosphopantetheine is formed. The latter represents the prosthetic group of fatty acid synthase, meaning that 4́-phosphopantetheine is tightly bound to the enzyme. Fatty acid synthase is a multienzyme complex for the synthesis of saturated fatty acids. It has an acyl carrier protein (ACP) with two major sulfide functional groups, a peripheral SH group formed by a cysteinyl residue and a central SH group derived from 4́-phosphopantetheine.
Occurrence and availability
As the name suggests, pantothenic acid is widely distributed in nature. It is formed by green plants and most microorganisms, but not by the organism of higher animals. In plant and animal tissues, 50 to 95% is present in the form of coenzyme A and 4́-phosphopantetheine. Vitamin B5 is present in practically all plant and animal foods. Particularly rich in pantothenic acid are the royal jelly of bees and the ovaries (ovaries) of stockfish. Because pantothenic acid is water-soluble and heat-sensitive, losses can occur during food preparation. Heating leads to cleavage of the vitamin into beta-alanine and pantoic acid or their lactone, respectively. Losses of between 20 and 70 % must be expected during both heating and preservation of meat and vegetables. Larger losses of pantothenic acid occur especially in alkaline and acidic environments and during thawing of frozen meat.
Absorption
Dietary pantothenic acid is absorbed essentially in bound form, predominantly as a component of coenzyme A and fatty acid synthase. Absorption of these compounds is not possible. For this reason, coenzyme A and the enzyme that forms saturated fatty acids are cleaved in the lumen of the stomach and intestine via the intermediate pantetheine to form free pantothenic acid and phosphoric acid esters. Throughout the small intestine, both pantetheine and free pantothenic acid are absorbed by passive diffusion into the enterocytes of the small intestinal mucosa (small intestinal mucosa). Pantothenic acid can also be actively absorbed by sodium-dependent cotransport. The final degradation of pantetheine to pantothenic acid occurs in the enterocytes.The alcohol panthenol, applied to the skin or administered orally, can also be passively absorbed. In the cells of the intestinal mucosa, panthenol is oxidized to pantothenic acid by enzymes.
Transport and distribution in the body
From enterocytes in the intestinal mucosa, pantothenic acid enters the blood and lymphatic pathways, where the vitamin is transported directly to target tissues bound to proteins and absorbed into cells. Uptake from plasma into cells occurs largely via active sodium-dependent cotransport. Specific storage organs for vitamin B5 are not known. However, higher tissue concentrations of pantothenic acid are found in cardiac muscle, kidneys, adrenal glands, and liver.
Metabolism
To prevent rapid loss by the kidneys, pantothenic acid undergoes rapid intracellular conversion to its active forms, 4́-phosphopantetheine and coenzyme A. The first step in coenzyme A synthesis occurs by the enzyme pantothenate kinase. This enzyme phosphorylates pantothenic acid to 4́-phosphopantothenic acid with the help of the energy carrier ATP – adenosine triphosphate. The phosphorylated acid is then amidated with the amino acid L-cysteine to form 4́-phosphopantothenylcysteine and converted to 4́-phosphopantetheine by a decarboxylation reaction. Condensation with the nucleotide residue of ATP leads to dephospho coenzyme A, which is ultimately built up to the final coenzyme A by the addition of another phosphate group. Coenzyme A now enters intermediary metabolism as a universal carrier of acyl groups. Acyls are radicals or functional groups derived from organic acids. These include, for example, the acetyl radical of acetic acid and the aminoacyl residues derived from amino acids. The 4́-phosphopantetheine residue of coenzyme A is used to build up fatty acid synthase. For this purpose, it is transferred to the hydroxyl – OH group of a serine residue of the enzyme for fatty acid synthesis. The 4́-phosphopantetheine forms the central SH group of fatty acid synthase and thus plays the role of the coenzyme.
Degradation and excretion
Coenzyme A is 95% localized in the mitochondria – cell organelles for ATP synthesis. There, pantothenic acid is released from coenzyme A via several hydrolytic steps in a reversal of biosynthesis. The final step in coenzyme A degradation is the cleavage of panthetein, which yields free pantothenic acid and cysteamine. Pantothenic acid is not degraded in the organism, but is excreted unchanged or in the form of 4́-phosphopantothenate. Orally supplied vitamin B5 appears 60-70% in the urine and 30-40% in the stool. If pantothenic acid was injected intravenously, almost the entire amount is detectable in the urine within 24 hours. Excess ingested pantothenic acid is largely excreted in the urine via the kidney. There is a close correlation between the amount of vitamin B5 ingested and excreted.