Pantothenic acid absorption

Pantothenic acid is taken in as dietary CoA compounds and dCphosphopantetheine and hydrolyzed by pyrophosphatase and phosphatase in the intestinal lumen to dephospho-CoA, phosphopantetheine, and pantetheine. This is further hydrolyzed to pantethenic acid. The vitamin is primarily absorbed as pantothenic acid by a saturable process at low concentrations and by simple diffusion at higher ones. The saturable process is facilitated by a sodium-dependent multivitamin transporter, for which biotin and lipoate compete. After absorption, pantothenic acid enters the circulation and is taken up by cells in a manner similar to its intestinal adsorption. The synthesis of CoA from pantothenate is regulated by pantothenate kinase, which itself is subject to negative feedback from the products CoA and acyi-CoA. The steps involved were outlined above. Pantothenic acid is excreted in the urine after hydrolysis of CoA compounds by enzymes that cleave phosphate and the cys-teamine moieties. Only a small fraction of pantothenate is secreted into milk and even less into colostrum. 

UV absorption occurs only below 220nm, thereby it is affected by the interference from mobile phase and from artifacts in complex foods. A multiwavelength UV detection has been experimented successfully for unambiguous evaluation of pantothenic acid [609]. However, UV detection presents a low sensitivity, compared to other techniques, like FLD or MS. FLD is applied by using a postcolumn derivatization. Pantothenic acid is converted to 3-alanine by hot alkaline hydrolysis and a reaction with OPA [610]. Also MS is successfully applied to increase the sensitivity of pantothenic acid analysis. 

The coenzymes, CoA, acyl-coenzyme A, and ACP, are the biologically active forms of pantothenic acid (185,186). Recent reviews of the absorption and metabolism of pantothenate are available (185,186). 

It should be noted that deficiency states for some vitamins (e.g., pantothenic acid) are practically unknown in human beings. In such cases, deficiency states may be simulated by feeding the subject an appropriate vitamin antagonist. In another series of situations, vitamin deficiencies can be brought about by interfering with their absorption intentionally or may be the result of a disease process. Thus, fat-soluble vitamin deficiency may develop in cases of fat malabsorption syndromes (steatorrhea) sprue, pancreatic insufficiency, and bile duct obstruction. 

The intestinal absorption of pantothenic acid is by use of the same sodium-dependent carrier as biotin and lipoic acid (Section 11.1). The carrier is found throughout the intestinal tract, and therefore pantothenic acid synthesized by intestinal bacteria (Section 12.2.4) will, like biotin, be available for absorption (Said et al., 1998 Chatterjee et al., 1999 Ramaswamy, 1999 Said, 1999 Prasad... 

Some itamirLS are water soluble, while others are fat soluble. This classification is valuable as it indicates whether the vitamin is likely to be absorbed similarly to lipids or like other water-soluble nutrients. The fat-soluble vitamins are A, D, E, and K. The water-soluble vitamins arc ascorbic acid, biotin, folate, niacin, pantothenic acid, riboflavin, thiamin, vitamin B i, and vitamin B 2. The classification is also valuable, as it helps chemists decide on the best way to extract and analyze a particular vitamin in foods and biological tissues. Aside from having some bearing on the path ways of absorption and distribution throughout the body, the question of whether a particular vitamin is fat soluble or water soluble has little or no relevance to its function in the body. 

Dietary pantothenic acid is consumed as coenzyme A and the intermediates from coenzyme As biosynthesis (Fig. 8.39). These are hydrolyzed to free pantothenic acid. Absorption is by saturable, active transport. 

About 85% of dietary pantothenic acid occurs as CoA or phosphopantetheine. In the intestinal lumen these are hydrolysed to pantetheine intestinal mucosal cells have a high pantetheinase activity and rapidly hydrolyse pantetheine to pantothenic acid. The intestinal absorption of pantothenic acid is by diffusion and occurs at a constant rate throughout the length of the small intestine intestinal bacterial synthesis may contribute to pantothenic acid nutrition. 

A similar quantitative analysis of six water-soluble vitamins (B, B2, Bg, C, nicotinamide, and pantothenic acid) in a pharmaceutical formulation using CZE in uncoated fused silica capillaries with UV detection was described by Fotsing et al. (91). Eor the B-group vitamins, a good compromise among resolution, analysis time, and analyte stability was obtained by use of 50 mM borax buffer pH 8.5. A capillary wash with sodium hydroxide was necessary between successive runs to minimize absorption of excipients from the pharmaceutical formulation to the capillary surface, otherwise giving rise to a progressive decrease of the electro-osmotic flow. 

Pantothenic acid and its salts as well as its degradation products such as pantoic acid and P-alanine do not exhibit significant absorption above 220 nm. As a result, the limitation of the direct HPLC assays lies in the lack of a selective detection wavelength. Detection is mainly performed by UV absorption at low wavelength. Analysis using UV detection below 220 nm has inherent problems because of the limited number of common mobile-phase solvents that have appropriate cutoff and because of dissolved oxygen that has to be removed via sonica-tion under vacuum. 

Pantothenic acid, also known as vitamin B5, is widely distributed in food, since it is a component in the coenzyme A structure. Therefore, it is essential to all organisms and its deficiency is imcommon. In addition, being part of this coenzyme, for the total vitamin B5 determination, an enzyme hydrolysis is necessary prior to analysis. Foods richest in pantothenic acid are organ meats, egg yolk, and whole grains. RP separations are employed to analyze pantothenic acid, which does not possess any specific UV—Vis absorption. To overcome this problem, either fluorescence detection or MS detection is employed. 

The UV—diode array [132,134—136,139,140] and fluorescence detection [141,142] have been used to develop multivitamin LC methods, which, however, remain limited to a few analytes responding to the same detection system and extracted quantitatively with the same procedure. Moreover, by means of a UV detector, other difficulties are represented by the absence of a strong chromophoric group in some vitamins (pantothenic acid and biotin), which absorb with modest sensitivity in the low UV region only, where the selectivity is scarce (absorption of interfering compoimds). 

Two biotin transporters have been described a multivitamin transporter present in many tissues and a biotin transporter identified in human lymphocytes. In 1997, Prasad and coworkers discovered a Na" "-coupled, saturable, structurally specific transporter present in human placental choriocarcinoma cells that can transport pantothenic acid, lipoic acid, and biotin. This sodium-dependent multivitamin transporter has been named SMVT and is widely expressed in human tissues. Studies by Said and coworkers using RNA interference specific for SMVT provide strong evidence that biotin uptake by Caco-2 and HepG2 cells occurs via SMVT thus, intestinal absorption and hepatic uptake are likely mediated by SMVT. The biotin transporter identified in lymphocytes is also Na coupled, saturable, and structurally specific. Studies by Zempleni and coworkers provide evidence in favor of monocarboxylate transporter-1 as the lymphocyte biotin transporter. 

In mice, it was found that usual dietary pantothenate levels did not affect the rate of absorption of a standard pantothenate dose, i.e., there was no evidence for feedback adaptation of the absorption pathway to low or high intakes, and it is assumed that the same is true in other species, including humans. However, there is some evidence from rat studies that the extent of secretion of enzymes degrading CoA into the gut lumen may partially limit the availability of pantothenic acid from CoA. 

---