Pantothenate from tissues

Pantothenate in blood and tissues is bound (R9) and released by autolysis or hydrolysis. More vitamin could be released by use of an alkaline phosphatase and an enzyme from avian liver (L6). This method liberates pantothenate from coenzyme A in a variety of foods and tissues (N3, N4). A comparison of hydrolytic methods in blood suggested autolysis to be the most advantageous method (N3) in our hands, treatment with Clarase gave more reliable results as compared with autolysis, acid hydrolysis, treatment with Mylase P, or combination of Clarase and papain, or liver enzyme and alkaline phosphatase. In urine, pantothenic acid is unbound our results show no increase with Clarase treatment. The vitamin has presumably a low threshold. Pantothenic acid shows the same concentration in blood and cerebrospinal fluid. 

Enzyme hydrolysis, with papain, diastase, clarase, takadiastase, intestinal phosphatase, or combinations thereof is most commonly used to release pantothenate from food proteins (186). A cold perchloric acid extraction was used to release pantothenic acid from tissue samples (187). Food spoilage prior to analysis may lead to inflated pantothenic acid levels (19). 

Unlike several other B vitamin precursors of cofactors, pantothenate is not entirely converted to coenzyme forms inside the cell, and metabolic trapping is therefore less dominant than it is for some other B vitamins. There is some evidence that the free pantothenate in tissues is more closely related to dietary pantothenate than the coenzyme forms are the latter are relatively protected during periods of dietary deficiency or of low intakes. Uptake of pantothenate from plasma into most tissues is proportional to the plasma concentration because the active transport process is nowhere near saturated at typical plasma concentrations of c. 10 M. 

As the liberatioh of pantothenate from organisms or tissues is a necessary preliminary to study of their content of the substance, the required conditions have been investigated in some detail with animal tissues and foodstuffs The application of certain of these methods to microorgan sms has been examined and found satisfactory (73,114 see also 43). 

All tissues are capable of forming CoA from pantothenic acid, by the pathway shown in Figure 12.2 (Tahiliani and Beinlich, 1991 Begley et al., 2001). The first three enzymes catalyzing the formation of phosphopantetheine from pantothenic acid are found only in the cytosol. Although phosphopantetheine crosses the mitochondrial irmer membrane, CoA does not, but must be synthesized in situ. 

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. 

The serum level of pantothenic add is about 1 to 5 lM (Lopaschuk d ai, 1987). The vitamin in the bloodstream is transported into various tissues, where it is then converted to coenzyme A. Coenzyme A is synthesized from pantothenic add, ATP, and cysteine. The pathway of coenzyme A synthesis is shown in Figure 9,77. The cofactor of fatty add synthase is synthesized from coenzyme A and does not involve the direct participation of pantothenic acid. A specific enzyme catalyzes... 

A deficiency purely m pantothenic acid has probably never occurred, except Ln controlled studies. Persons suffering from severe malnutrition would be expected to be deficient in the vitamin. Studies with animals have shown that consumption of a diet deficient in the vitamin results in a loss of appetite, slow growth, skin lesions, ulceration of the intestines, weakness, and eventually death. Pantothenic acid deficiency also results in the production of gray fur in animals whose fur is colored. Biochemical studies with deficient animals have revealed severe de-creasesinpantothenicacidlevelsina variety of tissues, bu I only m (xlera le declines in the levels of coenzyme A in liver and kidney and maintenance of coenzyme A levels Ln the brain Smith t ai, 1987), Some striking defects in glycogen and ketone bc dy metabolism have been noted in pantothenic acid-deficient animals. 

Pantothenic acid is a structural component, but not the active site, of coenzyme A The acyl thiol esters form on the mercaptan moiety that originates from a cysteine (Fig. 8.39). The biosynthesis of coenzyme A occurs in the tissues requiring it. Because coenzyme A is required for nearly all acyl transfers, biosynthesis takes place in nearly all cells. 

The answer is e. (Murray, pp 627-661. Sciiver, pp 3897-3964. Sack, pp 121-138. Wilson, pp 287-320.) Ascorbic acid (vitamin C) is found in fresh fruits and vegetables. Deficiency of ascorbic acid produces scurvy, the sailor s disease. Ascorbic acid is necessary for the hydroxylation of proline to hydroxyproline in collagen, a process required in the formation and maintenance of connective tissue. The failure of mesenchymal cells to form collagen causes the skeletal, dental, and connective tissue deterioration seen in scurvy. Thiamine, niacin, cobalamin, and pantothenic acid can all be obtained from fish or meat products. The nomenclature of vitamins began by classifying fat-soluble vitamins as A (followed by subsequent letters of the alphabet such as D, E, and K) and water-soluble vitamins as B. Components of the B vitamin fraction were then given subscripts, e.g., thiamine (Bi), riboflavin (B2), niacin [nicotinic acid (B3)], panthothenic acid (B5), pyridoxine (Bg), and cobalamin (B ). The water-soluble vitamins C, biotin, and folic acid do not follow the B nomenclature. 

Pantothenic Acid. (R)-V-r2>4-Dihydroxy-3,3-di-methyl-l-oxobutyll-B -alanine D(+)-/V-(2,4-dihydroxy-3,3-dimethy1butyryl)-d-alanine chick antidermatitis factor. C--HjjNO, mol wt 219.23, C 49.30%, H 7.82%, N 6.39%, O 36.49%, A member of the B complex vitamins. Occurs everywhere in animal and plant tissue. The richest common source is liver, but jelly of the queen bee contains 6 times as much as liver. Rice bran and molasses are other good sources. Isoln from liver R. J. Williams ei at, J. Am. 

Sample preparation should liberate the vitamin from the matrix, e.g., tissue or plasma, where it often occurs chemically or physically bound. Many specific transport binding proteins are known, e.g., for retinol. Chemical bonding can include the incorporation of a vitamin into coenzymes, e.g., niacin and pantothenate in NAD and coenzyme A, respectively. Liberating vitamins from industrial product forms (formulations) is also an important issue. Here, vitamins are often encapsulated in small beadlets, e.g., from gelatin, which protects them from oxygen and makes them easier to add during processing. 

The biochemical role of pantothenic acid is intimately associated with that of coenzyme A (see Fig. 4-12). The role and mode of action of the coenzyme have been considered in other chapters. Thus, it is logical to assume that the morphological alterations in the different tissues result from interference with reactions requiring coenzyme A. 

The most reasonable interpretation of the extremely diverse effects resulting from pantothenic acid deficiency in various animals (and humans) is based upon the supposition that each tissue in the body is capable of being nourished at various levels of efficiency, and that pantothenic deficiency which can potentially cause damage in every tissue, strikes sometimes here and sometimes there, depending upon many factors which reside in the species or in the afflicted individual animal. Despite the absence of any well-defined human deficiency syndrome there can be no intelligent question regarding the importance of pantothenic acid in human nutrition. 

All tissues are capable of forming coenzyme A from pantothenic acid. CoA functions as the carrier of fatty acids, as thioesters, in mitochondrial P-oxidation (section 5.5.2). The resultant two-carbon fragments, as acetyl CoA, then undergo oxidation in the citric acid cycle (section 5.4.4). CoA also functions as a carrier in the transfer of acetyl (and other fatty acyl) moieties in a variety of biosynthetic and catabolic reactions, including ... 

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