Vitamin Phosphate Esters

Phosphate esters of a-tocopherol (vitamin E) (12.141a) and retinol phosphate (vitamin A phosphate) (12.141b) and their derivatives are used in cosmetics and skin care preparations [49]. 

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In humans, thiamine is both actively and passively absorbed to a limited level in the intestines, is transported as the free vitamin, is then taken up in actively metabolizing tissues, and is converted to the phosphate esters via ubiquitous thiamine kinases. During thiamine deficiency all tissues stores are readily mobilhed. Because depletion of thiamine levels in erythrocytes parallels that of other tissues, erythrocyte thiamine levels ate used to quantitate severity of the deficiency. As deficiency progresses, thiamine becomes indetectable in the urine, the primary excretory route for this vitamin and its metaboHtes. Six major metaboHtes, of more than 20 total, have been characterized from human urine, including thiamine fragments (7,8), and the corresponding carboxyHc acids (1,37,38). 

Elimination usually involves loss of a proton together with a nucleophilic group such as -OH, -NH3+, phosphate, or pyrophosphate. However, as in Eq. 13-18, step c, electrophilic groups such as -COO-can replace the proton. Another example is the conversion of mevalonic acid-5-pyrophosphate to isopentenyl pyrophosphate (Eq. 13-19) This is a key reaction in the biosynthesis of isoprenoid compounds such as cholesterol and vitamin A (Chapter 22). The phosphate ester formed in step a is a probable intermediate and the reaction probably involves a carbo-cationic intermediate generated by the loss of phosphate prior to the decarboxylation. 

The phosphate ester of the aldehyde form of vitamin B6, pyridoxal phosphate (pyridoxal-P or PLP), is required by many enzymes catalyzing reactions of amino acids and amines. The reactions are numerous, and pyridoxal phosphate is surely one of nature s most versatile catalysts. The story begins with biochemical transamination, a process of central importance in nitrogen metabolism. In 1937, Alexander Braunstein and Maria Kritzmann, in Moscow, described the transamination reaction by which amino groups can be transferred from one carbon skeleton to another.139 140 For example, the amino group of glutamate can be transferred to the carbon skeleton of oxaloacetate to form aspartate and 2-oxoglutarate (Eq. 14-24). 

Synthesis of inositol by animals is limited and n/i/o-inositol is sometimes classified as a vitamin. Mice grow poorly and lose some of their hair if deprived of dietary inositol. Various phosphate esters of inositol... 

The six principal B6 vitamers are widely distributed in foods (102,103). They include pyridoxine (PN), pyridoxal (PL), pyridoxamine (PM), and their 5 -phosphate esters, pyridoxine phosphate (PNP), pyridoxal phosphate (PLP), and pyridoxamine phosphate (PMP) (Fig. 5). The predominate B6 vitamer in animal-based foods is PLP, whereas plant products generally contain PN and PM or their phosphorylated forms. Conjugated vitamers in the form of PN-glycosides have also been isolated from plant-based foods. Pyridoxal is readily converted to PM during cooking and food processing. Total vitamin B6 is the sum of the six principal vitamers inclusion of the conjugated forms depends on the extraction procedure. 

There are various physiological forms known as vitamins D, namely vitamin D2 (calciferol, ergocaldferol), vitamin D3 (cholecalciferol), phosphate esters of D2, D3, 25-hydroxycholecalciferol, 1,25-dihydroxychole-caldferol, and 5,25-dihydroxycholecalciferol. There are active anologs and related compounds known as vitamins D, namely 22-dihydroergosterol (vitamin D4), 2-dehydrostigmasterol (vitamin Dg), and 7-dehydro-sitosterol (vitamin D5) [3]. 

There are different physiological forms known as vitamins E, namely d-a-tocopherol, tocopheronolactone, and their phosphate esters. There are active analogs and related compounds knows as vitamins E, namely d/-atocopherol, /-a-tocopherol, esters (succinate, acetate, phosphate), and j8-, 1-, j-tocopherols [3]. 

The vitamin is commercially available as riboflavin, riboflavin S-phosphate. and riboflavin S-phosphate sodium. The phosphate esters are used commercially only in multivitamin preparations, and they are hydrolyzed before absorption occurs. Ab.sorption occurs through an active transport. system in which riboflavin is phosphorylated by the intestinal mucosa during absorption. Food and bile enhance absorption. Riboflavin is distributed widely in the body, with limited stores in the liver, spleen, heart, and kidneys. Conversion to FAD occurs primarily in the liver. FMN and FAD circulate primarily protein bound. Only small amounts ( 9%) are excreted in the urine unchanged. Larger amounts can be found after administration of large doses. 

Hydroxocobalamin, USP. Hydroxixtobalamin, cobi-namidc dihydroxide, dihydrogen phosphate (ester) munu(in-ner salt), 3 -ester with, 3,6-dimethyl-1-ff-n-ribofuranosyl-bcnzimidazole. vitamin B 2i>< >s cyanocobalamin in which the CN group is replaced by an OH group. It occurs as dark... 

Analogously, ethyl 4-fluoro-3-methylcrotonate is brominated with NBS in the presence of AIBN and then reacted with triethyl phosphite to produce good yields (72-78%) of a-fluorophosphonate, a key intermediate in the synthesis of fluorinated vitamin A esters (Scheme 3.3)7 Following a similar procedure (radical bromination and Michaelis-Arbuzov rearrangement), ( )-l-fluoro-3-(l-trityl-l,2,4-triazol-3-yl)-2-propenylphosphonate, a good inhibitor of imidazoleglycerol phosphate dehydratase, has been prepared in 25% overall yield. ... 

For coagulant activity the isoprenoid side chains are not mandatory. Thus menadione, which is a naphthaquinone carrying only a methyl group at the 3-position, is considered a synthetic K vitamin (K3). It has the same actions as the natural products. It, and two derivatives—the water-soluble sodium bisulfite addition compound and the disodium salt of the phosphate ester of reduced menadione—are all used clinically as hemostatics, and to antidote overdoses of anticoagulants. 

The catabolic pathway of vitamin Bg (1) is probably the best studied. In animals (including humans) 4-pyridoxic acid (4) is the primary catabolic product of vitamin Bg, found in urine. It is formed by the oxidation of pyridoxal (2) by a nonspecific flavin adenine dinucleotide (FAD)-dependent aldehyde oxidase. The catalytically active form of vitamin Bg, pyridoxal-5 -phosphate, PLP (17), does not undergo similar oxidation to form 4. The various forms of vitamin Bg (1, 2, 15) and their respective phosphate esters (16, 17) are readily enzymatically interconvertible. Further degradation of 4 is unlikely in humans as the subjects administered with doses of 4 were found to excrete it quantitatively. Estimation of 4 in urine serves as a nutritional marker, as lower than normal amounts of 4 is indicative of vitamin Bg deficiency. ... 

Aquocobalamill. Cobinamide dihydroxide, mono-hydrate, dihydrogen phosphate ester, mono(t ner salt), 3 -esfer with 5,6-dimethyt-I-< -U-ribofuranosyi-1Il-benzimid-azote vitamin Bl2k aquocobamide a-(3,6-dimethylbenz-imidazolylhiquocobamide. 

Thiamine Triphosphoric Acid Ester, Thiamine tri -phosphate ester vitamin B, triphosphate ester. 

Vitamin B6 has been shown to be essential in many biochemical reactions that occur in plants and animals. Although it may occur in any one of the three forms listed above, the compound usually acts as the phosphate ester, pyridoxine phosphate. Pyridoxine phosphate functions as a coenzyme in the transformation of amino acids, the building blocks from which proteins are made. A coenzyme is a chemical compound that works with an enzyme to catalyze some essential chemical reaction in the body. Pyridoxine phosphate appears to be necessary for the synthesis of proteins from amino acids as well as the metabolism of amino acids to produce energy needed for normal body functioning. 

S. Miyamoto, T. Koga, and J. Terao Synthesis of a novel phosphate ester of a vitamin E derivative and its antioxidant activity. Bioscience, Biotechnology, and Biochemistry 62 (1998) 2463-2466. 

Vitamin Bg exists as six separate forms in the pyridine group of water-soluble vitamins. The common forms are pyridoxal and pyri-doxamine together with their corresponding phosphate esters and pyridoxine forms. These compounds function as cofactors in a wide variety of enzyme reactions, but most notably in the transamination reaction of amino acid biosynthetic pathways. Extraction of this group of vitamins can be performed by the same methods as those described for the B2 vitamins (Section 11.8.3.3). 

Reversed phase systems have been used to separate the different members of the vitamin Bg group and typical conditions employ a Cig stationary phase with a mobile phase of acetonitrile-aqueous phosphate buffer (Lim et al., 1980). Other popular methods are based on ion-exchange chromatography and a complete separation of pyri-doxamine, pyridoxal, pyridoxine and their phosphate esters has been... 

Synonyms Riboflavin monophosphate monosodium salt Riboflavin 5 -monophosphate sodium salt dihydrate Riboflavin 5 -phosphate ester monosodium salt Riboflavin 5 - (sodium hydrogen phosphate) Riboflavin sodium phosphate Sodium riboflavin phosphate (INCI) Vitamin B2 phosphate sodium... 

Vitamins, like pharmaceutical substances, can often be determined by UV absorption or electrochemical detection without derivatization. However, vitamins were detennined in a senri-automated manifold by post-column reaction with a coupling reaction with diazotized 5-chloroaniline-2,4-disulphonyl chloride and continuous colorimetric determination of the orange products at 440nm [211]. Post-column derivatization schemes for thiamine and its phosphate esters have also been described [212-214]. 

Thiamine (vitamin Bj) occurs in foods in free and bound forms, the free form predominates in cereals and plants, whereas the pyrophosphate ester is the main form in animal products. Acid hydrolysis is required to release thiamine from the food matrix. Enzymatic hydrolysis is then needed to convert phosphate esters to thiamine. Prior to CE analysis it is necessary to clean up samples by using ethanol to precipitate protein and by passing through an ion-exchange resin. Thiamine has been determined in meat and milk samples using MEKC with ultraviolet (UV) detection at 254 nm, obtaining comparable sensitivity to that achieved by HPLC using an ion-pair reversed-phase column with postcolumn derivat-ization and fluorescence detection. 

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