The Metabolic Functions of Vitamin

The main metabolic function of vitamin K is as the coenzyme in the carboxyla-tion of protein-incorporated gluteimate residues to yield / -ceirboxygluteLmate -a unique type of ceirboxylation reaction, clearly distinct from the biotin-dependent carboxylation reactions (Section 11.2.1). 

In addition to blood clotting, y-cai boxyglutamate-containing proteins ai e found in 

the kidney cortex (nephrocEilcin) hydroxyapatite and ceilcium oxalate containing urinary stones  

atherosclerotic plaque - this protein is sometimes called atherocEilcin, but is probably the same as the bone matrix Gla protein (Section 5.5.3.3)  

the intermembrane space of mitochondria, where they may have a role in the mitochondrial accumulation of ceilcium and 

The quinone ring is derived from isochorismic acid, formed by isomerization of chorismic acid, an intermediate in the shikirnic acid pathway for synthesis of the aromatic amino acids. The first intermediate unique to menaquinone formation is o-succinyl benzoate, which is formed by a thiamin pyrophosphate-dependent condensation between 2-oxoglutarate and chorismic acid. The reaction catalyzed by o-succinylbenzoate synthetase is a complex one, involving initially the formation of the succinic semialdehyde-thiamin diphosphate complex by decarboxylation of 2-oxoglutarate, then addition of the succinyl moiety to isochorismate, followed by removal of the pyruvoyl side chain and the hydroxyl group of isochorismate. 

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The medicinal chemistry of vitamins is fundamental not only to the therapeutics of nutritional problems but also to the understanding of the biochemical actions of other medicinal agents that directly or indirectly affect the metabolic functions of vitamins and coenzymes. Accordingly, this chapter includes a brief sununary of the basic biochemislry of vitamins, structure-activity relationships, physicochemical properties and some stability considerations, nutritional and therapeutic applications, and brief characterizations of repre.sentative pharmaceutical products. 

The main function of vitamin D is in the control of calcium homeostasis, and in mrn vitamin D metabolism is... 

The metabolic significance of vitamin Bg and its role to the growth and functional development have been published (67-78). 

The manifold relationships between the metabolic functions of the liver and the vitamins fulfil vital tasks in helping the organism to stay healthy. Nutrition low in vitamins or age-related reduction in intestinal vitamin resorption as well as chronic alcoholism may be responsible for the development of hypovitaminosis. Standard values of vitamins (including fat-soluble vitamins) in the serum do not exclude a deficit. Deficiency is often recognized for the first time owing to the manifestation of clinical symptoms, and now requires substitution. Substitution therapy may be recommended, even if no vitamin deficiencies have become manifest at this stage, (s. p. 47) (s. tab. 28.2 )... 

The assay for serum Bn levels is a direct lest, as it measures the concentration of the vitamin itself. The assay of MM A levels is a functional test of B12 status, as it measures a compound whose metabolism is dependent on the correct functioning of vitamin Bn- The results of the MMA test reflect the activity of methylmalonyl-CoA mutase in the liver It is thought that the functional test is more valuable than the direct test. Serum vitamin Bij levels may not reflect the functioning of the B j-requiring enzymes of the cell. Serum Bii levels may sometimes be withm the normal range despite an increased excretion of MMA. Normal scrum Bt2 values range from 0.2 to 1,0 ng/ml. Normal serum MMA levels range from 20 to 75 ng/ml, and normal urinary MMA levels from 0,6 to 3-0 pg/ml. 

In higher mammals, riboflavin is absorbed readily from the intestines and distributed to all tis.sues. It is the precursor in the biosynthesis of the cocnzyme.s flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). The metabolic functions of this vitamin involve these Iwocoenzymes. which participate in numerous vital oxidation-reduction proces.ses. FMN (riboflavin 5 -phosphate) is produced from the vitamin and ATP by flavokinasc catalysis. This step con be inhibited by phcnothiazincs and the tricyclic antidepressants. FAD originates from an FMN and ATP reaction that involves reversible dinucicotide formation catalyzed by flavin nucleotide pyrophosphorylase. The.se coenzymes function in combination with several enzymes as coenzyme-en-zyme complexes, often characterized as, flavoproteins. 

The action of vitamin D in human and animal organisms is primarily related to calcium metabolism and the mineralization of bones and teeth, although the mechanism of these processes has not yet been unequivocally confirmed. The cooperation of vitamins A and K is necessary for the proper functioning of vitamin... 

The main function of vitamin B12 is thought to be in the metabolism of amino acids. Thus, B,2 is involved in the conversion of homocysteine to methionine and in the catabolism of some branched-chain amino acids. The neurological disorder that is usually associated with vitamin B12 deficiency is due to progressive demyelination of nervous tissue, thought to be owing to a build up of the vitamin Bj2 substrate, methylmalonyl CoA. This probably interferes with the formation of the myelin sheath. 

Vitamin Bg has a crucial role in 1-carbon metabolism, which involves DNA synthesis and DNA methylation, and can modulate gene expression. Electrochemical and spectroscopic studies (Liu et al. 2008) have shown that vitamin Bg can interact with DNA. These findings are helpful in understanding the biological functions of vitamin Bg. 

Vitamin Bs consists of six forms in nature, i.e. pyridoxine (PN), pyridoxal (PL), pyridoxamine (PM), pyridoxine 5 -phosphate (PNP), pyridoxal 5 -phosphate (PLP), and pyridoxamine 5 -phosphate (PMP) (Figure 22.1). PLP is a coenzyme for many enzymes involved in amino acid and carbohydrate metabolism, and plays a key role in the nutritional function of vitamin Bg. The other forms show the same nutritional efficiency because they are converted into PLP in cells. The free forms of vitamin Bg are adsorbed through the intestinal mucosa, and then are phosphorylated and converted into PLP in the liver. Some PLP exits the liver and travels in the blood on albumin, being turned over slowly. PL is the form most actively transported to other cells from the liver. The cells adsorb PL and then phosphorylate it to yield PLP. The final metabolite derived from vitamin Bg is 4-pyridoxic acid (4-PA, Figure 22.1), which is excreted into the urine. Plants contain a storage form of vitamin Bg, pyridoxine-p-glucoside... 

The presence of pantothenic acid in this coenzyme and the fact that most, if not all, cellular bound pantothenate is in the form of the coenzyme explain the metabolic function of this vitamin. 

Green et al. (1956) determined the vitamin K content of the liver cell particulates by the biological method, using vitamin K-deficient chicks. Of the total amount, 61 % was found in the mitochondria fraction, 24 % in the nucleus, and 15 % in the supernatant, the calculation being based on the nitrogen content of the fractions. Considering the metabolic function of... 

The main function of vitamin D is in the control of calcium homeostasis (section 11.15.1) and, in turn, vitamin D metabolism is regulated, at the level of 1- or 24-hydroxylation, by factors that respond to plasma concentrations of calcium and phosphate ... 

Vitamin D can be viewed as a prohormone which arises by the action of ultraviolet light in the two-step process pictured in Fig. 20. Irradiation of 7-dehydrocholesterol in the skin can provide adequate amounts of vitamin D3 (cholecalciferol or calciol). The closely related vitamin D2 (ergocalciferol) arises from irradiation of the plant sterol ergosterol. This form of the vitamin has been widely used in fortification of milk. However, the natural vitamin D3 is more active in preventing rickets. The term vitamin Di was dropped when it was found to be a mixture of D2 and D3. The principal function of vitamin D is in the control of calcium metabolism. This control is exerted by polar, hydroxylated compounds of which the most important is la, 12-dihydroxy vitamin D3 (calcitriol). This hormone is distributed to all parts of the body. In cells of the intestinal lining it promotes uptake of calcium ions. It promotes reabsorption of both calcium and phosphate ions in the kidney tubules and increases blood calcium and depositon of calcium ions in bone. 

As with iron, zinc is an essential nutrient for normal growth and reproduction, and promotes wound healing and tissue repair. Zinc is a key component of many vital enzymes involved in most metabolic pathways. It is part of the enzyme retinene-reductase required for the proper functioning of vitamin A, and therefore indirectly affects vision. Zinc is also part of carbonic anhydrase, which is responsible for the transfer of carbon dioxide, especially in hanoglobin and renal tubules, and of car-boxypeptidase, key in protein metabolism. It also forms a complex with insulin, increasing the activity of this hormone, and helps to increase the activity of thymidine... 

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