Vitamin metabolic degradation

Vitamins are vital (= vita) and mainly nitrogenous (= amines) substances of low-molecular weight. As a rule, they must be present in the diet as essential components. Only a few vitamins (e.g. A, K, Bi, B5, B12, folic acid, biotin) are formed in the intestine by bacteria. Plants constitute the main source of exogenous vitamin supply. In a biochemical context, the principal bio-catalytic effect of vitamins consists in substituting cofactors of enzymes which have undergone metabolic degradation. 

As discussed with other enzymes involved in vitamin A or D metabolism, there is interest in developing inhibitors of vitamin D degradation as opposed to administration of vitamin D itself, to raise levels of active vitamin D metabolites. Schuster [2445, 2488, 2489] has identified some inhibitors that differ in their selectivity between P450 24A1 and P450 27B1 and have sub-pM IC50 values. More inhibitors have been published in the... 

Enhanced biorestoration is a means by which naturally occurring processes are deliberately manipulated to increase or enhance the rate of cleanup. Biological activity in the subsurface is controlled by the availability of one or more of the necessary metabolic requirements such as an electron acceptor or nutrient. Although electron acceptors are most often the limiting factor, inadequate availability of nitrogen, phosphorus, or micronutrients (such as potassium, copper, or even vitamins) can restrict optimum restoration. When the proper balance of these factors is established, the rate of chemical degradation is maximized. 

The active form of vitamin Be, pyridoxai phosphate, is the most important coenzyme in the amino acid metabolism (see p. 106). Almost all conversion reactions involving amino acids require pyridoxal phosphate, including transaminations, decarboxylations, dehydrogenations, etc. Glycogen phosphory-lase, the enzyme for glycogen degradation, also contains pyridoxal phosphate as a cofactor. Vitamin Be deficiency is rare. 

As the principal thiolester of intermediary metabolism, acetyl coenzyme A is involved in two-carbon biosynthetic and degradative steps. An essential component is the vitamin pantithenic acid, which provides the sulfur atom for the thiolester formation. 

Not all agents can be readily metabolized. The toxic metals lead and mercury are elements that cannot be degraded but must still be removed from the body. Another important mechanism of detoxification is the attachment or binding of another compound to a toxic chemical to make it easier for the kidney to filter the compound out of the blood and excrete it in the urine. A primary purpose of the kidney is to screen the blood for waste products and concentrate them in the urine for excretion, as occurs, for example, with mercury. Caffeine is excreted in the urine at approximately the same concentration as the blood because the kidney cannot concentrate caffeine. Vitamins, however, are readily concentrated and excess quickly eliminated in the urine. 

Effects on growth and calorigenesis are accompanied by a pervasive influence on metabolism of drugs as well as carbohydrates, fats, proteins, and vitamins. Many of these changes are dependent upon or modified by activity of other hormones. Conversely, the secretion and degradation rates of virtually all other hormones, including catecholamines, cortisol, estrogens, testosterone, and insulin, are affected by thyroid status. 

Toluene, 3-chlorobenzoate, cinnamate, and 2-aminobenzoate can all be converted to benzoyl-CoA and be metabolized via the pathway of Eq. 25-9. Phenol, cresol, coumarate, protocatechuate, and vanillate can be converted to 4-hydroxybenzoyl-CoA and degraded in a similar fashion.166 The breakdown of various forms of vitamin B6 by bacteria is described in Section F (Eq. 25-24). 

Pyndoxal phosphate is also a cofactor for transamination reactions, In these reactions, an amino group is transferred from an amino acid to an or-keto acid, thus founing a new amino acid and a new or-keto acid, Transamination reactions are important for the synthesis of amino acids from non-protein metabolites and for the degradation of amino acids for energy production. Since pyridoxal phosphate is intimately involved ill amino add metabolism, the dietary requirement for vitamin B6 increases as the protein content of the diet increases. 

Identification of N-, P-, and S-containing compounds is difficult, and those that are identified tend to be metabolic products, such as nucleotides and vitamins, released into the soil following the death of cells. Broadly, nitrogen is an integral part of the humic molecule, and is released as NH4 ions when the humic material is degraded. Phosphorus and sulfur are more commonly found as P and S esters, which can be released as orthophosphate and sulfate ions by the action of phosphatase and sulfatase enzymes, respectively. 

There are many examples in the literature for applications of LC-NMR in the pharmaceutical industry. In the area of natural products, LC-NMR has been applied to screen plant constituents from crude extracts [54,57,67,68] and to analyze plant and marine alkaloids [69-72], flavonoids [73], sesquiterpene lactones [74,75], saponins [58,76], vitamin E homologues [77], and antifungal and bacterial constituents [56,78,79] as examples. In the field of drug metabolism, LC-NMR has been extensively applied for the identihcation of metabolites [42, 80-88] and even polar [89] or unstable metabolites [43]. And hnally, LC-NMR has been used for areas such degradation products [90-93], drug impurities [94-102], drug discovery [103,104], and food analysis [105-107]. 

Imines are particularly common as intermediates in many biological pathways, where they arc often called Schiff bases. The amino acid alanine, for instance, is metabolized in the body by reaction with the aldehyde pyridoxal phosphate (PLP), a derivative of vitamin Bg, to yield a Schiff base that is further degraded. 

It has been suggested that vitamin D3 (378) is metabolized into a more polar substance before stimulating calcium transport to the intestine. The principal metabolite from the blood, produced by the liver, has been found to be 25-hydroxycholecalciferol (379), whereas the trihydroxy-derivative (380) is the principal metabolite from the intestine. Autoxidation of cholesterol via hydroperoxide intermediates afforded a variety of hydroxylated cholesterol derivatives and products of side-chain degradation. ... 

Cd toxicity to kidneys can lead to degradation of vitamin D metabolism, which leads to osteoporosis Cd-induced nephotoxicity can also lead to decreased calcium and phosphate retention, which can produce osteomalacia (weakening of bones). 

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