Vitamin metabolic pathways

The use of foods by organisms is termed nutrition. The ability of an organism to use a particular food material depends upon its chemical composition and upon the metabolic pathways available to the organism. In addition to essential fiber, food includes the macronutrients—protein, carbohydrate, and lipid—and the micronutrients—including vitamins and minerals. 

Metabolic diseases, liquid crystal accumulations and, 15 112-113 Metabolic engineering, 12 412-413 Metabolic functions, of vitamin A, 25 787-789 Metabolic pathways, as target of antibiotics, 3 24... 

The metabolism of cyanide has been studied in animals. The proposed metabolic pathways shown in Figure 2-3 are (1) the major pathway, conversion to thiocyanate by either rhodanese or 3-mercapto-pyruvate sulfur transferase (2) conversion to 2-aminothiazoline-4-carboxylic acid (Wood and Cooley 1956) (3) incorporation into a 1-carbon metabolic pool (Boxer and Richards 1952) or (4) combining with hydroxocobalamin to form cyanocobalamin (vitamin B12) (Ansell and Lewis 1970). Thiocyanate has been shown to account for 60-80% of an administered cyanide dose (Blakley and Coop 1949 Wood and Cooley 1956) while 2-aminothiazoline-4-carboxylic acid accounts for about 15% of the dose (Wood and Cooley 1956). The conversion of cyanide to thiocyanate was first demonstrated in 1894. Conversion of cyanide to thiocyanate is enhanced when cyanide poisoning is treated by intravenous administration of a sulfur donor (Smith 1996 Way 1984). The sulfur donor must have a sulfane sulfur, a sulfur bonded to another sulfur (e.g., sodium thiosulfate). During conversion by rhodanese, a sulfur atom is transferred from the donor to the enzyme, forming a persulfide intermediate. The persulfide sulfur is then transferred... 

Riboflavin (vitamin B2) is a component of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), coenzymes that play a major role in oxidation-reduction reactions (see Section 15.1.1). Many key enzymes involved in metabolic pathways are actually covalently bound to riboflavin, and are thus termed flavoproteins. 

Fluorination of the vitamin D3 side chain was anticipated to have an impact on its metabolism pathway. 26,27-Hexafluorocalcitriol, faiecaicitrioi, was found to be several times more potent than caicitrioi in the regulation of Ca metabolism and of the immune system. The reason for this higher biological activity has been attributed to several mechanisms a higher activity of its 23(5)-hydroxylated metabolite [26,27-hexafluoro-l,23(5),25(OH)3D3], a lower affinity of faiecaicitrioi for the vitamin D binding protein and a higher affinity of falecalcitriol-... 

Riboflavin (vitamin B2 6.18) consists of an isoalloxazine ring linked to an alcohol derived from ribose. The ribose side chain of riboflavin can be modified by the formation of a phosphoester (forming flavin mononucleotide, FMN, 6.19). FMN can be joined to adenine monophosphate to form flavin adenine dinucleotide (FAD, 6.20). FMN and FAD act as co-enzymes by accepting or donating two hydrogen atoms and thus are involved in redox reactions. Flavoprotein enzymes are involved in many metabolic pathways. Riboflavin is a yellow-green fluorescent compound and, in addition to its role as a vitamin, it is responsible for the colour of milk serum (Chapter 11). 

Deficiency of vitamins, such as folic acid, is highly teratogenic, as essential synthetic metabolic pathways are blocked or reduced. This may be caused by the administration of specific vitamin analogues or antagonists as well as by a failure in supply. 

Inhibitors are substances that tend to decrease the rate of an enzyme-catalysed reaction. Although some act on the substrate, the discussion here will be restricted to those inhibitors which combine directly with the enzyme. Inhibitors have many uses, not only in the determination of the characteristics of enzymes, but also in aiding research into metabolic pathways where an inhibited enzyme will allow metabolites to build up so that they are present in detectable levels. Another important use is in the control of infection where drugs such as sulphanilamides competitively inhibit the synthesis of tetrahydrofolates which are vitamins essential to the growth of some bacteria. Many antibiotics are inhibitors of bacterial protein synthesis (e.g. tetracyclin) and cell-wall synthesis (e.g. penicillin). 

The many diverse components of milk have demonstrable effects on human health. Perhaps, the most commonly associated component of dairy food is that of dietary calcium. Dairy products provide the most significant contribution to dietary calcium intake in the modem Western diet. It has been estimated that dairy products contribute to >72% of dietary calcium in the United States (Huth et al., 2006). Calcium is an important mineral for maintenance of optimal bone health (Bonjour et al., 2009) and is an integral component of key metabolic pathways relating to, for example, muscle contraction both in skeletal and smooth muscle (Cheng and Lederer, 2008). Further, dairy products contribute other essential nutrients in the diet, such as proteins, phosphorus, potassium, zinc, magnesium, selenium, folate, riboflavin, vitamin B12, and vitamin A (Haug et al., 2007 Huth et al., 2006). Low-fat milk alternatives are fortified with vitamin A and vitamin D which is added to milk and fermented milk in many countries making it an important source for vitamin D (Huth et al., 2006). 

Scheme V. Metabolic pathway for vitamin D. From J. Pharm. Sci. 71, 137 (1982). Reproduced with permission of the copy-right owner.

Biochemistry is important in many fields of science in addition to medicine. For instance, biochemists investigate food by studying molecules such as vitamins, amino acids, fatty acids, various minerals, and water, all of which are dietary requirements for healthy nutrition. They also explain how these nutrients are absorbed by the body and what they do in the cells. For example, the question of how the body derives energy from dietary fats and oils involves a series of biochemical reactions explained by the biochemistry of the metabolic pathways. 

As shown in the review of the homocysteine metabolism, vitamin B 2, vitamin B6, and folate are important cofactors in the metabolic pathways for homocysteine elimination, and consequently, deficiencies of these vitamins are characterized by elevated plasma concentrations of tHcy. Hyperhomocysteinemia is also frequently found in diseases such as renal failure, rheumatic and auto-immune diseases, hypothyroidism, and malignancies. Several drugs are also known to increase plasma tHcy concentrations (16-24). 

Although measurement of the concentration of vitamin B12 in serum is the most widely used test for the investigation of a possible deficiency, there are a number of other tests used to measure absorption, the integrity of the methylmalonyl metabolic pathway, and the presence of antibodies to intrinsic factor. These additional tests are also described in this section. 

Vitamin D deficiency remains the most common cause of rickets and osteomalacia in the world, with the exception of the United States and the Scandinavian countries where most dairy products are supplemented with this vitamin. This deficiency can be caused either by dietary habits or by insufficient exposure to ultraviolet light. The same type of symptoms can be observed when there is interruption of the normal vitamin D metabolic pathways due to a number of liver and/or kidney diseases. In addition, a number of inherited factors can lead to different types of vitamin D resistance which require massive supplements of vitamin D and/or minerals. Extensive reviews have been published depicting both the clinical features and their most likely causes, as well as the possible treatments of the different types of clinical disorders resulting from vitamin D deficiencies [113-117], The newly defined role for l,25(OH)2D3 upon the hematopoietic system could also have clinical relevance in bone disorders such as osteoporosis where patients have been shown to possess abnormal T-cell subsets [118]. 

Measurement of blood tHcy is usually performed for one of three reasons (1) to screen for inborn errors of methionine metabolism (2) as an adjunctive test for cobalamin deficiency (3) to aid in the prediction of cardiovascular risk. Hyperhomocysteinemia, defined as an elevated level of tHcy in blood, can be caused by dietary factors such as a deficiency of B vitamins, genetic abnormalities of enzymes involved in homocysteine metabolism, or kidney disease. All of the major metabolic pathways involved in homocysteine metabolism (the methionine cycle, the transsulfuration pathway, and the folate cycle) are active in the kidney. It is not known, however, whether elevation of plasma tHcy in patients with kidney disease is caused by decreased elimination of homocysteine in the kidneys or by an effect of kidney disease on homocysteine metabolism in other tissues. Additional factors that also influence plasma levels of tHcy include diabetes, age, sex, lifestyle, and thyroid disease (Table 21-1). 

Metabolic pathway engineering [125] is used to optimise the production of the required product based on the amount of substrate (usually biomass-derived) consumed. A so-called biobased economy is envisaged in which commodity chemicals (including biofuels), specialty chemicals such as vitamins, flavors and fragrances and industrial monomers will be produced in biorefineries (see Chapter 8 for a more detailed discussion). 

Insects have an unusual pathway for catabolizing propionate which may be related to the absence or low levels of vitamin found in many species. The propionate to acetate pathway is present in all insects which have been studied, including the termite, which has high levels of vitamin B1 . The presence of this unusual metabolic pathway for propionate metabolism offered the potential for selectivity in developing insect control... 

Abnormal accumulation in tissues and overloading of normal metabolic pathways, leading to signs of toxicity and possibly irreversible lesions. Niacin (Section 8.7.1), and vitamins A (Section 2.5.1), D (Section 3.6.1), and Bg (Section 9.6.4) are all known to be toxic in excess (see Section 1.2.4.3 for a discussion of tolerable upper levels of intake). 

The reaction catalyzed by delta-6-desaturase enzyme is the slowest reaction in the metabolic pathway of LA and is considered as a rate-limiting step (4, 5). Activity of this enzyme further decreases with age and in people suffering from various diseases, including arthritis, diabetes, hypertension, eczema, psoriasis, and so on. Lifestyle factors like stress, smoking, excessive consumption of alcohol, linoleic acid (6), saturated and trans-fatty acids and nutritional deficiencies of Vitamin B6, zinc (7), and magnesium inhibit this desaturase. As a result of limitations in in vivo production of GLA, supplementation with preformed GLA is becoming important. This has led to interest in development and commercialization of the sources of GLA. 

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