Humans, deficiencies

Physiological functions as well as clinical symptoms that occur in humans deficient in specific vitamins are given in Table 6. It is becoming more authenticated that vitamins have additional potential health benefits when adrninistered, via the diet or by supplementation, at levels above those required for obviating deficiency. Although for most vitamins the optimal levels are not yet estabUshed, some of the potential health benefits to be derived from vitamins are indicated (16). In one case, the level of scientific proof is such that the U.S. FDA has allowed "a health cl aim that women who are capable of... 

Gonzalez FJ, Skoda RC, Kimura S, Umeno M, Zanger UM, Nebert DW et al. Characterization of the common genetic defect in humans deficient in debri-soquine metabolism. Nature 1988 331 442-446. 

Human deficiencies may occur when technologies, environments, and organizations are not appropriate for desired human performance. These discrepancies allow human performance deficiencies. 

Biotin (vitamin B ) is widespread in foods and is also synthesized by intestinal bacteria. It is a coenzyme for the carboxylation of pyruvate, acetyl-coenzyme-A (CoA), propionyl CoA, and /1-methyl-crotonyl CoA and is involved in fatty acid formation and in energy release from carbohydrates. In humans deficiencies only occur in patients with an abnormal gut flora and manifests itself as exfoliative dermatitis and alopecia. 

Vitamin B12 (cobalamin) serves as a cofactor for several essential biochemical reactions in humans. Deficiency of vitamin B12 leads to megaloblastic anemia (Table 33-2), gastrointestinal symptoms, and neurologic abnormalities. Although... 

Shetty B, Kosa M, Khalil DA, Webber S. Preclinical Pharmacokinetics and Distribution to Tissue of AG1343, an inhibitor of human deficiency virus type 1 protease. Antimicr. Ag. and Chemoth. 1996 40 110-114. 

Vitamin E deficiency is normally associated with diseases of fat malabsorption and is rare in humans. Deficiency is characterized by erythrocyte haemolysis and prolonged deficiency can cause neuromuscular dysfunction. Hypervitaminosis E is not common, despite an increased intake of vitamin E supplements. Extremely high doses of the vitamin may interfere with the blood clotting process. 

The nutritional status of an animal may affect the disposition of a foreign compound in vivo as well as the metabolism. Many drugs are protein-bound in the plasma, and alteration of the extent of binding for compounds extensively bound may have important toxicological implications. Thus, the decreased plasma levels of albumin after low-protein diets, such as occur in the human deficiency disease Kwashiorkor, might lead to significantly increased plasma levels of the free drug and therefore the possibility of increased toxicity. 

Essential ultratrace element in red algae, chick, rat, pig, goat, and probably humans. Deficiency results in depressed growth and increased mortality. 

For the most part, adequate copper is received in diet and widespread human deficiencies do not occur, but deficiencies may arise because of antagonists. The metals Cd, Hg, Ag and Zn interfere with copper metabolism, probably by competing for copper-binding sites in proteins. Ascorbic acid depresses intestinal absorption of copper56 (in contrast to iron). Some proteins in the diet adversely affect utilization of copper. The sulfide ion is a well known inhibitor of copper absorption, since it forms copper(II) sulfide which is insoluble.56... 

Miller AD, Jolly DJ, Friedmann T, Verma IM. 1983. A transmissible retrovirus expressing human hypoxanthine phosphoribosyltransferase (HPRT) Gene transfer into cells obtained from human deficient in HPRT. Proc Nat Acad Sci USA. 80 4709-4713. 

Epidemiological studies on human populations have suggested that humans deficient in vitamin A may bo at a greater risk for certain types of cancer. The converse situation, namely the treatment of cancer patients with vitamin A, has... 

The 1950s also saw the first evidence that chromium might be a dietary essential. Chromium is believed to promote the action of insulin and thus influences the metabolism of carbohydrates, fats, and proteins. Reports of severe human deficiency of chromium are rare and have been found primarily in people receiving only intravenous feedings for several months or years. Only a few laboratories in the world can accurately measure the amount of chromium in foods and body tissues because chromium is present in stainless steel, which is ubiquitous in analytical laboratories and easily contaminates biological samples. 

Correlating human medical conditions with the biochemical role of the tocopherols is difficult because of the lack of correlations between deficiency diseases seen in animals relative to what is seen in humans. Deficiency diseases seen in animals include reversible re-... 

Copper is a cofactor in several enzymes, including lysyl oxidase and superoxide dismutase. Ceruloplasmin, a deep-blue glycoprotein, is the principal copper-containing protein in blood. It is used to transport Cu2+ and maintain appropriate levels of Cu2+ in the body s tissues. Ceruloplasmin also catalyzes the oxidation of Fe2+ to Fe3+, an important reaction in iron metabolism. Because the metal is widely found in foods, copper deficiency is rare in humans. Deficiency symptoms include anemia, leukopenia (reduction in blood levels of white blood cells), bone defects, and weakened arterial walls. The body is partially protected from exposure to excessive copper (and several other metals) by metal-lothionein, a small, metal-binding protein that possesses a large proportion of cysteine residues. Certain metals (most notably zinc and cadmium) induce the synthesis of metallothionein in the intestine and liver. 

Cystathionine (made by cystathionine synthase from homocysteine and serine) plays a central role both in the biosynthesis of methionine in plants and bacteria and in the biosynthesis of cysteine in animals. In humans, deficiency of cystathionine synthase leads to a condition called homocystinuria, in which homocysteine overaccumulates. The condition results in severe mental retardation and dislocation of the lens of the eye. 

Human deficiency of erythrocyte pyruvate kinase leads to excessive blood levels of glycolytic intermediates and, importantly 2,3 bisphosphoglycerate. 

Apo C-II is a polypeptide of molecular weight 10,000 found primarily in VLDLs and, to a lesser extent, in chylomicrons (Table 18.1). Apo C-II activates Lipoprotein Lipase. A human deficiency of Apo C-II is associated with elevated triacylglycerol levels in blood. Apo E is also found in the Apo C-II gene cluster. 

Auchus, R.J. (2001). The genetics, pathophysiology, and management of human deficiencies of P450cl7. Endocrinol. Metah. Clin. North Am. 30,... 

Humans deficient in vitamin A lose their ability for dark adaptation. Rod vision is affected more than cone vision. Upon depletion of retinol from liver and blood, the concentrations of retinol and rhodopsin in the retina fall. Unless the deficiency is overcome, opsin, lacking the stabilizing effect of retinal, decays and anatomical deterioration of the rods outer segments occurs. In rats maintained on a vitamin A-deficient Set, irreversible ultrastructural changes leading to blindness then supervene, a process that takes -10 months. Following short-term deprivation of vitamin A, dark adaptation can be restored to normal by the addition of retinol to the Set, but this restoration takes several weeks. The reason for this delay is unknown. 

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