Vitamin Differentiation

Indirect indicators of vitamin B12 deficiency include measurements of the metabolites homocysteine and methylmalonic acid (MMA) in serum and MMA in urine (see the Biochemical Perspectives section). Whereas the serum homocysteine concentration increases during folate or vitamin B12 deficiencies, the serum and urine MMA concentrations increase only in vitamin B12 deficiency. Therefore, MMA determinations can be used to differentiate vitamin B12 deficiency from folate deficiency. The normal concentration of MMA in serum ranges from 0.08 to 0.28 pmol/L. MMA is quantified using gas-liquid chromatography and mass spectrometry. Elevated concentrations of MMA and homocysteine in serum may precede the development of hematological abnormalities and reductions in serum vitamin B12 concentrations. One should be aware that other conditions, including renal in sufficiency and inborn errors of metabolism, can also result in elevated serum levels of MMA. 

The fat-soluble vitamins are lipids that are involved in such varied functions as vision, growth, and differentiation (vitamin A), blood clotting (vitamin K), prevention of oxidative damage to cells (vitamin E), and calcium metabolism (vitamin D). 

B. Other useful laboratory studies include CBC with manual differential, vitamin... 

In its second role, in the regulation of cellular differentiation, vitamin A is involved in the formation and protection of epithelial tissues and mucous membranes. In this way it has particular importance in growth, reproduction and immune response. Vitamin A is important in the resistance to disease and promotion of healing through its effect on the immune system and epithelial integrity. In addition, it acts, along with vitamins E and C and 3-carotene, as a scavenger of free radicals (see Box 5.2, p. 83). 

RP columns having a high carbon loading [107—109] can differentiate vitamin D2 from D3, making possible the use of one homolog as an internal standard for the other [107] as well as facilitating the separation of their hydroxylated metabolites [108]. 

Many plant substances possess antivitamin D activity but the mode of action and in most cases the identity remain unknown. Rachitogenic factors have been observed in yeast. Because of the metaboHc interrelationships that exist between vitamin D, Ca, and P, it is sometimes difficult to differentiate between chelators of mineral elements and tme antivitamins. One reported vitamin D antagonist in oats was later identified as phytic acid (72). 

Dihydroxyvitamin (283) is the endogenous ligand for the vitamin receptor (VDR). It modulates genomic function in a tissue and developmentaHy specific manner and affects ceU proliferation, differentiation, and mineral homeostasis (74). Vitamin mobilizes calcium from the bone to maintain plasma Ca " levels. Vitamin and VDR are present in the CNS where they may play a role in regulating Ca " homeostasis. Vitamin D has potent immunomodulatory activity in vivo. 

Fohc acid is a precursor of several important enzyme cofactors required for the synthesis of nucleic acids (qv) and the metaboHsm of certain amino acids. Fohc acid deficiency results in an inabiUty to produce deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and certain proteins (qv). Megaloblastic anemia is a common symptom of folate deficiency owing to rapid red blood cell turnover and the high metaboHc requirement of hematopoietic tissue. One of the clinical signs of acute folate deficiency includes a red and painhil tongue. Vitamin B 2 folate share a common metaboHc pathway, the methionine synthase reaction. Therefore a differential diagnosis is required to measure foHc acid deficiency because both foHc acid and vitamin B 2 deficiency cause... 

The specific role of vitamin A in tissue differentiation has been an active area of research. The current thinking, developed in 1979, involves initial dehvery of retinol by holo-B >V (retinol-binding protein) to the cell cytosol (66). Retinol is then ultimately oxidized to retinoic acid and binds to a specific cellular retinoid-binding protein and is transported to the nucleus. Retinoic acid is then transferred to a nuclear retinoic acid receptor (RAR), which enhances the expression of a specific region of the genome. Transcription occurs and new proteins appear during the retinoic acid-induced differentiation of cells (56). 

In the treatment of diseases where the metaboUtes are not being deUvered to the system, synthetic metaboUtes or active analogues have been successfully adrninistered. Vitamin metaboUtes have been successfully used for treatment of milk fever ia catde, turkey leg weakness, plaque psoriasis, and osteoporosis and renal osteodystrophy ia humans. Many of these clinical studies are outlined ia References 6, 16, 40, 51, and 141. The vitamin D receptor complex is a member of the gene superfamily of transcriptional activators, and 1,25 dihydroxy vitamin D is thus supportive of selective cell differentiation. In addition to mineral homeostasis mediated ia the iatestiae, kidney, and bone, the metaboUte acts on the immune system, P-ceUs of the pancreas (iasulin secretion), cerebellum, and hypothalamus. 

A process has been disclosed in which the mixture of naphthoquinones is reacted with a diene such as butadiene. Owing to the fact that the undesked product is an unsubstituted naphthoquinone, this dieneophile readily reacts to form a Diels-Alder adduct. By appropriate control of reaction parameters, Htde reaction is observed with the substituted naphthoquinone. Differential solubiUty of the adduct and vitamin allows for a facile separation (57,58). 

Retinoids are needed for cellular differentiation and skin growth. Some retinoids even exert a prophylactic effect on preneoplastic and malignant skin lesions. Fenretlnide (54) is somewhat more selective and less toxic than retinyl acetate (vitamin A acetate) for this purpose. It is synthesized by reaction of all trans-retinoic acid (53), via its acid chloride, with g-aminophe-nol to give ester 54 (13). 

Vitamin A (retinol) and its naturally occurring and synthetic derivatives, collectively referred to as retinoids (chemical structure), exert a wide variety of profound effects in apoptosis, embryogenesis, reproduction, vision, and regulation of inflammation, growth, and differentiation of normal and neoplastic cells in vertebrates. 

Summary term for a number of steroid hormones and their precursors with differentiation-inducing activity in many tissues. As regards bone, three components are relevant cholecalciferol ( vitamin D ) 25-hydroxyvi-taminD3 (calcidiol) and 1,25-dihydroxy vitamin D3 (calcitriol). The latter is the biologically active form and increases both intestinal calcium absoiption and bone resorption. Vitamin D preparations are widely used for the treatment of osteoporosis. Daily supplementation with vitamin D reduces bone loss in postmenopausal women and hip fractures in elderly subjects. 

A most important function of vitamin A is in the control of cell differentiation and mrnover. PsA-trans-retinoic acid and 9-cw-retinoic acid (Figure 45-1) regulate growth, development, and tissue differentiation they have different actions in different tissues. Like the steroid hormones and vitamin D, retinoic acid binds to nuclear receptors that bind to response elements of DNA and regulate the transcription of specific genes. There are two families of nuclear retinoid receptors the retinoic acid receptors (RARs) bind all-rrijw-retinoic acid or 9-c -retinoic acid, and the retinoid X receptors (RXRs) bind 9-cw-retinoic acid. 

Vitamin A is essential throughout life, including foetal development, but perhaps its most well researched role is that in vision where 11 -cis retinaldehyde is the initial part of the photoreceptor complex in rods and cones. Retinoic acid induces differentiation in epithelial cells and deficiency leads to... 

Vitamin A (retinol) and retinoic acid are carotenoid oxidation compounds that are very important for human health. The main functions of retinoids relate to vision and cellular differentiation. With the exception of retinoids, it was only about 10 years ago that other carotenoid oxidation products were first thought to possibly exert biological effects in humans and were implicated in the prevention - or promotion of degenerative diseases. A review on this subject was recently published. ... 

Vitamin D analogues (calcipotriol, calcitriol, and tacalcitol) are also frequently selected as initial pharmacotherapy in the management of mild to moderate psoriasis.2 These inhibit keratinocyte differentiation and proliferation and maybe antiinflammatory.2 Unlike corticosteroids, tachyphylaxis does not occur with prolonged use. Clearance of lesions should occur after 4 to 6 weeks of treatment.2 Lack of response by 8 weeks... 

Reboul, E, Thap, S, Toumiaire, F, Andre, M, Juhel, C, Morange, S, Amiot, MJ, Lairon, D, and Borel, P, 2007b. Differential effect of dietary antioxidant classes (carotenoids, polyphenols, vitamins C and E) on lutein absorption. Br J Nutr 97, 440-446. 

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