Vitamin-like substances

Not all patients who present the same clinical picture respond to vitamin therapy. Thus, if the structural gene for an apoenzyme or transport molecule is completely absent because of a gene deletion, no amount of vitamin or cofactor will correct the defect. If the mutation affects substrate rather than cofactor binding, the pathway is blocked just as effectively and cannot be relieved by increased concentration of cofactor. Thus, six mutations have been identified that cause methylmalonic aciduria. 

About two dozen inherited diseases respond to pharmacological doses of a vitamin (Table 38-1). Many have been mentioned elsewhere in this book in conjunction with the affected metabolic pathways. Although most are very rare, their study has contributed much to acknowledge of metabolism in the human body. Some are heterogeneous in symptoms and in responsiveness to therapy, suggesting genetic heterogeneity, as discussed above. 

Several compounds, e.g., vitamin D and niacin, are apparently required in the diet even though pathways for their synthesis occur in the body. Such a situation may arise if a pathway does not provide an adequate supply for the body s needs or if the material cannot be readily transported from the site of synthesis to the place of action. The compounds discussed below are essential dietary nutrients in one or more nonhuman species, but such a status in humans is not supported by evidence. 

Choline (N,N,N-trimethyl-y6-hydroxyethylamine) is an important constituent of phospholipids (lecithin is phosphatidylcholine) and of acetylcholine. It can be completely synthesized from serine (Chapter 19), but only in the form of phosphatidylserine and then only when the dietary supply of amino acids is adequate. Betaine (N,N,N-trimethylglycine) readily replaces dietary choline for all species. Choline is conserved by a salvage pathway. In the lung, this salvage route is the principal route for the synthesis of the phosphatidylcholine needed as a surfactant (see Chapter 19). 

Inositol (hexahydroxycyclohexane) occurs in several isomeric forms. Myo-inositol (or meso-inositol) is an important constituent of phospholipids and is the only isomer with biological activity. Inositol hexaphosphate (phytic acid) is found in avian erythrocytes, where it binds to hemoglobin, thereby regulating the oxygen capacity of the blood. It is also important as an intracellular messenger in a number of pathways. 

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Beadle and Tatum had found that irradiation of Neurospora spores produced mutants which were incapable of carrying out certain well-defined chemical reactions, and it was at first supposed that as a result of the destruction of a specific gene, the potentiality for producing a particular enzyme was completely lost. The "wild type" of Neurospora could propagate satisfactorily when biotin was the only vitamin-like substance supplied in the culture medium. Of the many mutant strains produced, however, one needed, in addition to biotin, the vitamin riboflavin. Without a supply of riboflavin in the culture medium this so-called "riboflavinless mutant" would not grow. Since riboflavin is a part of an enzyme system always found in Neurospora, it is an obligatory cell constituent and either has to be produced by the cells themselves (as in the wild type) or supplied exogenously in... 

Certainly the possibility needs to be explored that nutritional supplements [and these may include not only substances known to be necessary for normal nutrition, but others as well (p. 184)] will prevent or cure the various types of mental disease. One cannot hope that a single nutrient factor, such as a vitamin, is going to be the answer for a multitude of people, even if their outward symptoms seem to be about the same. As each new vitamin or vitamin-like substance is discovered (and there are probably more to come), there is a great enthusiasm for its possibilities, oftentimes without regard for the fact that it is only one link in a chain and unless all links are present there is no chain. A single vitamin is likely to be a limiting factor in some process and not the only limiting factor. 

Vitamins are divided into two major categories. They are fat-soluble (A, D, E and K) and water-soluble vitamins (B-complex and vitamin C). B complex vitamins include thiamine (Bi), riboflavin (B2), pantothenic acid (B3), niacin (B5), pyridoxine (Be), biotin (By), folic acid (B9), and cobalamin (Biy). Inositol, cholic and para-aminobenzoic acid are vitamin-like substances sometimes classified as part of the B complex, but no convincing evidence has been shown so far to be included as vitamins. All the fat-soluble vitamins and some B vitamins exist in multiple forms. The active forms of vitamin A are retinol, retinal and retinoic acid and vitamin D is available as ergocalciferol (D2) and cholecalciferol (D3). The vitamin E family includes four tocopherols and four tocotrienols but a-tocopherol being the most abundant and active form. The multiple forms of vitamins are interconvertible and some are interchangeable. 

The B group vitamins and vitamin C serve as coenzymes or coenzyme precursors. The B complex includes thiamine, riboflavin, pyridoxine, niacin, pantothenic acid, biotin, folate, and cobalamin. Inositol, choline, and paraaminoben-zoic acid, usually classified as vitamin-like substances in humans, are sometimes included with the B-complex vitamins. They will be discussed briefly at the end of the chapter. The B vitamins occur in protein-rich foods... 

R6 Raskin, I. M. Vitamin-like substances. Orotic acid. Vitamins, 470, 81 (1974)... 

Vitamin-like Substances, and Microorganisms, Interrelations between Growth and Metabolism (Mdllv/ain). VII 409... 

Green Plants and Fungi, Antibacterial Substances from (Kavanagh) VII 461 Growth and Metabolism of Vitamin-like Substances, IrUerrelations... 

A. Further Examples of Metabolic Changes in Vitamin-like Substances 454... 

The present subject has been illustrated by changes in the two types of compound which have at present been most extensively studied. Changes in many ways comparable have been observed in several other vitamin-like substances. It is proposed to defer their detailed discussion, but the following brief account illustrates how general are the phenomena concerned, though in few cases have the metabolic changes been connected in any detail with characteristics of growth. 

Growth and Metabolism of Vitamin-like Substances, Interrelations... 

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