Vitamin B6 metabolism

Metabolism of Cofactors, Vitamins, and Other Substances Thiamin metabolism Riboflavin metabolism Vitamin B6 metabolism Nicotinate and nicotinamide metabolism... 

Tryfiates GP. Vitamin B6 metabolism and role in growth. Westport, CT Food and Nutrition Press, Inc, 1980. 

Narisawa S, Wennberg C, Millan JL (2001) Abnormal vitamin B6 metabolism in alkaline phosphatase knock-out mice causes multiple abnormalities, but not the impaired bone mineralization. J Pathol 193 125-133... 

In experimental animals, however, chronic dosing with isoniazid causes degeneration of the peripheral nerves. The biochemical basis for this involves interference with vitamin B6 metabolism. Isoniazid... 

Hydralazine (Apresoline) Directly relaxes arterioles (not veins) independent of sympathetic interactions. Causes decrease in blood pressure leading to reflex tachycardia and increased cardiac output. Directly increases renal blood flow. Moderate hypertension. May be used in pregnant women who are hypertensive. Reflex tachycardia, palpitations, fluid retention, systemic lupus erythematosis-liKe syndrome. Chronic therapy may lead to peripheral neuritis (due to interference with vitamin B6 metabolism in neural tissue). 

FIG. 1. Proposed major pathway of vitamin B6 metabolism. PN, pyridoxine PNP, pyridoxine S -phosphate PM, pyridoxamine PMP, pyridoxamine S -jdiosphate PL, pyridoxal PLP, pyridoxal S -phosphate PA, 4-pyridoxic add. 

Modeling vitamin B6 metabolism is further complicated by the fact that the activity of the kinase, oxidase, and phosphatase enzymes varies between organs and species. A very simplified diagram of vitamin B6 metabolism is shown in Fig. 2. In the intestine any phosphoiylated forms are hydrolyzed. The free vitamers are readily taken up by diffusion into the intestinal wall where significant phosphorylation (Middleton, 1979) and other metabolism (Middleton, 1985) occurs. In mice small doses (up to 14 nmol) of pyridoxine (Sakurai et aL, 1988) and pyridoxamine (Sakurai et oL, 1992) were converted almost completely to pyridoxal before being released into the portal circulation. While it is dear that the intestinal microflora produce vitamin B6,... 

The role of erythrocytes in vitamin B6 metabolism remains uncertain. Mouse and human erythrot es have higher oxidase activity and, therefore, convert pyridoxine to pyridoxal phosphate appreciably faster than erythrocytes from rat, hamster, and rabbit (Fonda, 1988). Anemic rats showed increased urinary loss of label administered as pyridoxal, suggesting that uptake by erythrocytes may conserve pyridoxal (Ink and Henderson, 1984). 

Pregnancy and lactation pose some difficult challenges for modeling vitamin B6 metabolism. Pyridoxal phosphate concentrations in plasma decline during pregnancy. Much of this decline appears to be correlated with the increased activity of placental alkaline phosphatase. Barnard et al. (1987) found that pyridoxal concentrations in pregnant women increased to compensate for the decline in pyridoxal phosphate. 

Our interest in vitamin B6 was stimulated by reports that vitamin B6 metabolism was altered in Down s syndrome (McCoy et al., 1%9). Since Down s syndrome is associated with trisomy of chromosome 21, it seemed most likely that we would be dealing with altered rates of metabolism. Therefore, we have been attempting to examine the kinetic aspects of vitamin B6 metabolism. 

There have been three basic approaches to examining the kinetics of vitamin B6 metabolism. One has been to examine individual enzymes (Merrill and Henderson, 1990) or tissues (Middleton, 1985 Mehansho and Henderson, 1980 Mehansho et aL, 1979,1980 Hamm et al, 1979,1980 Buss et al, 1980). A second has been to examine the changes with time after administration of unlabeled (Ubbink et al, 1987 Hamaker et al, 1990 ... 

The above discussion clearly illustrates the importance of muscle in vitamin B6 metabolism under altered nutrient intake. What would happen to vitamin B6 metabolism if musde metabolism were altered without altering vitamin B6 intake. Such circumstances exist in a microgravity environment or under conditions of prolonged bed rest. Muscle mass decreases even though nutrient intake is adequate. We had an opportunity to measure... 

Models of vitamin B6 metabolism should allow for differences between oral and intravenous administration of label. 

The conservation and flushing effects observed in vitamin B6 metabolism can be simulated by binding relationships. 

Our interest in McArdle s disease and vitamin B6 metabolism is stimulated by consideration of the consequences of the loss of the major, slowly metabolizing pool of vitamin B6 in the body. It is conceivable that the whole body phosphorylase-derived pool acts as a buffer to compensate for day-to-day variation in vitamin B6 intake. It will therefore be important to assess the rate of degradation of phosphorylase in the human, and the stable isotope method we have developed is directly applicable to this problem. Analysis of the same kinetics in McArdle s patients will define the role of muscle phosphorylase in the compartmen-talization of vitamin B6. 

It is conceivable that McArdle s patients need to pay greater attention to their vitamin B6 status than normal individuals. A compromised vitamin B6 status might be of even greater significance if McArdle s patients are more reliant on amino acid metabolism for muscle work—transaminases are PLP-dependent enzymes. Preliminary studies in our laboratory have established that McArdle s patients show differences in vitamin B6 metabolism and that they respond quickly and dramatically to short-term changes in vitamin B6 status (Beynon etal, 1995). Whether improvement of vitamin B6 status could enhance muscle performance remains to be seen. 

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