Risks tissue metabolic activity, factors

The brain has a number of characteristics that make it especially susceptible to free- radical-mediated injury. Brain lipids are highly enriched in polyunsaturated fatty acids and many regions of the brain, for example, the substantia nigra and the striatum, have high concentrations of iron. Both these factors increase the susceptibility of brain cell membranes to lipid peroxidation. Because the brain is critically dependent on aerobic metabolism, mitochondrial respiratory activity is higher than in many other tissues, increasing the risk of free radical Teak from mitochondria conversely, free radical damage to mitochondria in brain may be tolerated relatively poorly because of this dependence on aerobic metabolism. 

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). 

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