Measurements have been made of the activity of the enzymes of the glycolytic, pentose phosphate and lipogenic pathways and of some marker enzymes of the tricarboxylic acid cycle in brains of rats aged between 20 days and 24 months. In general, the activity of the most enzymes measured was unchanged by aging but exceptions to this were increases of hexokinase, glucose-6-phosphate dehydrogenase and ‘malic enzyme’ and decreases of ATPcitrate lyase, acetyl-CoA carboxylase and fatty acid synthetase. An exceptionally large (2-fold) increase in the activity of cytosolic glycerol 3-phosphate dehydrogenase was noted. These changes are considered in relation to the overall metabolic activity of the brain.

Measurements have been made of the enzymes of glutathione metabolism and of NADPH generation in the brains of rats aged between 1 day and 24 months. The activity of glutathione peroxidase fell while that of glutathione reductase rose during the aging process. The four NADPH-generating systems each showed a different profile with respect to aging, the most marked changes occurring between 1 day and 20 days. Subsequently, the systems remained close to, or above, the young adult value. The role of the glutathione-metabolising enzymes in controlling the H(2)0(2) metabolism and suppressing peroxidative damage to the brain is discussed.

The flux of glucose in the pathways of acetyl group formation and disposal and the activities of a range of enzymes related to these processes have been measured in the brains of rats aged between 1 day and 24 months. The pattern of enzyme change is such that those systems involved in hydrogen transfer appear to increase disproportionately, relative to the glycolytic flux in the aged brain. It is suggested that these increases are an essential corollary to the need for a maintained glycolytic flux in a tissue dependent upon glucose as a fuel and one in which alternative routes of NADH oxidation diminish with age.