The postnatal development of brain metabolism.

acyl-CoA synthetase and carnitine acyltransferase I not only exhibit the greatest adaptive responses during development but also show the most dramatic increases in activity in the livers of adult rats subjected to experimental conditions known to result in an increase in hepatic fatty acid degradation (P. A. Chalk & E. Bailey, unpublished work). It seems possible that these enzymes may fulfil a rate-limiting role in fatty acid oxidation. It was therefore of interest to study detailed changes in the activities of these enzymes immediately after birth and the effect of the nature of the diet consumed on such activities. The results presented in Table 1, when considered in conjunction with previous work (Foster & Bailey, 1976a; Higham et al., 1980), indicate that whereas the perinatal increase in palmitoyl-CoA synthetase is probably not related to the intake of the high-fat diet of suckling, the increase in carnitine palmitoyltransferase I is. Thus the increase in palmitoyl-CoA synthetase activity occurs very rapidly in the fostered animals, but does not occur at all in the fat-fed animals, which show a similar response to the carbohydrate-fed and starved animals. The rapidity of the change in the fostered animals suggests an activation process rather than enzyme synthesis, and, since these animals may have a period of cold exposure compared with the other experimental groups maintained in a Humidicrib, it is possible that hormonal changes caused by the cold exposure may influence the activity of the palmitoyl-CoA synthetase. No change in carnitine palmitoyltransferase I or I1 activities occurs during the experimental period studied, although a large increase in the activity of carnitine palmitoyltransferase I occurs after 18 h of extrauterine life, i.e. subsequent to considerable amounts of milk intake (Foster & Bailey, 1976a; Higham et al., 1980) Since McGarry et al. ( I 977) have demonstrated that malonyl-CoA inhibits carnitine palmitoyltransferase I, it might be argued that in vivo the activity of this enzyme does indeed rise immediately after birth as lipogenesis and hence malonyl-CoA concentrations fall. However, as discussed by Pillay & Bailey ( l98l) , a considerable fall in hepatic lipogenesis appears to occur before birth. The results in Table 1 also indicate that in the fat-fed animals blood ketones, and presumably hepatic fatty acid degradation, increase without an increase in acyl CoA synthetase much above the value in the newborn. It seems possible that the increase in the acyl-CoA synthetase in fostered animals is not necessary for the relatively low rates of fatty acid degradation occurring, and that it occurs in anticipation of the large increase in fatty acid oxidation and ketogenesis which takes place after 12-18h of life and which also requires the induction of carnitine acyltransferase I and hydroxymethylglutaryl-CoA synthase (Higham et al., 1980).