Measurements were made of the activities of the enzymes of the 'de novo' and salvage pathways of purine synthesis [phosphoribosyl pyrophosphate amidotransferase (EC 2.4.2.14), adenine phosphoribosyltransferase (EC 2.4.2.7) and hypoxanthine phosphoribosyltranferase (EC 2.4.2.8)] at different stages of the lactation cycle, and the effects of diabetes on the activity of these enzymes in lactation were studied. A distinctive pattern of enzyme change was observed, in which the 'de novo' pathway enzyme phosphoribosyl pyrophosphate amidotransferase increased sharply between days 10 and 14 of pregnancy, and then remained sensibly constant until the height of lactation, whereas the enzymes of the salvage pathway increased later in pregnancy and continued to rise during lactation. Diabetes severely depressed the activity of the enzymes of the salvage pathway, but appeared to be without effect on the 'de novo' pathway enzyme. These results are discussed in relation to the provision of purine precursors from tissues outside the mammary gland.
Evidence for differences in the mechanism of renal growth in experimental diabetes
and compensatory hypertrophy after unilateral nephrectomy (UN) has been obtained
from measurements of the activity of enzymes of the de novo and salvage pathways of purine
synthesis in the kidneys of diabetic and UN rats and in doubly lesioned animals. In diabetes,
the activity of enzymes of both pathways increased. No effect of UN on the activity of any of
these enzymes was observed, nor was the effect of the double lesion greater than the effect of
diabetes alone. The activity of the pentose phosphate pathway increased in diabetes but not
as a result of UN. Again, the effect of the double lesion was no different from that of diabetes
alone. These results indicate that the accretion of nucleic acids in diabetes involves a larger
component of de novo synthesis, contrasting with UN, where depressed breakdown may play
a significant role.
Measurements were made of the activity of phosphoribosyl pyrophosphate amidotransferase (PPRibP-At, EC 2.4.2.14) and of adenine (APRT, EC 2.4.2.7) and hypoxanthine (HPRT, EC 2.4.2.8) phosphoribosyltransferases, representing the 'de novo' and salvage pathways respectively. PPRibP-At activity increased within 3 days of diabetes, whereas APRT and HPRT increased later. Incorporation of [14C]formate and of [8-14C]adenine into the nucleic acids of kidney slices showed that formate was incorporated earlier, and to a greater extent, than was adenine. These results indicate that, although the 'de novo' pathway for nucleotide synthesis is the main route in early diabetes, the salvage pathway assumes greater importance at later stages.
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