The effects of unilateral
nephrectomy (UN) and
streptozotocin (STZ) diabetes on the activities of
enzymes involved in
uridine and
cytidine synthesis in early renal growth (3-14 days after stimulus to growth) have been compared. Measurements were also made of
glucose-6-phosphate dehydrogenase (G6PDH) and
6-phosphogluconate dehydrogenase (6PGDH) and of
glucose 6-phosphate (G6P),
UDP-glucose, and
glycogen, in relation to
phosphoribosyl pyrophosphate,
ribonucleotide, and complex
carbohydrate formation. There were striking differences in the activities of
CTP synthetase, G6PDH, and 6PGDH in the two conditions, with a three-fold increase in all three
enzymes at 3 and 5 days and a two-fold increase above basal values at 14 days of STZ diabetes. The UN group showed no significant change in
CTP synthetase at any stage and the activity of G6PDH and 6PGDH only kept pace with renal growth. Changes in routes of
uridine synthesis were less marked, with a more rapid rise in
carbamoyl-phosphate synthetase (glutamine) and a lesser response of
dihydroorotate dehydrogenase in the UN relative to the STZ-diabetic groups. The
enzymes of complex II and of
uracil phosphoribosyltransferase showed essentially similar patterns during renal
hypertrophy in UN and STZ diabetes. The parallel increase in
CTP synthetase, G6PDH, and 6PGDH in the kidney in diabetes, also known to increase in growth situations in
hepatomas and in renal
tumors, is discussed in relation to
hormone signals involved in renal growth. The importance of the concentration of
CTP, and thus of
CTP synthetase, in the
CTP-cytidyltransferase reaction, an
enzyme with a high Km for
CTP, makes the present observation of the striking increase in
CTP synthetase in STZ diabetes of particular interest in relation to
phosphatidylcholine formation and
hormone signal transduction.