Uridine and cytidine nucleotide synthesis in renal hypertrophy: biochemical differences in response to the growth stimulus of diabetes and unilateral nephrectomy.
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.
Kunjara
S
S
Department of Biochemistry, University College and Middlesex School of Medicine, London, Great Britain.
Sochor
M
M
Ali
M
M
Bennett
M
M
Greenbaum
A L
AL
McLean
P
P
D000818:Animals; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000378:metabolism; D019731:Carbon-Nitrogen Ligases; D003597:Cytosine Nucleotides / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D000090722:Dihydroorotate Dehydrogenase; D006984:Hypertrophy; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008025:Ligases / Q000378:metabolism; D008297:Male; D009392:Nephrectomy; D009962:Orotate Phosphoribosyltransferase / Q000378:metabolism; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors; D010430:Pentosyltransferases / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014500:Uracil Nucleotides / Q000378:metabolism*
D003597:Cytosine Nucleotides; D000090722:Dihydroorotate Dehydrogenase; D014500:Uracil Nucleotides; D012313:RNA; D004247:DNA; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; D010430:Pentosyltransferases; D009962:Orotate Phosphoribosyltransferase; C023269:uracil phosphoribosyltransferase; D009964:Orotidine-5'-Phosphate Decarboxylase; D008025:Ligases; D019731:Carbon-Nitrogen Ligases; C019951:CTP synthetase; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)