Enzymes of uracil catabolism in normal and neoplastic human tissues

Enzymes of the pyrimidine base catabolism, dihydrouracil dehydrogenase (EC 1.3.1.2), dihydropyrimidinase (EC 3.5.2.2), and beta-ureidopropionase (EC 3.5.1.6) were compared in the cytosolic extract of several normal and neoplastic human tissues. The activity was measured by following the catabolism o...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1985-11, Vol.45 (11), p.5405-5412
Main Authors: NAGUIB, F. N. M, EL KOUNI, M. H, SUNGMAN CHA
Format: Article
Language:English
Subjects:
Amidohydrolases - analysis
beta-Alanine - analogs & derivatives
beta-Alanine - metabolism
Biological and medical sciences
Dihydrouracil Dehydrogenase (NAD+)
Fluorouracil - metabolism
General aspects
Humans
Kinetics
Medical sciences
Neoplasms - enzymology
Oxidoreductases - analysis
Oxidoreductases - antagonists & inhibitors
Oxidoreductases Acting on CH-CH Group Donors
Tumors
Uracil - analogs & derivatives
Uracil - metabolism
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Enzymes of the pyrimidine base catabolism, dihydrouracil dehydrogenase (EC 1.3.1.2), dihydropyrimidinase (EC 3.5.2.2), and beta-ureidopropionase (EC 3.5.1.6) were compared in the cytosolic extract of several normal and neoplastic human tissues. The activity was measured by following the catabolism of [6-14C]-uracil to dihydrouracil, carbamyl-beta-alanine, and beta-alanine. Substrate inhibition, hysteresis, allosterism, and the lack of dihydropyrimidinase are pointed out as special problems in assaying enzymes of pyrimidine degradation. The activity of dihydrouracil dehydrogenase has been demonstrated in several human extrahepatic tissues and tumors. The enzyme is rate limiting in extrahepatic solid tumors but not in their normal counterparts. Some of these solid tumors contain greater amounts of activity than do their normal equivalents, which encourages the use of inhibitors of this enzyme in conjunction with treatment of these tumors by 5-fluorouracil. Because of the lack of a pattern in dihydrouracil dehydrogenase activity between tumors and normal tissues, the enzyme is not a good marker for tumorigenicity. Dihydropyrimidinase, on the other hand, is highly active in all solid tumors studied but not in their normal counterparts; therefore, we suggest that dihydropyrimidinase can serve as a good marker of tumorigenicity as well as a target for cancer chemotherapy of human solid tumors.
ISSN:0008-5472
1538-7445