Hypoxanthine-guanine phosphoribosyltransferase deficiency and erythrocyte synthesis of pyridine coenzymes.
Purine and pyridine metabolism were studied in ten Lesch-Nyhan patients, with virtually no hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity in erythrocytes. Increased NAD erythrocyte concentrations were found in all patients. Raised activities of two enzymes catalysing NAD synthesis from nicotinic acid (nicotinic acid phosphoribosyltransferase: NAPRT, and NAD synthetase: NADs) was found in erythrocyte lysates from all patients. The two enzymes had normal apparent Km for their substrates and increased Vmax. The rate of synthesis of pyridine nucleotides from nicotinic acid by intact erythrocytes in vitro was also increased in most patients. These findings suggest that raised NAD concentrations in HPRT- erythrocytes are due to enhanced synthesis as a result of increased enzyme activities.
Micheli
V
V
Dipartimento di Biologia Molecolare-Università di Siena, Italia. micheli@cuces.unisi.it
Sestini
S
S
Rocchigiani
M
M
Jacomelli
G
G
Manzoni
F
F
Peruzzi
L
L
Gathof
B S
BS
Zammarchi
E
E
Pompucci
G
G
D000293:Adolescent; D000328:Adult; D019732:Amide Synthases / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000201:enzymology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency*; D007223:Infant; D007700:Kinetics; D007926:Lesch-Nyhan Syndrome / Q000097:blood* / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009243:NAD / Q000096:biosynthesis* / Q000097:blood; D009539:Nicotinic Acids / Q000097:blood; D010430:Pentosyltransferases / Q000097:blood; D011685:Purine Nucleotides / Q000097:blood; D011687:Purines / Q000097:blood; D011725:Pyridines / Q000097:blood*; D011742:Pyrimidine Nucleotides / Q000097:blood; D014364:Tryptophan / Q000097:blood
D009539:Nicotinic Acids; D011685:Purine Nucleotides; D011687:Purines; D011725:Pyridines; D011742:Pyrimidine Nucleotides; D009243:NAD; D014364:Tryptophan; D010430:Pentosyltransferases; D007041:Hypoxanthine Phosphoribosyltransferase; D019732:Amide Synthases; C038479:NAD+ synthase; C021864:nicotinate phosphoribosyltransferase