Biomedical subjects

S Santerini

Publications and source records attributed to S Santerini.

5 recordsLinked to original sources

PubMed1993

S-methyltransferases in human intestine: differential distribution of the microsomal thiol methyltransferase and cytosolic thiopurine methyltransferase along the human bowel.

1. The activities of the microsomal thiol methyltransferase and the cytosolic thiopurine methyltransferase were measured with 2-mercaptoethanol and 6-mercaptopurine as substrates in human ileum, ascending colon, transverse colon, descending colon and liver. 2. Thiol methyltransferase activity (pmol/min per mg) (mean +/- SD) was 495 +/- 280 (ileum), 786 +/- 454 (ascending colon), 1791 +/- 233 (transverse colon), 964 +/- 484 (descending colon) and 4800 +/- 1194 (liver). 3. Thiopurine methyltransferase (pmol/min per mg) (mean +/- SD) was 53.5 +/- 15.4 (ileum), 34.6 +/- 11.4 (ascending colon), 64.3 +/- 12.1 (transverse colon), 57.0 +/- 10.1 (descending colon) and 106 +/- 20.4 (liver). 4. Transferase in intestinal mucosa followed non-Michaelis-Menten kinetics, and two phases representing high and low affinity forms, for the acceptor methyl substrates were observed. 5. Comparison of intestinal with hepatic activities showed that thiopurine methyltransferase is better expressed than thiol methyltransferase in the human intestine, at least with the substrates studied.

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PubMed1991

Thiol methyltransferase in humans: development and tissue distribution.

Thiol methyltransferase (EC 2.1.1.9, TMT) activity was measured with 2-mercaptoethanol in the microsomal fraction of 12 placenta and 31 fetal and 33 adult liver specimens. TMT activity (nmol/min incubation/mg protein; mean +/- SD) was 0.61 +/- 0.25 (placenta), 0.74 +/- 0.45 (fetal liver), and 4.51 +/- 2.29 (adult liver). TMT activity was also measured in extrahepatic tissues and it was about one order of magnitude lower in fetal lungs, kidney and intestine as compared with the fetal liver. A similar distribution pattern was also observed in adult tissues except that in the kidney TMT activity was one third of the hepatic one. Studies of enzyme kinetics showed that fetal and adult hepatic TMT obeyed non-Michaelis-Menten kinetics when 2-mercaptoethanol was the varying substrate. Average values of Km for the higher and lower affinity phases were 0.03 and 14.05 mmol/l, respectively (fetal liver) and 0.005 and 14.57 mmol/l, respectively (adult liver). This paper shows that TMT develops prenatally and its distribution pattern is consistent with that of other microsomal enzymes, being preferentially associated with the liver both in the human fetus and in adult subject.

Adult↗

PubMed1991

Methylation of captopril in human liver, kidney and intestine.

1. The methylation of captopril was studied in the microsomal fraction from 20 human liver, 12 kidney, and 14 intestinal mucosa specimens. 2. The hepatic methyltransferase activity (mean +/- SD) was 477 +/- 204 pmol/min per mg. Renal and intestinal methyltransferase activities were 3 and 8 times lower, respectively, than hepatic activity. 3. The kinetics of methyltransferase with captopril as substrate were studied in four specimens of liver, kidney and intestine. The maximum velocities of reaction (mean +/- SD; pmol/min per mg) were 697 +/- 219 (liver), 456 +/- 120 (renal cortex), 264 +/- 77 (renal medulla) and 101 +/- 28 (ileum mucosa). Km values (mean +/- SD; mM) were 5.2 +/- 2.3 (liver) 4.3 +/- 1.7 (renal cortex) 4.1 +/- 1.5 (renal medulla) and 5.3 +/- 2.0 mM (ileum mucosa). Vmax is subjected to a marked tissue dependence whereas Km is similar in all tissues. 4. Liver is the primary site of captopril methylation whereas the intestine plays only a minor role. Kidney may contribute substantially to the hepatic methylation of captopril.

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PubMed1990

Conjugation pathways in liver disease.

1. The activities of microsomal glucuronyltransferase and thiomethyltransferase, and those of cytosolic sulphotransferase, acetyltransferase, glutathione transferase and thiomethyltransferase were measured in abnormal (cirrhosis and chronic hepatitis) and normal livers. 2. Glucuronyltransferase and sulphotransferase were investigated with 2-naphthol and ethinyloestradiol as substrates. p-Aminobenzoic acid, benzo(a)pyrene-4,5-epoxide and 2-mercaptoethanol were the substrates of acetyltransferase, glutathione transferase and thiomethyltransferase, respectively. 3. Enzyme activities are expressed as nmol min-1 incubation mg-1 protein and the averages (+/- s.d.) are given. With 2-naphthol as substrate, the glucuronyltransferase activity was 6.55 +/- 4.10 (abnormal liver, n = 33) and 7.81 +/- 4.02 (normal liver, n = 26) (NS); whereas sulphotransferase activity was 0.28 +/- 0.18 (abnormal liver, n = 35) and 0.68 +/- 0.43 (normal liver, n = 26) (P less than 0.01). Glucuronyltransferase activity towards ethinyloestradiol was 102.5 +/- 56.9 (abnormal liver, n = 30) and 107 +/- 59.9 (normal liver, n = 26) (NS), whereas sulphotransferase activity was 57.2 +/- 36.0 (abnormal liver, n = 35) and 122 +/- 67.6 (normal liver, n = 28) (P less than 0.01). Acetyltransferase activity was 0.84 +/- 0.83 (abnormal liver, n = 35) and 3.84 +/- 1.65 (normal liver, n = 26) (P less than 0.01). Glutathione transferase activity was 0.83 +/- 0.68 (abnormal liver, n = 35) and 2.90 +/- 1.59 (normal liver, n = 25) (P less than 0.01) and thiomethyltransferase activity was 1.00 +/- 0.69 (abnormal liver, n = 34) and 3.99 +/- 1.49 (normal liver, n = 25) (P less than 0.01). 4. Liver disease lowers the activities towards the substrates studied of sulphotransferase, acetyltransferase, glutathionetransferase and thiomethyltransferase but not that of glucuronyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Profile of drug-metabolizing enzymes in the cortex and medulla of the human kidney.

The cortex and medulla were isolated from kidneys whose donors (5 men and 1 woman, aged between 44 and 68 years) were undergoing nephrectomy to remove a tumor. Kidneys with normal architecture for at least two thirds of the organ were included in the study. Tissue specimens used in our experiments were free from pathological changes. The activities of the following enzymes of phase I NADPH cytochrome c reductase, aminopyrine N-demethylase, ethoxycoumarin O-deethylase, ethoxyresorufin O-deethylase, microsomal and cytosolic epoxide hydrolases, glutathione reductase and glutathione peroxidase, and those of the following enzymes of phase II glutathione transferase, glucuronyl transferase, sulphotransferase, acetyltransferase, thiomethyltransferase, thiopurinemethyltransferase, thioltransferase and glyoxalase were measured. The activity in renal cortex was significantly higher than in medulla for NADPH cytochrome c reductase, cytosolic epoxide hydrolase, glutathione reductase and glutathione peroxidase (phase I enzymes), and glutathione transferase, acetyltransferase, thiomethyltransferase, thiopurinemethyltransferase, thioltransferase and glyoxalase (phase II enzymes). The other enzymes had similar activity in cortex and medulla. The distribution pattern of drug-metabolizing enzymes in the human kidney cannot be considered as a single pattern because of the observed enzyme-dependent differences between cortex and medulla.

Adult↗