scholarly journals Formation of acetoacetate from 3-hydroxy-3-methylglutarate by rat liver and isolation of a mitochondrial coenzyme A-transferase activity involved

1974 ◽  
Vol 138 (3) ◽  
pp. 481-486 ◽  
Author(s):  
R. Deana ◽  
R. Meneghello ◽  
L. Manzi ◽  
C. Gregolin
Keyword(s):  
Rat Liver ◽  
Coenzyme A ◽  
Mitochondrial Fraction ◽  
Transferase Activity ◽  
Perfused Rat Liver ◽  
Km Value

1. Formation of acetoacetate from 3-hydroxy-3-methylglutarate was observed in the perfused rat liver. Production of 3.5μmol of acetoacetate/h per g of tissue was obtained. 2. Formation of acetoacetate was catalysed mainly by the mitochondrial fraction of the homogenized liver, at a rate of 62nmol/h per mg of protein. 3. Experiments with hydroxy-[3-14C]methylglutarate demonstrated that the acetoacetate formed was derived mainly from this compound. 4. A mitochondrial transferase activity catalysing the transfer of a CoA molecule from succinyl-CoA (3-carboxypropionyl-CoA) to hydroxymethylglutarate was shown. The Km value for hydroxymethylglutarate was 5×10−3m.

Uptake and distribution of exogenous CoQ in the mitochondrial fraction of perfused rat liver

1994 ◽  
Vol 15 ◽  
pp. s47-s55 ◽  
Author(s):  
M.L. Genova ◽  
C. Bovina ◽  
G. Formiggini ◽  
V. Ottani ◽  
S. Sassi ◽  
...  
Keyword(s):  
Rat Liver ◽  
Mitochondrial Fraction ◽  
Perfused Rat Liver

scholarly journals Comparative studies on the 25-hydroxylations of cholecalciferol and 1α-hydroxycholecalciferol in perfused rat liver

1978 ◽  
Vol 170 (3) ◽  
pp. 495-502 ◽  
Author(s):  
Masafumi Fukushima ◽  
Yasuho Nishii ◽  
Michiko Suzuki ◽  
Tatsuo Suda
Keyword(s):  
Vitamin D ◽  
Rat Liver ◽  
Linear Relation ◽  
Comparative Studies ◽  
Similar Rate ◽  
The Other ◽  
Perfused Rat Liver ◽  
Km Value ◽  
Derivatives Of ◽  
25 Hydroxycholecalciferol

The 25-hydroxylations of [3H]cholecalciferol and 1α-hydroxy[3H]cholecalciferol in perfused rat liver were compared. Results showed that about twice as much 1α(OH)D3 (1α-hydroxycholecalciferol) was incorporated into the liver as cholecalciferol. 25-Hydroxy[3H]cholecalciferol and 1α-25-dihydroxy[3H]cholecalciferol were not incorporated significantly. Livers isolated from vitamin D-deficient rats formed the 25-hydroxy derivatives of cholecalciferol and 1α(OH)D3 respectively linearly with time for at least 120min. The rate of 1α,25(OH)2D3 (1α,25-dihydroxycholecalciferol) production increased exactly 10-fold on successive 10-fold increases in the dose of 1α(OH)D3, suggesting that hepatic 25-hydroxylation of 1α(OH)D3 is not under metabolic control. On the other hand, the rate of conversion of cholecalciferol into 25(OH)D3 (25-hydroxycholecalciferol) did not increase linearly with increase in the amount of cholecalciferol in the perfusate. The 25-hydroxylation of cholecalciferol seemed to proceed at a similar rate to that of 1α(OH)D3 at doses of less than 1nmol, but with doses of more than 2.5nmol, the conversion of cholecalciferol into 25(OH)D3 became much less efficient, though the linear relation between the amounts of substrate and product was maintained. A reciprocal plot of data on the 25-hydroxylation of cholecalciferol gave two Km values of about 5.6nm and 1.0μm, whereas that for the 25-hydroxylation of 1α(OH)D3 gave a single Km value of about 2.0μm. These results suggest that there are two modes of 25-hydroxylation of cholecalciferol in the liver, which seem to be closely related to the mechanism of control of 25(OH)D3 production by the liver.

Determinants of glutathione efflux and biliary GSH/GSSG ratio in perfused rat liver

1989 ◽  
Vol 256 (3) ◽  
pp. G482-G490 ◽  
Author(s):  
N. Ballatori ◽  
A. T. Truong ◽  
A. K. Ma ◽  
J. L. Boyer
Keyword(s):  
Rat Liver ◽  
Transferase Activity ◽  
Gamma Glutamyl Transferase ◽  
Perfused Rat Liver ◽  
Bicarbonate Buffer ◽  
Gamma Glutamyl ◽  
Fluorocarbon Emulsion ◽  
Glutamyl Transferase ◽  
O2 Delivery ◽  
Sinusoidal Efflux

Utilizing the isolated perfused rat liver, we examined several factors influencing efflux of glutathione [reduced glutathione (GSH) and glutathione disulfide (GSSG)] into perfusate and bile, including the effects of perfusate composition, oxygen delivery to the liver, and acivicin (AT-125), an inhibitor of gamma-glutamyl transferase activity. When livers were perfused with a recirculating Krebs-Ringer bicarbonate buffer only 7-26% of released glutathione was excreted into bile, mainly in its oxidized form (71-90% as GSSG). In contrast, when 20% bovine red blood cells or 20% fluorocarbon emulsion were utilized as perfusates, biliary glutathione accounted for a larger fraction of total hepatic efflux (16-41%), and only 39-65% was excreted as GSSG. To determine whether O2 delivery to the liver could explain some of these differences, biliary and sinusoidal efflux of glutathione were measured as O2 delivery was varied by 1) increasing the perfusion flow rate, 2) altering the concentration of fluorocarbon emulsion (5, 10, and 20%), and 3) changing the PO2 (95% O2-5% CO2 vs. 50% O2-5% CO2-45% N2). Under all experimental conditions, an increase in O2 delivery was accompanied by an increase in bile flow and in the concentration and rate of glutathione efflux into bile but no significant change in sinusoidal efflux of glutathione. Hepatic tissue GSH and GSSG levels were not affected by the various treatments. When gamma-glutamyl transferase activity was inhibited with AT-125, biliary glutathione increased to levels of approximately 50% of total hepatic efflux in fluorocarbon-perfused livers, and only 24-29% of the glutathione was excreted as GSSG.(ABSTRACT TRUNCATED AT 250 WORDS)

Liver Blood Flow as a Major Determinant of the Clearance of Recombinant Human Tissue-Type Plasminogen Activator

1992 ◽  
Vol 67 (01) ◽  
pp. 083-087 ◽  
Author(s):  
A de Boer ◽  
C Kluft ◽  
J M Kroon ◽  
F J Kasper ◽  
H C Schoemaker ◽  
...  
Keyword(s):  
Blood Flow ◽  
Rat Liver ◽  
Healthy Subjects ◽  
Liver Blood Flow ◽  
Major Determinant ◽  
Tissue Type ◽  
Perfused Rat Liver ◽  
Liver Model ◽  
Type Plasminogen Activator ◽  
Proportional Change

SummaryThe influence of changes in liver blood flow on the clearance of rt-PA was studied both in healthy subjects and in a perfused rat liver model. Liver blood flow in healthy subjects was documented indirectly by the clearance of indocyanine green (ICG). Exercise reduced liver blood flow on average by 57% with a 95% confidence interval (95% Cl) ranging from 51% to 62% (n = 5) and increased plasma levels of rt-PA activity (after an i. v. infusion of 18 mg of rt-PA over 120 min) by 119% (95% Cl, 58% - 203%) and rt-PA antigen by 91% (95% Cl, 30% - 140%). In the perfused rat liver model it was shown that halving or doubling of the physiological flow rate of a perfusate, containing rt-PA caused a proportional change in the clearance of rt-PA, while the extraction of rt-PA by the liver remained similar. In conclusion, liver blood flow is a major determinant of the clearance of rt-PA. This may have important implications for dosage of rt-PA in patients with myocardial infarction.

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