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Biomedical subjects

J Jarabak

Publications and source records attributed to J Jarabak.

At least 37 records · Page 2Linked to original sources
PubMed1982

The purification and characterization of a prostacyclin dehydrogenase from rabbit kidney.

A highly purified NADP-linked 15-hydroxyprostaglandin (prostacyclin) dehydrogenase has been isolated from rabbit kidney. This enzyme has a molecular weight of 56,000-62,000 and is composed of two subunits which are presumably identical. It is not a flavoprotein. Fluorometric titrations with NADPH revealed that the cofactor was bound to the free enzyme with a dissociation constant of 0.04 microM. The results of kinetic studies were compatible with either a random mechanism or an ordered mechanism with NADP binding first. Although this enzyme oxidizes prostacyclin more rapidly than any other prostaglandin, it reduces 4-nitrobenzaldehyde, phenanthrenequinone, and menadione more rapidly than it oxidizes prostacyclin.

Amino Acids↗
PubMed1981

An NADP-linked prostacyclin dehydrogenase in rabbit kidney.

An NADP-linked 15-hydroxyprostaglandin dehydrogenase specific for prostacyclin was purified 1,300-fold from rabbit kidney. Prostaglandins E2, F2 alpha, and 6-keto PGF1 alpha and thromboxane B2 were oxidized by the purified enzyme with rates of reaction less than 4% that of PGI2. Unlike other rabbit kidney NADP-linked 15-hydroxyprostaglandin dehydrogenases, this enzyme catalyzes oxido-reduction more rapidly at the 15- position than at the 9- position and does not utilize NAD as a cofactor. It has a molecular weight of 62,000 and migrates on polyacrylamide disc gel electrophoresis as a single diffuse band. The reaction product was identified by thin-layer chromatography as 6,15-diketo PGF1 alpha. Prostacyclin dehydrogenase is the first 15-hydroxyprostaglandin dehydrogenase described which is specific for the metabolism of prostacyclin.

6-Ketoprostaglandin F1 alpha↗
PubMed1980

Early steps in prostaglandin metabolism in the human placenta.

The activities of the enzymes catalyzing in the early steps in prostaglandin metabolism (the nicotinamide adenine dinucleotide [NAD]-linked 15-hydroxyprostaglandin dehydrogenase, the nicotinamide adenine dinucleotide phosphate [NADP]-linked 15-hydroxyprostaglandin dehydrogenase, and the 15-ketoprostaglandin delta 13 reductase) were measured in homogenates of term placenta. The NAD-linked enzyme possesses the highest activity of the three. The NADP-linked enzyme has much lower activity and probably acts physiologically as a 9-ketosprostaglandin reductase rather than as a 15-hydroxyprostaglandin dehydrogenase. Placental homogenates contain a low-molecular-weight, heat-stable inhibitor of the NADP-linked enzyme. The reaction catalyzed by the 15-ketoprostaglandin delta 13 reductase is the rate-limiting step. Analysis of the activity of these enzymes has shown that there is no significant relationship between them; furthermore, whether the placentas are from spontaneous single or twin deliveries, induced deliveries, or cesarean sections (in labor or not in labor) does not have a significant effect on the activity of the NAD- or NADP-linked dehydrogenases.

15-Oxoprostaglandin 13-Reductase↗
PubMed1980

Partial isolation and characterization of the 15-hydroxyprostaglandin dehydrogenases and 9-ketoprostaglandin reductases in rabbit kidney.

Three types of 15-hydroxyprostaglandin dehydrogenase were identified in rabbit whole kidney homogenate when the centrifuged homogenate was sequentially fractionated by ammonium sulfate precipitation, DEAE-cellulose and Matrex Gel Blue A chromatographies, and Sephadex gel filtration. The first type is not adsorbed to DEAE-cellulose (peak 1). It catalyzes oxidoreduction of prostaglandins at both the C-15 and C-9 positions, is more active with NADP than NAD, is inhibited by indomethacin and ethacrynic acid, and migrates as three bands on disc gel electrophoresis. The second type is adsorbed to DEAE-cellulose (peak 2). It also migrates as multiple electrophoretic bands, has similar catalytic actions and co-factor requirements as the peak 1 enzyme and is inhibited by indomethacin and ethacrynic acid. A third type of 15-hydroxyprostaglandin dehydrogenase is also adsorbed to DEAE-cellulose but is partially separable from the other peak 2 enzymes on Matrex Gel Blue A and differs from those enzymes in preferentially oxidizing PGI2. It migrates as a single electrophoretic band and is also inhibited by indomethacin and ethacrynic acid.

Animals↗
PubMed1979

Comparison of substrate specificities of the human placental NAD- and NADP-linked 15-hydroxyprostaglandin dehydrogenases.

A study of the relative activity of the purified placental NAD- and NADP-linked 15-hydroxyprostaglandin dehydrogenases with various prostaglandins and thromboxane B2 (TxB2) suggests that most, if not all, oxidation in the placenta of the 15-hydroxyl group of prostaglandins of the A, E, and F series as well as PGI2 (prostacyclin) and 6-keto PGF1 alpha is catalyzed by the NAD-linked enzyme. Prostaglandin B1 is an excellent substrate for the NADP-linked enzyme. Despite the conformational similarities between PGB1 and PGI2, the latter molecule is a poor substrate for the NADP-linked enzyme. Thromboxane B2 is not oxidized by the NAD-linked enzyme and is oxidized slowly by the NADP-linked enzyme.

Female↗
PubMed1975

Interactions between prostaglandin analogues and a receptor in bovine Corpora lutea. Correlation of dissociation constants with luteolytic potencies in hamsters.

The dissociation constants for the interactions between some prostaglandin analogues and a prostaglandin F2 receptor in bovine corpora lutea were determined. These values were compared to the antifertility potencies of these compounds in hamsters and the rates of metabolism by 15-hydro-syprostaglandin dehydrogenase. The most active analogues with regard to both affinity for the receptor and luteolytic potency were 17-phenyl-18, 19, 20-trinorprostaglandin F2alpha and 15-methylprostaglandin F2alpha. The alkyl side chain of prostaglandins could be modified considerably without altering the affinity for the receptor. In this way metabolism by 15-hydroxyprostaglandin dehydrogenase could be blocked. Some of these compounds -ad greatly increased luteolytic effects. Substitution of a phenyl group for the 3 terminal carbon units of the alkyl side chain of prostaglandins increased both the affinity for the receptor and the luteolytic activity in vivo. 7-oxa-13-prostynoic acid, an antagonist of the luteolytic effect of prostaglandin F2alpha in vivo was a weak competitive inhibitor of the interation between prostaglandin F2alpha and the receptor.

Animals↗
PubMed1975

Studies on a 15-hydroxyprostaglandin dehydrogenase from human placenta. Purification and partial characterization.

A 15-dyroxyprostaglandin dehydrogenase has been purified from human placenta to apparent monodispersity. The reaction catalyzed by this enzyme is freely reversible with an equilibrium constant of approximately 6.5 times 10-8 M. The activation energy is 9900 calories per mol. The molecular weight of the enzyme determined by gel filtration is 51,500; sodium dodecyl sulfate disc gel electrophoresis gives a value of 42,000. No evidence was obtained for the existence of multiple forms of the enzyme or for subunits.

Alcohol Oxidoreductases↗