Effect of propaquizafop and its free-acid derivative on lauric acid hydroxylation and peroxisomal β-oxidation in primary cultured rat, mouse, guinea pig and marmoset hepatocytes

1. Time courses for the uptake of L-lactate, D-lactate and pyruvate into isolated cardiac ventricular myocytes from guinea pig were determined at 11 degrees C or 0 degrees C (for pyruvate) in a citrate-based buffer by using a silicone-oil-filtration technique. These conditions enabled initial rates of transport to be measured without interference from metabolism of the substrates. 2. At a concentration of 0.5 mM, transport of all these substrates was inhibited by approx. 90% by 5 mM-alpha-cyano-4-hydroxycinnamate; at 10 mM-L-lactate a considerable portion of transport could not be inhibited. 3. Initial rates of L-lactate and pyruvate uptake in the presence of 5 mM-alpha-cyano-4-hydroxycinnamate were linearly related to the concentration of the monocarboxylate and probably represented diffusion of the free acid. The inhibitor-sensitive component of uptake obeyed Michaelis-Menten kinetics, with Km values for L-lactate and pyruvate of 2.3 and 0.066 mM respectively. 4. Pyruvate and D-lactate inhibited the transport of L-lactate, with Ki values (competitive) of 0.077 and 6.6 mM respectively; the Ki for pyruvate was very similar to its Km for transport. The Ki for alpha-cyano-4-hydroxycinnamate as a non-competitive inhibitor was 0.042 mM. 5. These results indicate that L-lactate, D-lactate and pyruvate share a common carrier in guinea-pig cardiac myocytes; the low stereoselectivity for L-lactate over D-lactate and the high affinity for pyruvate distinguish it from the carrier in erythrocytes and hepatocytes. The metabolic roles for this novel carrier in heart are discussed.

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Enhanced Electron Transfer and Lauric Acid Hydroxylation by Site-Directed Mutagenesis of CYP119

Journal of the American Chemical Society ◽

10.1021/ja017174g ◽

2002 ◽

Vol 124 (20) ◽

pp. 5684-5691 ◽

Cited By ~ 70

Author(s):

Laura S. Koo ◽

Chad E. Immoos ◽

Michael S. Cohen ◽

Patrick J. Farmer ◽

Paul R. Ortiz de Montellano

Keyword(s):

Electron Transfer ◽

Lauric Acid ◽

Site Directed Mutagenesis ◽

Directed Mutagenesis ◽

Acid Hydroxylation

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Inactivation of substance P and its C-terminal fragments in rat plasma and its inhibition by Captopril

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y81-096 ◽

1981 ◽

Vol 59 (6) ◽

pp. 621-625 ◽

Cited By ~ 37

Author(s):

R. Couture ◽

D. Regoli

Keyword(s):

Substance P ◽

Guinea Pig ◽

Angiotensin Converting Enzyme ◽

Free Acid ◽

Biological Activities ◽

Peptide Bond ◽

Rat Plasma ◽

Converting Enzyme ◽

Metabolic Degradation

The metabolic degradation of substance P(SP), some of its C-terminal fragments, and some analogues by rat plasma has been evaluated from the disappearance of the biological activities of these peptides on the guinea pig isolated ileum. The experiments were performed by dissolving each peptide in saline and by adding 20% (v/v) of rat plasma for incubation at 37 °C for various periods of time.It was found that SP and octapeptide 4–11 are inactivated quite rapidly and at approximately the same rate whereas SP-free acid, heptapeptide 5–11, hexapeptide 6–11, and [D-Trp8]-SP are inactivated more slowly. The replacement of Phe7 by D-Trp does not protect the undecapeptide SP from inactivation.The degradation of SP and of all the C-terminal fragments was completely blocked by Captopril at a concentration of 10 μg/mL of plasma. Under these conditions, Captopril also slightly reduced the rate of inactivation of bradykinin and of SP-free acid.These results were interpreted as indicative of the presence in rat plasma of an endopeptidase that hydrolyses a peptide bond in the C-terminal pentapeptide sequence of SP. This endopeptidase is completely inactivated by Captopril, which thus appears to be not as specific for the angiotensin-converting enzyme as it was thought to be.

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Induction of lauric acid hydroxylation and maintenance of cytochrome P-450 content by clofibrate in primary cultures of rat hepatocytes

Toxicology Letters ◽

10.1016/0378-4274(83)90372-7 ◽

1983 ◽

Vol 18 ◽

pp. 46

Author(s):

B.G. Lake ◽

T.J.B. Gray ◽

J.A. Beamand ◽

C.R. Stubberfield ◽

S.D. Gangolli

Keyword(s):

Lauric Acid ◽

Primary Cultures ◽

Rat Hepatocytes ◽

Acid Hydroxylation ◽

Cytochrome P 450

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Kinetic Analysis of Lauric Acid Hydroxylation by Human Cytochrome P450 4A11

Biochemistry ◽

10.1021/bi500710e ◽

2014 ◽

Vol 53 (39) ◽

pp. 6161-6172 ◽

Cited By ~ 23

Author(s):

Donghak Kim ◽

Gun-Su Cha ◽

Leslie D. Nagy ◽

Chul-Ho Yun ◽

F. Peter Guengerich

Keyword(s):

Cytochrome P450 ◽

Kinetic Analysis ◽

Lauric Acid ◽

Human Cytochrome ◽

Acid Hydroxylation

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The effect of high-fat diets on microsomal lauric acid hydroxylation in rat liver

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism ◽

10.1016/0005-2760(86)90104-9 ◽

1986 ◽

Vol 879 (2) ◽

pp. 209-214 ◽

Cited By ~ 24

Author(s):

Astrid Nilsson ◽

Hibret Arey ◽

Jan I. Pedersen ◽

Erling N. Christiansen

Keyword(s):

Rat Liver ◽

Lauric Acid ◽

High Fat ◽

High Fat Diets ◽

Acid Hydroxylation ◽

Fat Diets

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The Bronchodilator Activity of AY-22093, a Prostanoic Acid Derivative

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y74-001 ◽

1974 ◽

Vol 52 (1) ◽

pp. 1-7 ◽

Cited By ~ 9

Author(s):

R. Greenberg ◽

G. Beaulieu

Keyword(s):

Blood Pressure ◽

Smooth Muscle ◽

Guinea Pig ◽

Acid Derivative ◽

Prostaglandin E ◽

Significant Protection ◽

In Vitro Techniques ◽

Bronchodilator Activity

The bronchodilator activities of AY-22093, prostaglandin E2 (PGE2), and isoproterenol were compared using in vivo and in vitro techniques. In the conscious guinea pig, an aerosol of AY-22093, PGE2, and isoproterenol afforded significant protection against histamine-induced bronchospasm; AY-22093 and isoproterenol were equally effective in protecting against antigen-induced anaphylaxis. In the anesthetized guinea pig, using the Konzett and Rössler technique, PGE2 (1 μg/kg, intravenously (i.v.)) inhibited the bronchoconstriction induced by histamine (10 μg/kg, i.v.) by 63% as compared with 37% inhibition after AY-22093 (1 μg/kg, i.v.). Larger intravenous doses of PGE2 and AY-22093 (10 and 20 μg/kg) caused almost complete inhibition of the histamine-induced bronchoconstriction. The administration of PGE2 (0.5–10 μg) or AY-22093 (5–100 μg) by aerosol inhibited the bronchoconstriction induced by histamine (10 μg/kg, i.v.) by 20–70%. Maximum bronchodilator effects occurred within 3 min and lasted for as long as 30 min after either route of administration. Both compounds caused a fall in blood pressure after intravenous but not after aerosol administration. AY-22093 relaxed the guinea pig tracheal strip where tone was induced by carbachol. This relaxation was not altered by propranolol. The results indicate that AY-22093 is a bronchodilator qualitatively similar to PGE2, having a direct effect on smooth muscle but less potent than PGE2.

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