Oxygenases in Fatty Acid and Steroid Metabolism

Hámberg, Mats; Samuelsson, Bengt; Björkhem, Ingemar; Danielsson, Henry

doi:10.1016/b978-0-12-333640-8.50007-1

Cited by 24 publications

(17 citation statements)

References 278 publications

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“…One possible explanation for this discrepancy would be the existence of two different ecdysone monooxygenating enzymes in insects. Indeed, in mammals, both microsomal and mitochondrial steroid monooxygenases have been described [9]. This would imply, however, that Manduca and Schistocerca mitochondria differ notably from mammalian ones.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the fact that no enzyme activity could be observed when mitochondrial fractions were supplied with malate, isocitrate or succinate is strongly suggestive that ecdysone 20-monooxygenase is not a mitochondrial enzyme in locusts. Indeed, mitochondrial steroid hydroxylases from vertebrate tissues are located at the inside of the inner membrane [26], and need Krebs cycle intermediates to generate intramitochondrial NADPH [9], as the inner membrane of intact mitochondria is impermeable to pyridine nucleotides.…”

Section: Discussionmentioning

confidence: 99%

“…A similar enzyme system has been shown to be responsible for steroid monooxygenation in mammalian tissues [9]. The existence of xenobioticmetabolizing monooxygenases and their similarity with the vertebrate liver cytochrome P-450 system has been well documented in insect microsomes [lo].…”

Section: 24)mentioning

confidence: 99%

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Ecdysterone Biosynthesis: A Microsomal Cytochrome-P-450-Linked Ecdysone 20-Monooxygenase from Tissues of the African Migratory Locust

Durst

1978

Eur J Biochem

128

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Ecdysone 20-monooxygenase, an enzyme which convem ecdysone to ecdysterone (the major moulting hormone of insects) has been characterized in cell-free preparations of tissues from African migratory locust. The product of the reaction has been identified as ecdysterone on the basis of several microchemical derivatization and chromatographic methods.Ecdysone 20-monooxygenase activity is located primarily in the microsomal fraction which also carries NADPH cytochrome c reductase and cytochrome P-450, as shown by sucrose density gradient centrifugation.Optimal conditions for the ecdysone 20-monooxygenase assay have been determined. The enzyme has a K,,, for ecdysone of 2.7 x lo-' M and is competitively inhibited by ecdysterone Ecdysone 20-monooxygenase is a typical cytochrome P-450 linked monooxygenase : the reaction requires O2 and is inhibited by CO, an effect partially reversed by white light. The enzyme is effectively inhibited by several specific monooxygenase inhibitors and by sulfhydryl reagents, but not by cyanide ions. Ecdysone elicits a type I difference spectrum when added to oxidized microsomes.NADPH acts as preferential electron donor. The transfer of reducing equivalents proceeds through NADPH cytochrome c (P-450) reductase : ecdysone 20-monooxygenase is inhibited by cytochrome c. Both NADPH cytochrome c reductase and' ecdysone 20-monooxygenase are inhibited by NADP' and show a similar K, for NADRH.The Malpighian tubules have the highest specific activity of ecdysone 20-monooxygenase, while fat body contain most of the cytochrome P-450 and NADPH cytochrome c reductase.( K~ = 7.5 x 10-7 M).Recent studies have established the role of the prothoracic glands in the secretion of ecdysone during larval development of insects [1,2]. This steroid is however not the major moulting hormone of insect larvae. Indeed, ecdysone serves in peripheral tissues as a precursor to ecdysterone (20-hydroxyecdysone) [3] which is also biologically more potent than ecdysone in vitro in several tests of moulting hormone activity [4].Enzymes. Ecdysone 20-monooxygenase, or ecdysone, reduced flavoprotein : oxygen oxidoreductase (20-hydroxylating) (EC 1.14.14.-); NADPH-cytochrome c (P-450) reductase (EC 1.6.2.4).Trivial Names. Ecdysone, 2fi,3fl,14~~,22R,25-pentahydroxy-5p-cholest-7-en-6-one; ecdysterone or 20-hydroxy-ecdysone, 2P,3/j14a,20R,22R,25-hexahydroxy-S~-cholest-7-en-6-one. (The use of 'a-ecdysone' for ecdysone and '8-ecdysone' for ecdysterone is an abuse and should be avoided.)While it appears that the secretion of ecdysone by the prothoracic glands and the inactivation of ecdysteroids vary during larval development [5,6], it has also become clear that the relative amounts of ecdysone and ecdysterone (and other ecdysteroids?) are fluctuating [7,8]. The enzyme responsible for the conversion of ecdysone to ecdysterone, ecdysone 20-monooxygenase, thus plays a central role in the delicate hormonal balance which controls the moulting process. It was felt that a precise characterization of this enzyme was a prerequisite to studies...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Ecdysterone Biosynthesis: A Microsomal Cytochrome-P-450-Linked Ecdysone 20-Monooxygenase from Tissues of the African Migratory Locust

Durst

1978

Eur J Biochem

128

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“…Incubation of arachidonate with human platelets suspension yielded mainly thromboxane B2 and 120H-17 : 3 as well as 120H-20 : 4 [2]. Thromboxane B2 and 120H-17: 3 are also the major products in incubations of prostaglandin H2 with platelet microsomes [4,11].…”

Section: Discussionmentioning

confidence: 99%

“…Thromboxane B2 was characterized by its thin-layer chromatography mobility in system C and system BDA [4]. 120H-17: 3 was characterized by its mobility in system C and system PE [6] and after conversion to the methyl ester in chromatography system of ethyl acetate/ 2,2,4-trimethylpentane/water (50/100/100, organic phase) [2]. Malondialdehyde was measured spectrophotometrically by the thiobarbituric acid assay as described elsewhere [9].…”

Section: Following Incubations or Aggregation Experimentsmentioning

confidence: 99%

Biosynthesis of Thromboxane B₂ and 12‐l‐Hydroxy‐5,8,10‐heptadecatrienoic Acid in Human Platelets

Raz

Aharony

Kenig-Wakshal

1978

European Journal of Biochemistry

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Human platelet microsomes convert prostaglandin H2 to thromboxane B2 and 12-~-hydroxy-5,8,10-heptadecatrienoic acid (120H-17 : 3) in approximately equimolar amounts. The synthesizing activities of both products appear to go in parallel, both activities gradually decline upon storage and are equally destroyed by heat inactivation. Furthermore imidazole, a potent inhibitor of thromboxane synthetase activity, is an equally efffective inhibitor of 120H-17 : 3 formation in platelets. These results suggest that both thromboxane Bz and 120H-17: 3 are derived from a common intermediate.We propose two alternative pathways for the conversion of prostaglandin Hz to thromboxane A2 and 120H-17 : 3 in human platelets. The first pathway depicts thromboxane A2 as the common intermediate for the formation of both thromboxane B2 and 120H-17:3. In the second pathway, prostaglanding H2 is converted to an activated intermediate which is converted to either thromboxane AZ or 120H-17:3.Arachidonic-acid-oxygenated products synthesized by human platelets include three main products Trivial Names. Prostaglandin E2, 1 la,lS(S)-dihydroxy-9-ketoprosta-S-cis,l3-trans-dienoic acid; prostaglandin Fz., 9a,l Ia,lS(S)-trihydroxyprosta-S-cis,l3-trans-dienoic acid; prostaglandin D2,9a, 15(S)-dihydroxy-l1 -ketoprosta-5-cis,l3-trans-dienoic acid ; prostaglandin AI, 1S(~-hydroxy-9-ketoprosta-S-cis,Z0,13-trans-trienoic acid ; prostaglandin H2, 9a,l 1 a-epidioxy-lS(S)-hydroxy-S-cis,l3-trans-prostadienoic acid; prostaglandin Gz, 9a,l la-epidioxy-IS(S)-hydroperoxy-5-cis, 13-trans-prostadienoic acid; 120H-17 : 3, 12.~- Thromboxane Az is a powerful vasoconstrictor of the isolated rabbit aorta and induces platelet aggregation [3,4]. Its formation was suggested to play a key role in arachidonic-acid-induced platelet aggregation [3]. In contrast, no distinct physiological role has yet been observed or suggested for 120H-17:3. Our studies were undertaken in order to compare and characterize the enzymatic activities for the synthesis of thromboxane B2 and 120H-17: 3 in human platelets.

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Glyceryl-ether monooxygenase [EC 1.14.16.5]. A microsomal enzyme of ether lipid metabolism

Taguchi¹,

Armarego²

1998

Med. Res. Rev.

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Oxygenases in Fatty Acid and Steroid Metabolism

Cited by 24 publications

References 278 publications

Ecdysterone Biosynthesis: A Microsomal Cytochrome-P-450-Linked Ecdysone 20-Monooxygenase from Tissues of the African Migratory Locust

Ecdysterone Biosynthesis: A Microsomal Cytochrome-P-450-Linked Ecdysone 20-Monooxygenase from Tissues of the African Migratory Locust

Biosynthesis of Thromboxane B₂ and 12‐l‐Hydroxy‐5,8,10‐heptadecatrienoic Acid in Human Platelets

Glyceryl-ether monooxygenase [EC 1.14.16.5]. A microsomal enzyme of ether lipid metabolism

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Oxygenases in Fatty Acid and Steroid Metabolism

Cited by 24 publications

References 278 publications

Ecdysterone Biosynthesis: A Microsomal Cytochrome-P-450-Linked Ecdysone 20-Monooxygenase from Tissues of the African Migratory Locust

Ecdysterone Biosynthesis: A Microsomal Cytochrome-P-450-Linked Ecdysone 20-Monooxygenase from Tissues of the African Migratory Locust

Biosynthesis of Thromboxane B2 and 12‐l‐Hydroxy‐5,8,10‐heptadecatrienoic Acid in Human Platelets

Glyceryl-ether monooxygenase [EC 1.14.16.5]. A microsomal enzyme of ether lipid metabolism

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About

Biosynthesis of Thromboxane B₂ and 12‐l‐Hydroxy‐5,8,10‐heptadecatrienoic Acid in Human Platelets