Competitive Inhibition of Adrenal Δ5-3β-Hydroxysteroid Dehydrogenase and Δ5-3-Ketosteroid Isomerase Activities by Adenosine 3',5'-Monophosphate

McCune, Ronald W.; Roberts, Sidney; Young, Paul

doi:10.1016/s0021-9258(18)62929-1

Cited by 60 publications

(1 citation statement)

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“…This observation would account for the inhibition ofcholesterol biosynthesis and the accumulation of the C-4 carboxylic acid steroid derivative that occurs in the presence of cyclic AMP. It is noteworthy that cyclic AMP has been shown to act as an inhibitor of A5-3fl-hydroxy steroid dehydrogenase in adrenal cortex (Koritz, Yun & Ferguson, 1968;McCune, Roberts & Young, 1970) and ovarian tissue (Sulimovici & Boyd, 1969) and of a mitochondrial dehydrogenase from adrenal cortex (Akhtar, Bloxham & Poat, 1970).…”

Section: Discussionmentioning

confidence: 99%

Studies on the mechanism and regulation of C-4 demethylation in cholesterol biosynthesis. The role of adenosine 3′:5′-cyclic monophosphate

Bloxham

Wilton

Akhtar

1971

Biochemical Journal

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1. An assay for demethylation has been developed based on the release of tritium from 4,4-dimethyl[3alpha-(3)H]cholest-7-en-3beta-ol (II). 2. The maximum release of (3)H from 3alpha-(3)H-labelled compound (II) in a rat liver microsomal preparation occurs in the presence of NADPH and NAD(+) under aerobic conditions. 3. Incubation of 3alpha-(3)H-labelled compound (II) with NADPH under aerobic conditions leads to the formation of a 3alpha-(3)H-labelled C-4 carboxylic acid. This compound undergoes dehydrogenation on subsequent anaerobic incubation with NAD(+). 4. The (3)H released from the steroid was located in [4-(3)H]nicotinamide and the medium. Incubation with synthetic [4-(3)H(2)]NADH gave a similar result. 5. In the presence of glutamate dehydrogenase and alpha-oxoglutarate part of the (3)H released from the steroid was transferred to glutamate. 6. A series of 3-oxo steroids were reduced equally well by [4-(3)H(2)]NADH and [4-(3)H(2)]NADPH. The reduction of 5alpha-cholest-7-en-3-one was shown to use the 4B H atom from the nucleotide. 7. 3':5'-Cyclic AMP was shown to be a competitive inhibitor of the 3beta-hydroxy dehydrogenase enzyme in the demethylation reaction.

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