Cortisone metabolism in liver. II. Isolation of certain cortisone metabolites

1. The metabolism of sodium cortisone 21-[35S]sulphate was investigated in rats. 2. Quantitative and qualitative experiments showed that substantial amounts of 35SO42- appeared in the urine of free-ranging rats receiving the ester. 3. Whole-body radioautograms indicated considerable biliary elimination of 35S and also pointed to the liver as the site of metabolism. 4. When female rats with bile-duct cannulae received sodium cortisone 21-[35S]sulphate approx. 70% of the dose appeared in the bile as a doubly conjugated steroid (metabolite I). This metabolite was identified as 3α-(β-d-glucopyranuronosido)- 17α-hydroxy-21-[35S]sulpho-oxy-5α-pregnane-11,20-dione. 5. When metabolite I was administered to a rat with a bile-duct cannula 90% of the dose appeared in the bile unchanged. After the administration (intraperitoneally or orally) of metabolite I to free-ranging rats considerable amounts of 35SO42- appeared in the urine. 6. The route by which 35SO42- might be produced from cortisone [35S]sulphate in free-ranging animals is discussed.

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

The metabolism of sodium cortisone 27-[35S]-sulphate in the rat

Gatehouse¹,

Roy²,

Dodgson³

et al. 1972

“…HUNTER AND R. A. MEIGS & Schuler (1953). It was demonstrated in isolated preparations of rat liver by Caspi, Levy & Hechter (1953), Fish, Hayano & Pincus (1953) and Hurlock & Talalay (1959). Mahesh & Ulrich (1959 showed that homogenates of various tissues of the rat carried out the reaction (Fig.…”

mentioning

confidence: 97%

Metabolism of 11-oxygenated steroids. Metabolism in vitro by preparations of liver

Bush¹,

Hunter²,

Meigs³

1968

100

1. The isolation and partial purification of 11beta-hydroxy steroid dehydrogenase from rat and guinea-pig liver microsomes has been achieved by conventional methods. 2. The efficiency of different 11-oxygenated steroids as substrates has been examined. The relative efficiencies confirm in the main the stereochemical theory of the enzyme-coenzyme-substrate complex that was proposed earlier on the basis of studies in vivo. Delta(4)-3-Ketones and 5alpha-hydrogen steroids are readily metabolized by the enzyme. 5beta-Hydrogen steroids and Delta(4)-3-ketones with certain large alpha-substituents are metabolized to a limited extent or not at all. Halogen substitution in the 9alpha-position enhances the rate of reduction of 11-ketones but blocks the oxidation of the related 11beta-ols. 3. 9alpha-Fluorocortisol is a competitive inhibitor of the oxidation of cortisol, but 9alpha-fluorocortisone is reduced at five to ten times the initial velocity of cortisone. 4. 11beta-Hydroxy steroid dehydrogenase activity has been found in liver microsomes of rat, guinea pig, rabbit and calf. 5. Relative substrate efficiencies and K(m) values are similar in whole (debris-free) homogenates, washed microsomes and acetone-dried powders of washed microsomes. 6. A variety of conditions have been examined for the observation of 11beta-hydroxy steroid dehydrogenase activity. NADP(H) is an efficient and NAD(H) a very poor coenzyme for the reaction.

“…In this paper evidence will be given that this substance is allotetrahydrocortisol (3a:11 l,: 17oc: 21 -tetrahydroxy- and that it is a normal metabolite of cortisol and cortisone in man. This substance has long been known as a component of adrenal-gland extracts (Wintersteiner & Pfiffner, 1935;Reichstein, 1936;Mason, 1936Mason, ,1938Kuizenga, 1939) andrecentlyhas been shown to be a metabolite of cortisol in isolated perfused rat livers (Caspi, Levy & Hechter, 1953;Caspi & Hechter, 1954). It is peculiar in being one of the few natural C21 steroids of animal origin having the axial configuration of its 3-hydroxyl group.…”

mentioning

confidence: 99%

The excretion of allotetrahydrocortisol in human urine

Bush

Willoughby

1957

135

hypothesis that A. xylinum is a phylogenetic ancestor of A. 8uboxydan8 thus might imply only that A. xylinum has been able to undergo consecutive loss mutations of two non-essential enzyme systems. An opposing view, namely that evolution proceeded from a simple state to a more complex one, may be more attractive on philosophical grounds. In that case, the interesting possibility has to be considered that the ancestor of Acetobacter was equipped with a mutative potential so broad as to comprise within its range two enzyme systems (respectively for cellulose synthesis and acetate oxidation) which are facultative in Acetobacter but have elsewhere assumed cardinal roles in cellular survival. SUMMARY 1. A cell-free extractofAcetobacterxyltinumfailed to form cellulose from a range of tested substrates. 2. The extract (with added phenazine methochloride) oxidized glucose aerobically to gluconate. When this system was further supplemented with diphosphopyridine nucleotide, it oxidized gluconate to oxogluconate (largely 2-oxogluconate). 3. The extract with adenosine triphosphate oxidized glucose aerobically to carbon dioxide. The extract contained kinases (glucokinase and gluconokinase), phosphoglucomutase, a complete pentosecycle set of enzymes, and a set of enzymes by which triose phosphate could be converted into pyruvate. 4. A scheme of altemate pathways for glucose metabolism that can be operated in an A. xyltinum cell is proposed. The scheme shows a pentose cycle which has several ports of entry and exit. The latter lead from the pentose cycle into a citrate cycle. 5. Biochemical evolution in the genus Acetobacter is briefly discussed. Note added in proof.