Comparison of the metabolism of testosterone and methyltestosterone and their relation to the in vitro metabolism of creatine and guanidoacetic acid
Creators: name: Levedahl, Blaine H.
Publisher: name: University of Utah
Year: 2012
Subjects: Metabolism
Creatine

description: The metabolism of testosterone and methyltestosterone by liver and kidney tissue of several species has been investigated.  In the livers of all species studied there appears to be an enzyme system that requires citrate as a cofactor.  This system causes the destruction of the alpha-beta bonding which is found in ring A of many steroids.  There is also present in the livers of all species studied except the rabbit an enzyme that requires diphosphopyridine nucleotide for its activity and oxidized the alcohol group at carbon -17 to a ketone.  Kidney tissue contains the diphosphopyridine nucleotide - activated system but has very little activity on the alpha-beta conjugation.  The effect of variation of diphosphopyridine nucleotide on the metabolism of testosterone by liver mince has been investigated.  The effect noted on the metabolism of ring A was very small and errotic.  The metabolism of carbon-17 apparently requires 3 mole of diphosphopyridine nucleotide per mole of steroid for maximum oxidation.  It has been found that carbon-17 of methyltestosterone is not metabolized to form 17-ketone groups by either tissue.  The methyl grouping at carbon-17 appears to block the action of the enzyme system which otherwise catalyzes the oxidation of the alcohol group to a ketone group.  Ring A of the two steroids is metabolized by liver tissue to the same extent under similar conditions.  It is therefore concluded that the metabolism of ring A for both compounds follows the same course and is perhaps carried out by the same enzyme systems.  The alpha-beta conjugation in both compounds is destroyed only to be very slight extent in kidney tissue.  Methyltestosterone labeled in the methyl group at carbon-17 with C14 has been incubated with liver mince. No. definite compound has been completely identified to data.  However, it is clear that several products are formed during the incubation.  These included a steroid component with a melting point of 220-235° C. and some organic acid.  No single metabolic product accumulated in significant amounts.  Methyltestosterone when incubated with testosterone in ratios as high as 2:1 did not act as inhibitor to the enzyme system that oxidizes carbon-17 of testosterone.  There was no effect of either steroid on the formation of guanidoacetic acid, creatine, or creatinine by liver or kidney tissues.  The addition of diphosphopyridine nucleotide and citrate led to an increase in both "apparent" creatine and "apparent" creatinine but this was unaffected by the presence of the steroids.  When a paper chromatographic method was used to separate creatine and creatinine from other substances giving the Jaffe reaction, no increase in creatine was observed, but the marked increase in creatinine was confirmed.  It was concluded that the ration of oral to subcutaneous activity can be explained by presence of one enzyme which acts on testosterone but no on methyltestosterone.  The failure of other workers to isolate products of methyltestosterone metabolism in the urine is probably due to the number of such products, none of them 17-ketosteroids which are produced.  The base for the specific effect of methyltestosterone on the guanidoacetic acid-creatine metabolism has not yet been discovered.