Metabolic Pathways of Steroids Department of Clinical Biochemistry, King’s College Hospital, London CH OH BILE 3 CH C O O H CH 2 C O O H CH 2 OH O O O 2 ACIDS CH C -O H -C HCOH + CH -C -O H 3 CH 3 CH C -S -C oA CH C - CH C -S -CoA 3 3 3 2 CH - CH2 CH C -S -C oA CH 2 CH O H OH ACETYL-COENZYME-A ACETOACETYL-COENZYME-A 2 2 O ISOPRENOID UNIT MEVALONIC ACID(3:5- SQUALENE HO HO FROM MAVALONIC ACID LANOSTEROL H ZYMOSTEROL DESMOSTEROL HO MONO-COENZYME A ESTER DIHYDROXY-3-METHYL H HO HO OF 3-HYDROXY-3-METHYL PENTANOIC ACID) CH3 CHOLESTEROL ( ANDROSTENEDIOL GLUTARIC ACID SO4) 20 α-HSD CH3 20,22-lyase HO (∆A2 17 α) 17 α-HSD ANDROSTENEDIOL-17 β CH HCOH PRENENETRIOL( ∆P3) CH 3 CH 3 CO 3 17 β-HSD HCOH O O CO 20 α-HSD CO OH OH OH 16 α-OHase CH 17-OHase 3 HO 17,20-lyase CH3 CH 3β-HSD/ ∆4,5isomerase 3 PREGNENEDIOL( ∆P2) HO HO HCOH O CO O 16 α-HYDROXY- ( SO ) HO HO 16 α-HYDROXYDEHYDRO- 20 α-DIHYDRO- PREGNENOLONE 4 PROGESTERONE CO 17 α-HYDROXY- EPIANDROSTERONE PROGESTERONE CH3 CH ( DEHYDRO- 20 α-HSD 3 PRENENOLONE ( ) O 16 α-OHase SO4 EPIANDROSTERONE (SO ) (16 α-DHA) 20 α-HSD O O 4 3α-HSD/ CO HCOH 5β-reductase OH OH HO HO 3α-HSD H CH 3αHSD/ CH 3 20 α-HSD 3 H CH OH 21-OHase 5β-reductase 17,20-lyase 2 CH O 3β-HSD/ ∆4,5isomerase PREGNANOLONE 3 17-OHase HO HO CO PROGESTERONE CH3 O PREGNANEDIOL HCOH HO HO H H CO DEHYDROEPI- CO 11 β-OHase H H AETIOCHOLANOLONE ANDROSTERONE (DHA) OH CO 17 α-HYDROXY- 5β-ANDROSTANEDIONE 5β-reductase 20 α-HSD OH PREGNANOLONE PREGNANETRIOL 17 β-HSD HO CH HO 3 H O 17,20-lyase 3β-HSD/ ∆4,5isomerase H OH O OH 11 β-HYDROXY- CH O 21-OHase 6β-HSD 3 CH OH O CO 6α-HYDROXY- DEOXYCORTICOSTERONE PROGESTERONE CH OH CH OH 2 6α-HYDROXY- 17 α-OHase 17 α-HYDROXY 2 2 PREGNANOLONE OH PREGNANEDIOL CO PROGESTERONE O HCOH 3α-HSD/ HO CO CO OH 5α-reductase 5β-reductase OH OH OH OH 3α-HSD/ 5β-reductase HO 11 β-OHase CH OH 20 α-HSD O 2 11 β-OHase HO O O 21-OHase O ANDROSTENEDIONE HO HO H 6-OXOPREGNANOLONE CO 21- DEOXYCORTISOL O CH3 H H ANDROSTENETRIOL 11-DEOXYCORTISOL (∆A3) CH2OH TERTRAHYDRO 'S' HEXAHYDRO 'S' 5α-ANDROSTANEDIONE 11 β-OHase CO 11 β-HSD (SUBSTANCE S) O 3α-HSD/ 19 -OHase CH OH OH 5β-reductase CO 17 β-HSD CH OH CH OH 2 OH 2 2 HO 3α-HSD CH 3 OH CH OH CO CO 2 O CO HO CH OH OH HCO CO CH2OH O O HO H HOCH O OH Aldosterone synthase O HO HO OH TETRAHYDRO- HO OH 11 β-HSD CO O DEOXY- 21- DEOXYCORTISONE O OH HO OH CORTICOSTERONE CORTISOL 11 β-HSD O OH 3α-HSD/ (COMPOUND F) 20 β-HSD O CH OH CH3 O 2 5β-reductase ALDOSTERONE O CORTICOSTERONE HO 5β-reductase O HO O O (hemi-acetal form) ALDOSTERONE (COMPOUND B) CO CO H O O H H OO 19-HYDROXY- 3α-HSD/ 3β-HSD/ O 16 α-HYDROXY- O HO 21-DEOXYTETRA- 20 β-DIHYDRO- 11 β-HYDROXY- ANDROSTENEDIONE 5α-reductase 5β-reductase O CORTISONE ANDROSTERONE ANDROSTENEDIONE TESTOSTERONE HYDROCORTISOL CORTISONE 5β-ANDROSTANOLONE TESTOSTERONE CH2OH CH OH CH OH 2 CH OH 3α-HSD/ 2 3α-HSD/ 6β-OHase 20 β-HSD 2 (COMPOUND 'E') 3α-HSD/ CH OH 5α-reductase 19 -OHase CO 5β-reductase 5α-reductase 2 aromatase CO CO 5β-reductase 3α-HSD HCO CH OH HO HO 2 HOCH CH2OH HCO HO HCO HO CO OH HO O H OH 3α-HSD 3α-HSD/ OH OH OH O II-DEHYDROCORTICOSTERONE 21-DEOXYTETRA- CO 5β-reductase CO 5α-reductase OH (COMPOUND A) HYDROCORTISONE HO OH OH O OH OH 3α-HSD/ HO 3α-HSD/ 5α-reductase 20 α-HSD H HO HO 5β-reductase O H H HO HO 5α-TETRAHYDRO- HO O O TETRAHYDRO- 3β-TETRAHYDRO- H H H ALDOSTERONE 20 β-DIHYDRO- HO ALDOSTERONE ALDOSTERONE O 19-HYDROXY- CORTISOL H 5β-ANDROSTANE- CH OH CH3 OH 5α-TETRAHYDROCORTISONE 5α-ANDROSTANOLONE OESTRIOL CH OH CH OH CH OH 2 TESTOSTERONE 2 2 2 TETRAHYDROCORTISONE 3α, 17 β-DIOL (DIHYDROTESTOSTERONE) HCOH 6β-HYDROXY- 3α-HSD/ aromatase CO O CORTISOL 3α-HSD/ CO CO CO 20 β-HSD O HO 5α-reductase 5β-reductase 20 α-HSD 20 α-HSD 20 β-HSD HO HO O 3α-HSD CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH aromatase 17 β-HSD HO CO HOCH OH HO CO HCOH HOCH HCOH HO H HO HO HO H HO OH O O H H H OH O OH O O OH O 20 β-HSD OH OH allo-TETRAHYDRO 'B' TETRAHYDRO 'B' TETRAHYDRO 'A' 5α-TETRAHYDRO 'A' 11-OXO-PREGNANETRIOL 16α−ΟΗ ase OH HO HO HO HO 20 β-HSD H HO HO HO H HO 20 β-HSD H H H TETRAHYDROCORTISOL H H HO CH OH 5α-TETRAHYDRO α− CORTOLONE 5α-ANDROSTANE- OESTRONE CH OH 2 β-CORTOLONE 16 α-HYDROXY- 2 CORTISOL 5α-CORTOLONE 20 β-5 α-CORTOLONE 3α, 17 β-DIOL CH2OH OESTRONE HOCH 20 β-HSD HOCH 20 α-HSD 17,20-lyase 17 β-HSD HOCH HO HO 17,20-lyase 17,20-lyase 17,20-lyase HCO 20 α-HSD 20 β-HSD HO OH CH2OH O OH CH OH CH2OH O O CH OH 2 O 2 O HOCH OH HO HCOH HO HO HOCH HO H HCOH HO OH H HO HO HO H OH OH HEXAHYDRO 'B' HO HEXAHYDROALDOSTERONE 5a-HEXAHYDRO 'B' 17 β-HSD HO HO HO HO HO H 16 β-HYDROXY- EPI-OESTRIOL H OESTRADIOL-17 β KEY 11-OXO-ANDROSTERONE OESTRONE HO H HO HOO 11-OXO-AETIOCHOLANOLONE HO H H Catabolic pathways H 20 β, 5 α-CORTOL α− CORTOL 5α-CORTOL β-CORTOL 3α-HSD/ 5α-reductase Anabolic pathways 17,20-lyase 17,20-lyase 17,20-lyase 17,20-lyase O O O 11 β-HSD HO O Major hormonal steroids HO O Major urinary metabolites HO H OH H 11-OXO-ANDROSTENEDIONE 11 β-HYDROXY- ANDROSTERONE 11 β-HYDROXY- Intermediates AETIOCHOLANOLONE 3α-HSD/ 3α-HSD/ 5α-reductase 5β-reductase Credits Produced by Stephanie Wright based on a chart published circa 1970 by GLAXO LABORATORIES LTD with editing by Norman Taylor, from an initial idea by Kristine Moore. 1.