IPHY 4440 1t Edition Lecture 5Outline of Current Lecture II. SPRMsIII. NomenclatureIV. SteroidgenesisV. Synthesis of cholesterol Current LectureI. SPRMs“Selective progestogen receptor modulators” aka “anti-progesterone”(e.g. Asoprisnil ZK299 and Mifepristone RU 486)II. NomenclatureA. Double bond positions One –eneTwo –dieneDouble bond between carbons 4 & 5 4-eneDouble bond between carbons 5 & 10 5(10)-eneEx: androst-5(10)-ene meaning 19 carbons since androgen B. Hydroxyl group –OHPrefix: 17-hydroxy-androstane Suffix: androstan-17-ol C. Ketone group: =OPrefix: 17-keto-androstaneSuffix: androstane-17-one D. SteroidogenesisSynthesis of cholesterol i. Human genes are italicized CYP11A1 (cytochrome P450 family)ii. Enzyme would be CYP11A1iii. (e.g. HSD3B1 3BHSDI)E. CYP11A1= cholesterol side chain cleaving enzyme In this class, we will call it P450 SCC = a cytochrome mitochondrial enzyme- Basically just clip off the side chain These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.- P450 will be used for ALL cytochrome enzymes and the subscript describes what it does- Non-cytochrome enzymes will be named 3B-HSD (B meaning beta) III. Synthesis of cholesterolRate-limiting enzyme HMG-CoA reductaseSubstrate: Acetyl CoA Acetyl CoA cholesterol IV. Synthesis of progestogensCatabolic process: C27 C 21 1st steroid that cholesterol breaks down is a progestogen - P450 is an enzyme that is always inthe mitochondria VI. Cholesterol enters the mitochondria StAR: steroidogenic acute regulatory protein Cholesterol inner membrane (into mitcochondria) Rate-limiting step Not an enzyme Cholesterol pregnenolone (C21) * all occurs in mitochondira because of the enzyme P450SCCVII.Δ5 Pathway: pregnenolone x DHEA- all 5-ene steroids (double bond occurs on all 5 &6)- Occurs in adrenal cortex & ovary Δ4 Pathway: pregnenolone progesterone (enzyme: 3B-HSD) all 4-ene Δ4 Pathway: progesterone (X) androstenedione testosterone Weak androgen: androstenedion( 2 ketones)Strong androgen: testosterone (1 ketone) VIII. Testosterone (T) 5a-reductase dihydrotestosterone
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