Metabolism of Bioactive Endogenous and Exogenous Compounds Oxidation Dehydrogenases Oxidases Cytochrome P450 enzymes Reduction Dehydrogenases Reductases Conjugation Sulfotransferases 3´-Phosphoadenosine 5´-phosphosulfate (PAPS) 3´,5´-adenosine bisphosphate sulfotransferase R OH R O S O O O O S O O O OH O CH 2 O N N N N NH 2 P O O O P O O O 3´-Phosphoadenosine 5´-phosphosulfate (PAPS)
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Metabolism of Bioactive Endogenous and Exogenous Compounds Oxidation Dehydrogenases Oxidases Cytochrome P450 enzymes Reduction Dehydrogenases Reductases Conjugation Sulfotransferases
3´-Phosphoadenosine5´-phosphosulfate
(PAPS)
3´,5´-adenosinebisphosphate
sulfotransferaseR OH R O S
O
O
OO S
O
OO
OHO
CH2O
N
N N
N
NH2
P
O
O
O
PO O
O
3´-Phosphoadenosine5´-phosphosulfate
(PAPS)
Glucuronases
O
N
HN
O
O
P
O
OO
OHOH
CH2OP
O
O
O O H
OH
OH
O
CH2HO
P
O
O
O O
α-Glucose-1-phosphate
P
O
O
O
Uridine Triphosphate(UTP)
+H
UDP-GlucosePyrophosphorylase N
HN
O
O
O
OHOH
CH2OP
O
O
O H
OH
OH
O
CH2HO
P
O
O
O O
UDP-Glucose
+H
O P
O
O
OHP
O
O
O
UDP-Glucosedehydrogenase
2 NAD+
H2O
2 NADH
N
HN
O
O
O
OHOH
CH2OP
O
O
O H
OH
OH
O
CO
P
O
O
O O
UDP-Glucuronic acid
H
O
UDP-glucuronosyltransferase
R OH
UDPUDP-Glucuronic acid
O H
OH
OH
O
CO
OH
O
R
Steroid Biosynthetic Pathways
HO Cholesterol
1
2
34
56
7
8
9
10
11
12
13
14 15
O
HO Pregnenolone
1617
18
19
20
2122
23
24
25
26
27
O
O
O
O
O
O
O
O
OH
OH
OH
HO
HO
O
O
O
O
O
O
O
OH
OH
HO
O
HO
OH
OH
OH
OH
O
HO
O
O
HO
O
O
OH
O
OH
HO
OH
O
O
S
O
O
O
P450scc
P45011β
3β-Hydroxysteroid Dehydrogenase/∆5-∆4-isomerase
P45
0 17 α
P45
0 17 α
P45021
P45018
P45018
P45
0 aro
m
17β-Hydroxysteroid Dehydrogenase
5α-Reductase
17α-Hydroxy-Pregnenolone
17α-Hydroxy-ProgesteroneProgesterone
Deoxycorticosterone
Corticosterone
Aldosterone
Dehydroepiandrosterone(DHEA)
DHEA-Sulfate
Deoxycortisol
Cortisol
Androstenedione
Testosterone
Dihydrotestosterone(DHT)
Estradiol
Estrone
Sulfotransferase
*
*
*
*
* – Denotes mitochondrial enzyme
P450scc (cholesterol side-chain cleavage enzyme)*
P45017α (17α-hydroxylase/lyase)
P45021 (21-hydroxylase)
P45011β (11β-hydroxylase)*
P45018 (18-hydroxylase)*
P450arom (aromatase)
Steroid Nomenclature
Steroid derivatives
Cholestane (C27) Pregnane (C21) Androstane (C19) Estrane (C18)
HO Cholesterol (cholest-5-ene-3β-ol)
1
2
34
56
7
8
9
10
11
12
13
14 15
1617
18
19
20
2122
23
24
25
26
27
HO
OH
OH
O
OH
H
Cholic acidHO
OHO
OH
H
Deoxycholic acidHO
OHO
NH
H
Taurocholic acid
SO
OHO
Steroid Metabolism
NAD(P) NAD(P)H
11β-hydroxysteroiddehydrogenase
HO OH
O
OH
OCortisol
OH
O
OH
OCortisone
O
HO OH
O
OH
O
5α-reductase
3a-hydroxysteroiddehydrogenase
NADPH
NADP
H
5α-dihydrocortisol
HO OH
O
OH
HOH
Tetrahydrocortisol
5β-reductase
HO OH
O
OH
OH
3α-hydroxysteroiddehydrogenase
NADPH
NADP
HO OH
O
OH
HOH
3a-Tetrahydrocortisol
NADPH
NADP
20α-hydroxysteroiddehydrogenase
HO OH
OH
OH
HOH Cortol
O
O
OH
HO
O
Aldosterone
O
O
OH
O
HO
Aldosterone
Catecholamine Synthesis
Adrenal Medulla
OH
H3N
OO
Tyrosine
Tyrosinehydroxylase
[tetrahydrobiopterin]
NADPH NADP
OH
H3N
OO
OH
DOPA
CO2
DOPA decarboxylase
[PLP]
OH
H3N
OH
Dopamine
Dopamineβ-hydroxylase
Ascorbicacid
Dehydro-ascorbicacid
OH
H3N
OH
OH
Norepinephrine
S-adenosyl methionine
O
OHOH
CH2
N
N N
N
NH2
SO
O
NH3
CH3
S-adenosyl methionine
OH
H2N
OH
OH
Epinephrine
PhenylethanolamineN-methyltransferase
(PNMT)
CH3
S-adenosylhomocysteine
TyrosineTyrosine
hydroxylase[tetrahydrobiopterin]
NADPH NADP
DOPA
CO2
DOPA decarboxylase
[PLP]
Dopamine
Norepinephrine
S-adenosylmethionine
Epinephrine
PhenylethanolamineN-methyltransferase
(PNMT)
S-adenosylhomocysteine
Dopamine
Dopamineβ-hydroxylase
Ascorbicacid
Dehydro-ascorbicacid
Norepinephrine
Epinephrine
Cytoplasm
Secretory
Vesicle
Normetanephrine
Metanephrine
Catecholamine Breakdown
Catecholamine Breakdown
OH
H3N
OH
OH
Norepinephrine
Monamine Oxidase A[flavin]
O2 NH3
H2O2 OH
O
OH
OH
3,4-dihydroxy-phenylglycoaldehyde
H
Aldehydereductase
NADPH NADP
OH
OH
OH
3,4-dihydroxy-phenylglycol
HO
Nerve termini
OH
H3N
OH
Dopamine
Monamine Oxidase B[flavin]
OH
OH
H
O
O2 NH3
H2O2
3,4-dihydroxyphenylacetaldehyde
Aldehydereductase
NADPH NADP
OH
OH
3,4-dihydroxy-phenylethanol
HO
OH
H3N
OH
OH
Norepinephrine
S-adenosylmethionine
S-adenosylhomocysteine
Catechol-O-MethylTransferase
OH
H2N
OH
OH
Epinephrine
CH3
S-adenosylmethionine
S-adenosylhomocysteine
Catechol-O-MethylTransferase
OH
H3N
O
OH
Normetanephrine
CH3
OH
H2N
O
OH
Metanephrine
CH3
CH3
Peripheral tissues
MonamineOxidaseA
[flavin]
OH
O
O
OH
3-methoxy-4-hydroxy-phenylglycoaldehyde
H
CH3
Aldehydereductase
NADPH
NADP
OH
O
OH
3-methoxy-4-hydroxy-phenylglycol
CH3
HO
O2
O2
NH2
H2O2H3C
NH3
H2O2
OH
O
O
OH
3-methoxy-4-hydroxy-mandelic acid
(Vanillylmandelic acid)(VMA)
OH
CH3
OH
O
OH
3-methoxy-4-hydroxy-phenylglycol
CH3
HO
NAD NADH
Alcoholdehydrogenase
OH
O
O
OH
3-methoxy-4-hydroxy-phenylglycoaldehyde
H
CH3
OH
O
3-methoxy-4-hydroxy-phenylethanol
HO
NAD NADH
Alcoholdehydrogenase
CH3
OH
O
O
3-methoxy-4-hydroxy-phenylacetaldehyde
H
CH3
NADH
Aldehydedehydrogenase
NADH
Aldehydedehydrogenase
Liver
NAD+ H2O
NAD+ H2O
OH
O
O
3-methoxy-4-hydroxy-phenylacetic acid
(Homovanillic acid)
OH
CH3
Consequences
O
O
N
CH3
CH3
O
N
CH3
O CH3
Meperidine(Demerol)
1-Methyl-4-propionoxypiperidine
(MPPP)
H+
HeatN
CH3
N-Methyl-4-phenyl1,2,3,6 tetrahydropyridine
(MPTP)
MonoamineoxidaseB
N
CH3
MPDP+
N
CH3
1-Methyl-4-phenylpyridinium
(MPP )+
N
HH3C
CH3
Selegiline
HO
HONHH3C
OH
O
CarbidopaNH2
HO
HO
NO2
C
N
O
CH3
CH3
NEntacapone
Acetaminophen Metabolism
UDP-Glucuronic acid
O
OH
OH
OH
C O
O N
NH
O
O
P
O
OO
OHHO
CH2OP
O
O
O
O
O
OH
OH
OH
C O
O
O
NHCH3
O
NHCH3
O
HO
Acetaminophen
N
NH
O
O
P
O
OO
OHHO
CH2OP
O
O
OO
O P
O
O
O
O S
O
OO
OH
CH2O
N
N N
N
NH2
P
O
O
O
3´-phosphoadenosine5´-phosphosulfate (PAPS)
glucuronyltransferase
sulfotransferase
NHCH3
O
HO
Acetaminophen
O S
O
O
O NHCH3
O
O P
O
O
O
O
OH
CH2O
N
N N
N
NH2
P
O
O
O
UDP
adenosine3´,5´-bisphosphate
NHCH3
O
HO
Acetaminophencytochrome P450
(CYP2E1,CYP1A2,CYP2D6)
NH3C
O
OHHO
NH3C
O
O
Acetimidoquinone
SpontaneousH2O
HN
O
HN
O
O
OH3N
O O
HS
γ-Glu
Cys Gly
Glutathione(reduced form)HN
O
HN
O
O
OH3N
O O
S
HNH3C
O
OH
Cys-Protein
S
HNH3C
O
OHProtein-Cys-SH
Spontaneous
Spontaneous
Cytochrome P450 Enzymes in Humans (from http://drnelson.uthsc.edu/human.P450.table.html) Family Known
genes Comments
CYP1 CYP1A1 CYP1A2 CYP1B1
Xenobiotic and endogenous bioactive catabolism, carcinogen activation
CYP2 CYP2A6 CYP2A7 CYP2A13 CYP2B6 CYP2C8 CYP2C9 CYP2C18 CYP2C19 CYP2D6 CYP2D7 CYP2E1 CYP2F1 CYP2J2 CYP2R1 CYP2S1 CYP2U1 CYP2W1
Xenobiotic and endogenous bioactive catabolism
CYP3 CYP3A4 CYP3A5 CYP3A7 CYP3A43
Xenobiotic and endogenous bioactive catabolism
CYP4 CYP4A11 CYP4A22 CYP4B1 CYP4F2 CYP4F3 CYP4F8 CYP4F11 CYP4F12 CYP4F22 CYP4V2 CYP4X1 CYP4Z1
Fatty acid hydroxylation
CYP5 CYP5A1 Platelet thromboxane A synthase 1 CYP7 CYP7A1
CYP7B1 7A1 is liver enzyme: 7α-hydroxylase; catalyzes the main regulated step in bile acid synthesis 7B1 is non-liver, and may be involved in steroid metabolism
CYP8 CYP8A1 CYP8B1
8A1 is prostaglandin I2 (prostacyclin) synthase 8B1 intronless; 12α-hydroxylase in bile acid synthesis pathway
CYP11 CYP11A1 CYP11B1 CYP11B2
Mitochondrial steroid hormone biosynthesis enzymes 11A1 is cholesterol side-chain cleavage enzyme, the main regulated step in steroid hormone biosynthesis. 11B1 is 11β-hydroxylase 11B2 is 18-hydroxylase
CYP17 CYP17A1 17α-hydroxylase/17-20 lyase in steroid hormone biosynthesis pathway
CYP19 CYP19A1 Aromatase CYP20 CYP20A1 Present in many species, but deviates from P450 consensus
sequence; function unknown CYP21 CYP21A2 21-hydroxylase (pseudogene nearby causes high rate of
inborn errors) CYP24 CYP24A1 24-hydroxylase for 1α-25-dihydroxyvitamin D in breakdown
pathway CYP26 CYP26A1
CYP26B1 CYP26C1
Retinoid 4-hydroxylase and 18 hydroxylase
CYP27 CYP27A1 CYP27B1 CYP27C1
27A1 hydroxylase in bile acid synthesis pathway 27B1 1α-hydroxylase of 25-hydroxyvitamin D; catalyzes regulated activation step for vitamin D 27C1 function unknown
CYP39 CYP39A1 7α-hydroxylase in bile acid synthesis pathway CYP46 CYP46A1 Cholesterol 24S-hydroxylase in brain CYP51 CYP51A1 Lanosterol 14-demethylase in cholesterol synthesis pathway Inducers and inhibitors
HN
NH
O
O OPhenobarbital
O OO
O
Bergamottin
O OO
O
Dihydroxybergamottin
OH
HO
Tamoxifen Metabolism
Additional demethylation Isomerization Sulfotransferases N- and O-glucuronide formation
ONCH3
CH3
Tamoxifen
Cytochrome P4503A4
Cytochrome P4502D6
others
ONH
CH3
N-desmethyltamoxifen
Cytochrome P4503A4
Cytochrome P4502D6
othersO
NCH3
CH3
trans-4-hydroxytamoxifen
HO
Cytochrome P4502D6
ONH
CH3
(Z)-endoxifen
HO
Cytochrome P4503A4
Cytochrome P4502D6
others
Estrogens and Related Compounds
HO17β-Estradiol
HO
OH
Diethylstilbestrol(DES)
OH
HOEquilin
O
HOEthinylestradiol
OH
O
OOH
HO
OH
Genistein
O
O
OH
O
HOCoumestrol
ON
Tamoxifen
SOH
O
ON
HO
Raloxifene
Members of the Nuclear Receptor Superfamily
Receptor Ligand Length (residues) Chromosome
Thyroid hormone-α Thyroid hormone-β (triiodothyronine)
490 456
17 3
Vitamin D (1α,25-dihydroxyvitamin D)
427 12
Retinoic acid-α Retinoic acid-β Retinoic acid-γ (all trans retinoic acid)
462 448 454
17 3
12
Retinoid-X-α Retinoid-X-β Retinoid-X-γ (9-cis-retinoic acid)
462 533 454
9 6 1
Estrogen-α Estrogen-β (estradiol)
595 530
6 14
Glucocorticoid (GR type II) (cortisol)
777 5
Mineralocorticoid (GR type I) (aldosterone)
984 4
Androgen (testosterone)
919 X
Progesterone (progesterone)
769 (A) 933 (B) 11
O
NH3
OO
I
I
I
HO
HO
OH
OH
O
O
OO
OH
HO
O
OH
O
OHHO
O
O
OH
HO
O
O
OH
O
O
Domain Structure of the Nuclear Receptors
Variable (A/B) DBD (C) D LBD (E) F
Variable Domain DNA-binding Domain (DBD)
hinge Ligand-Binding Domain (HBD)
None ?
Dimerization Dimerization
Transactivation Transactivation Transactivation
hsp90 binding
hsp90 binding
Nuclear localization
Nuclear localization
Highly Conserved Somewhat conserved
LBDVariable DBD
Features of Selected Receptor Proteins
DNA Binding Domain
Ligand- Binding Domain
Receptor Size of
variable domain
Size (amino acids)
% Identity
Size (amino acids)
% Identity
Glucocorticoid (GR Type II)
421 66 100 250 100
Mineralocorticoid (GR Type I)
603 66 94 251 57
Progesterone 567 66 90 255 55 Androgen 559 66 91 243 52
Estrogen-α 180 66 53 250 30 Thyroid hormone-β 102 67 47 225 17
Retinoic acid-α 88 66 45 265 15 Vitamin D 24 66 42 236 <15%
(from pdb ID 3DZY)
L
LL
LL
L
RNA
pdb ID 3ERD (ER LBD Dimer bound to DES and LXXLL peptide)
Overlay of pdb ID 1QKU (estradiol bound ER LBD) and 3ERT (4-hydroxytamoxifen bound ER LBD)
Nuclear Receptor Superfamily in Humans (from NURSA.org) Family Gene Name Ligand Comments NR1 NR1A1 TRα triiodothyronine Broad expression; especially CNS
NR1A2
TRβ
triiodothyronine
Broad expression; T3 resistance observed in homozygotes for mutants
NR1B1
RARα
retinoid acid
Broad expression; especially eye, kidney, uterus, testis; dysfunction: cleft palate, and schizophrenia, psychiatric abnormalities
NR1B2
RARβ
retinoid acid
Broad expression; especially brain, heart, and skeletal muscle; dysfunction: schizophrenia autism, alcoholism, ADHD, and bipolar disorder.
NR1B3
RARγ
retinoid acid
Broad expression; especially eye, kidney,
endocrine organs, heart, and skin; dysfunction: schizophrenia, psychiatric abnormalities
NR1C1
PPARα
fatty acids
Expressed in brown adipose, liver, kidney, digestive tract, and heart; dysfunction: Type II diabetes, heart disease, metabolic
disorders.
NR1C2
PPARδ
fatty acids
Expression in digestive tract and most other tissues; dysfunction: Type II diabetes and other metabolic disorders, and Alzheimer’s disease.
NR1C3
PPARγ
fatty acids
Expressed in brown adipose, and low levels in most tissues; dysfunction: breast, lung, colon, and other cancers, Type II diabetes and other metabolic disorders, and Alzheimer’s disease.
NR1D1
Rev-Erbα
orphan; heme? Broad expression; especially CNS; constitutive repressor
NR1D2
Rev-Erbβ
orphan; heme? Broad expression; especially CNS; constitutive repressor
NR1F1 RORα orphan
Broad expression, especially CNS, testis, and
skeletal muscle; constitutive activator
NR1F2 RORβ orphan Expressed in CNS; constitutive activator
NR1F3 RORγ orphan Broad expression; especially digestive tract, liver, kidney, and thymus; constitutive activator
NR1H2 LXRβ oxysterols Broad expression; especially brain, pituitary, thyroid, kidney; responsible for liver cholesterol homeostasis.
NR1H3 LXRα oxysterols Broad expression; especially gall bladder, liver, kidney, adipose tissue; dysfunction:
gallstones, altered lipid levels. Probably cholesterol sensor.
NR1H4 FXRα bile acids Expressed in digestive tract, liver, kidney (note that FXRβ is a pseudogene in humans, but is function in rodents)
NR1I1 VDR 1α, 25-dihydroxyvitamin D
Broad expression, especially in digestive tract (especially intestines), kidney, thyroid, and bone; dysfunction: bone disorders,
cancer, heart disease, immune dysfunction and autoimmune diseases, and amyotrophic lateral sclerosis, and Alzheimer’s.
NR1I2 PXR xenobiotics Expressed in digestive tract and liver; dysfunction: immune disorders (such as
inflammatory bowel disease) and cirrhosis.
NR1I3 CAR xenobiotics Expressed in digestive tract and liver.
Family Gene Name Ligand Comments NR2 NR2A1 HNF4α orphan (fatty
acids) Expressed in digestive tract and liver; dysfunction: Type II diabetes, metabolic syndrome, and kidney failure.
NR2A2 HNF4γ orphan (fatty acids)
Expressed in digestive tract and liver, and kidney.
NR2B1 RXRα 9-cis-retinoic acid Broad expression; especially liver, skeletal muscle, and skin; dysfunction: schizophrenia, psychiatric abnormalities, and immune disorders.
NR2B2 RXRβ 9-cis-retinoic acid Broad expression; especially CNS, endocrine organs, and skin; dysfunction: Type I
diabetes and other immune disorders, schizophrenia, and psychiatric abnormalities.
NR2B3 RXRγ 9-cis-retinoic acid Broad expression; especially CNS, endocrine organs, liver, heart, skeletal muscle, bone, and skin; dysfunction: Type II diabetes
disorders, schizophrenia, and psychiatric abnormalities.
NR2C1 TR2 orphan Broad expression; especially testis; acts as negative regulator of AR and ERα.
NR2C2 TR4 orphan Broad expression; especially kidney, thymus,
and testis
NR2E1 TLX orphan Expressed in cerebrum and corpus striatum; homolog of tailless.
NR2E3 PNR orphan Expressed in retina photoreceptors; dysfunction: retinitis pigmentosa.
NR2F1 COUP-TFI
orphan Broad expression; especially nervous system
NR2F2 COUP-TFII
orphan Broad expression; especially endocrine organs; involved in angiogenesis and cardiovascular development.
NR2F6 EAR2 orphan Broad expression; especially endocrine organs; involved in neuronal development, and negative regulation of renin.
Family Gene Name Ligand Comments NR3 NR3A1 ERα estradiol Broad expression; especially in pituitary,
ovary, uterus, and vas deferens; dysfunction: breast cancer, and several other cancer types, heart disease, autoimmune diseases, osteoporosis, neurodegenerative diseases (Alzheimer’s and Parkinson’s and other dementias), anorexia, ADHD, psychosis, and
reproductive defects.
NR3A2 ERβ estradiol Expressed in ovary, CNS, colon, lung, and prostate; dysfunction: breast cancer, and several other cancer types, heart disease, osteoporosis, neurodegenerative diseases (Alzheimer’s and Parkinson’s and other
dementias), anorexia, and reproductive defects.
NR3B1 ERRα orphan Broad expression; dysfunction: osteoporosis and Type II diabetes. (Note: although related to estrogen receptor, ERRα is not activated by
estradiol.
NR3B2 ERRβ orphan Broad expression, especially placenta, kidney, thyroid, testis, and heart; dysfunction: deafness. (Note: although related to estrogen receptor, ERRβ is not activated by estradiol.
NR3B3 ERRγ orphan Broad expression, especially CNS. (Note: although related to estrogen receptor, ERRγ is not activated by estradiol.
NR3C1 GR cortisol Expressed in all tissues; dysfunction: metabolic disorders, heart disease, immune
disorders, psychiatric disorders, and kidney disorders.
NR3C2 MR aldosterone cortisol
Expressed in all tissues; dysfunction: aldosterone resistance, hypertension, psychiatric disorders, and preeclampsia.
NR3C3 PR progesterone Broad expression, especially in ovary, uterus, hypothalamus, and CNS; dysfunction: cancer of breast, ovary, uterus, and prostate, osteoporosis, aneurysm, and reproductive defects.
NR3C4 AR DHT testosterone
Broad expression, especially in reproductive tract and skeletal muscle; dysfunction: cancer of prostate, ovary, colon, testis, Type I diabetes, metabolic disorders including Type II diabetes, ADHD, depression, schizophrenia, and reproductive defects.
Family Gene Name Ligand Comments NR4 NR4A1 Nur77 orphan Broad expression, especially in adrenal,
testis, lung, and skeletal muscle; involved in apoptosis and hypothalamic-pituitary axis signaling.
NR4A2 NURR1 orphan Broad expression, especially in CNS; involve in development of dopaminergic neurons and in regulation of stress responses; dysfunction:
Parkinson’s and ADHD.
NR4A3 NOR1 orphan Broad expression, especially in CNS; involved in hypothalamic-pituitary axis signaling and in regulation of stress responses.
NR5 NR5A1 SF-1 orphan Expressed in adrenal, ovary, testis, and
hypothalamus; dysfunction: decreased steroid production in adrenal, ovary, and testis, and in Type II diabetes.
NR5A2 LRH-1 orphan Expressed in digestive tract, liver, and ovary; involved in bile acid and cholesterol homeostasis.
NR6 NR6A1 GCNF orphan Broad expression at low levels, high levels in
testis; involved in embryogenesis.
NR0 NR0B1 DAX1 orphan; lacks DBD
Expressed in reproductive tissues, pituitary and hypothalamus; dysfunction is associated with hypoplasia of adrenal and gonads; acts
via inhibition of SF-1, ER, and AR DNA binding by forming heterodimers.
NR0B2 SHP orphan; lacks DBD
Expressed in adrenal, pancreas, liver, kidney, heart, lungs, and gonads; dysfunction: obesity and Type II diabetes.
Ligands
HO
1α,25-Dihydroxy-vitamin D3(Calcitriol)
OH
OHO
NH3
OO
I
I
I
HO
3,5,3´-triiodothyronine(Thyroid hormone T3)
OO9-cis-Retinoic acid
O
O
all-trans-Retinoic acid
Pioglitazone(a type of thiazolidinedione)
O NH
SO
O
NH3C
HO 24(S),25-epoxycholesterol
O
Fe2+
N
N
N
N
O
O
O
O
Iron-Protoporphyrin IX
Ligands
HO
OH
OH
O
O
H
Cholic acidHO
OHO
O
H
Deoxycholic acidHO
OHO
NH
H
Taurocholic acid
SO
OO
O
O
5β-pregnane-3,20-dioneH
O
OH
Testosterone
OH
HOEstradiol
5α-androstan-3α-olH
HO
HN
NH
O
O OPhenobarbital
NH O O
N
OH
O
N
N O
OHO
O
O
H
H
Vinblastine
Ace
tyl-
CoA
Ch
oles
tero
l
Fat
ty A
cids
β-ox
idat
ion
Bil
e ac
ids
Bil
e ac
idco
nju
gati
onan
d e
xcre
tion
Ch
oles
tero
lsy
nth
esis
Fat
ty a
cid
syn
thes
isB
ile
acid
syn
thes
is
Bil
e ac
idm
etab
olit
es
Tri
acyl
glyc
erol
s
TA
Gsy
nth
esis
Ace
tyl-
CoA
LX
R(l
imit
edef
fect
iven
ess
in h
um
an
s)
(+)
(–)
Isop
ren
oids
Lan
oste
rol
FX
RP
XR
FX
RP
XR
CA
RV
DR
(+)
7α-h
ydro
xy-
chol
este
rol
CY
P7A
1
(–)
PX
RC
AR
(–)
(–)
PP
AR
(+)
LX
R(–
)
LX
R
(–)
LX
R
(+)
(–)
FX
R
(–)
FX
R
Ligands
HO
Diethylstilbestrol(DES)
OH
HOEthinylestradiol
OH
HOEstrone
O
HOEquilin
O
HO
O
O
O
OH
O
O OH
OH
HOGenistein
Coumestrol
OH
HO
HO
OH
OH
EstriolEstradiol
OH
HO
S
O
CF3
FF
Fulvestrant
ON
Tamoxifen
SOH
O
ON
HO
Raloxifene
HO OHBisphenol A
O
OH
Testosterone
Related Documents
