Table 3.

P450 7A1

Properties	References
Physiological substrates: Cholesterol, oxysterols, zimosterol, lathosterol, zymostenol, desmosterol, cholestanol, 24(S) and (R)-hydroxycholesterol, 25-hydroxycholesterol, 27-hydroxycholesterol, 20(S)-hydroxycholesterol, 7-dehydrocholesterol, cholest-4-en-3-one, bile acids (taurocholic acid, deoxycholic acid, lithocholic acid, ursodeoxycholic acid)	(Norlin, Andersson, et al. 2000; Norlin, Toll, et al. 2000; Smelt 2010; Shinkyo and Guengerich 2011; Shinkyo et al. 2011; Tempel et al. 2014; Acimovic et al. 2016; Pan et al. 2016)
Function: Cholesterol 7α-hydroxylase (Figs. 4A, 5), first step in conversion of cholesterol to bile acids
Inhibition: Causes increased cholesterol saturation of bile, enhanced liver and lower circulating LDL cholesterol content, lowering biosynthesis and excretion of bile acids
Inhibitors:
Drugs:
Cyclosporin A ^a (Sharanek et al. 2015)
Fibrates ^a (clofibrate, bezafibrate, fenofibrate, gemfibrozil) (Marrapodi and Chiang 2000; Gbaguidi and Agellon 2004; Roglans et al. 2004; Zak et al. 2007; Honda et al. 2013)
Obeticholic acid ^a (Zhang, Jackson, et al. 2017)
Natural compounds:
Guggulsterone ^b (Owsley and Chiang 2003)
Phorbol 12-myristate-13-acetate ^a (Wang et al. 1996)
Red grapefruit juice ^a (Davalos et al. 2006)
α-Tocopherol ^a (Gonzalez, Cruz, Ferrin, Lopez-Cillero, Fernandez-Rodriguez, et al. 2011)
Physiological compounds:
25-Hydroxycholesterol ^a (Taniguchi et al. 1994; Gbaguidi and Agellon 2004)
7-Oxocholesterol ^a (Norlin, Toll, et al. 2000)
Arachidonic acid ^a (Zhang, Wand, et al. 2017)
Bile acids (free and glycine conjugated) ^a (chenodeoxycholic acid, deoxycholic acid, glycoursodeoxycholic acid, glycodeoxycholic acid, glycocholic acid) (Chiang et al. 2000; Chen et al. 2001; Ellis E et al. 2003; Li T, Jahan, et al. 2006; Smelt 2010; Gonzalez, Cruz, Ferrin, Lopez-Cillero, Briceno, et al. 2011; Gonzalez, Cruz, Ferrin, Lopez-Cillero, Fernandez-Rodriguez, et al. 2011; Liu J et al. 2014)
cAMP ^a (Song KH and Chiang 2006)
Glucagon ^a (Song KH and Chiang 2006)
Insulin ^a (prolonged treatment) (Wang et al. 1996; Li T, Kong, et al. 2006)
Proinflammatory cytokines (interleukin-1β) ^a(Jahan and Chiang 2005; Li T, Jahan, et al. 2006)
Sitosterol ^c (Nguyen et al. 1998)
Thyroid hormones (triiodothyronine, T₃) ^a (Wang et al. 1996; Drover et al. 2002; Drover and Agellon 2004; Ellis EC 2006; Song Y et al. 2015)
α₁-Antitrypsin peptide ^a (Gerbod-Giannone et al. 2002)
Other compounds, including drug candidates:
WY-14643 (pirinixic acid) ^a (Marrapodi and Chiang 2000; Gbaguidi and Agellon 2004)
Induction: Causes enhanced biosynthesis of bile acids, cholesterol lowering effect, increased risk of gallstone formation
Inducers: Decrease of cholesterol levels, alteration of bile acid profiles
Drugs:
Dexamethasone ^d (Andreou and Prokipcak 1998)
NO-1666 (Ibrolipim) ^d (Li Q et al. 2010)
Rifampicin ^d (Gonzalez, Cruz, Ferrin, Lopez-Cillero, Briceno, et al. 2011)
Statins ^e (atorvastatin, pitavastatin, pravastatin, simvastatin, lactostatin) (Fan et al. 2004; Morikawa et al. 2007; Parker et al. 2013)
Natural compounds:
Dipeptides ^d (Asp-Lys, Glu-Lys, and Trp-Lys) (Norlin and Wikvall 2007)
Farnesylquinone and derivatives ^e (Liu D et al. 2014)
Fish oil ^f (Jonkers et al. 2006; Smelt 2010)
Crocin, chlorogenic acid, geniposide, and quercetin (in combination) ^d (Leng et al. 2018)
Physiological compounds:
Cholestyramine ^g (Norlin, Andersson, et al. 2000; Norlin and Wikvall 2007)
Glucose ^g (Li T et al. 2010; Li T et al. 2012)
Insulin ^d (short-term treatment) (Li T, Kong, et al. 2006; Li T et al. 2012)
Taurine ^d (Guo et al. 2017)
Thyroid hormones ^e (Lammel Lindemann et al. 2014)
Other compounds:
2,4,6-Trihydroxyacetophenone ^g (Charoenteeraboon et al. 2005)
Oleic acid anilide ^d (An et al. 2008)

Footnotes:

Reduced/suppressed mRNA and/or protein level/expression and activity

Decreased/suppressed/inhibited activity/product formation

Competitive inhibition, binding to enzyme active site

Increased transcription/mRNA/protein expression/levels /and/or catalytic activity

Up-regulation of biosynthesis, increased expression of protein

Increased bile acid synthesis and mRNA levels

Increased activity, and/or increased product formation