Table 14.

P450 46A1

Properties	References
Physiological Substrates: Cholesterol, 4 βhydroxycholesterol, 24(S)-hydroxycholesterol, 7 αhydroxycholesterol, cortisol, 7-ketocholesterol, 7-dehydrocholesterol, cholestanol, desmosterol, zymostenol, zymosterol, progesterone, testosterone, lanosterol	(Mast N. et al. 2003; Mast N. et al. 2008; Liao et al. 2009; Mast N. et al. 2010; Goyal et al. 2014; Acimovic et al. 2016; Pan et al. 2016)
Other substrates:
Drugs: Diclofenac, bufuralol, phenacetin, dextromethorphan, clotrimazole
Natural compounds: 25-Hydroxyvitamin D3
Functions: Cholesterol 24S-hydroxylase, 25- and 27-hydroxylase (minor extent) (Figs. 4, 16), eliminates cholesterol from brain, metabolizes neurosteroids and drugs that can cross the blood-brain barrier, 27-hydroxylation of 7-ketocholesterol (detoxication)
Inhibition: Reduced brain cholesterol excretion
Inhibitors: (Mast N. et al. 2010)
Drugs:
Azole drugs a (ketoconazole, posaconazole, clotrimazole, voriconazole) (Mast N. et al. 2010; Shafaati et al. 2010; Mast N. et al. 2013)
(E)-Fluvoxamine, bicalutamide, dexmedetomidine b (Mast N. et al. 2012)
Tranylcypromine, thioperamide a (Mast N. et al. 2010)
Natural compounds:
Okadaic acid c (Nunes et al. 2012)
Stimulation: Increased activity potentially involved in the pathogenesis of Alzheimer’s disease (Testa et al. 2016)
Stimulators: (Mast N. et al. 2017)
Drugs:
Efavirenz (Anderson et al. 2016) Trichostatin A (Nunes et al. 2012)
Natural compounds:
L-Glutamate, L-aspartate, γ-aminobutyric acid, acetylcholine, 1α,25-dihydroxyvitamin D3d (Mast N. et al. 2017)
Other compounds:
-PD98059, U0126 e (MEK1 inhibitors) (Nunes et al. 2012)

Footnotes

^aCompetitive inhibition, ligand binding

^bCompetitive inhibition, binding to enzyme active site

^cReduced/suppressed mRNA and/or protein level/expression and activity

^dActivation/stimulation

^eIncreased transcription/mRNA/protein expression levels and/or catalytic activity