| Protein Name |
Cytochrome P450 7B1 (Oxysterol 7-alpha-hydroxylase) |
| Gene |
CYP7B1 |
| UniProt ID |
O76074 |
| Molecular Weight |
~58 kDa (513 aa) |
| Subcellular Localization |
Endoplasmic reticulum (membrane-bound) |
| Protein Family |
Cytochrome P450 family |
| Expression |
Liver, Brain, Kidney, Testis |
CYP7B1 Protein (Cytochrome P450 7B1) is a member of the cytochrome P450 enzyme family that catalyzes the 7-alpha hydroxylation of various sterols, playing a crucial role in cholesterol metabolism and bile acid synthesis [1]. This enzyme is essential for both the classic and alternative bile acid synthesis pathways.
- EC Number: 1.14.14.29 (steroid 7-alpha-monooxygenase)
- Family: Cytochrome P450 family 7 subfamily B
- Structure: Membrane-bound heme protein
- N-terminal Membrane Anchor: Transmembrane helix for ER localization
- Heme-binding Domain: Core catalytic domain containing heme iron
- Substrate-binding Pocket: Stereospecific recognition of sterol substrates
- Active Site: Catalytic center for hydroxylation reactions
CYP7B1 performs multiple hydroxylase reactions:
- Cholesterol 7-alpha-hydroxylase: Converts cholesterol to 7-alpha-hydroxycholesterol
- 25-Hydroxycholesterol 7-alpha-hydroxylase: Converts 25-HC to 7-alpha,25-diHC
- 27-Hydroxycholesterol 7-alpha-hydroxylase: Converts 27-HC to 7-alpha,27-diHC
| Pathway |
Substrate |
Product |
Significance |
| Classic bile acid synthesis |
Cholesterol |
7-alpha-hydroxycholesterol |
Primary bile acid synthesis |
| Alternative pathway |
27-Hydroxycholesterol |
7-alpha,27-dihydroxycholesterol |
Important in humans |
| Oxysterol metabolism |
25-Hydroxycholesterol |
7-alpha,25-dihydroxycholesterol |
Cholesterol homeostasis |
- Liver: Highest expression, primary site of bile acid synthesis
- Brain: Neurons and glia, neurosteroid metabolism
- Kidney: Steroid hormone catabolism
- Testis: Testosterone metabolism
CYP7B1 mutations cause SPG5 through:
- Oxysterol Accumulation: 27-Hydroxycholesterol builds to toxic levels
- Neurosteroid Deficiency: Impaired synthesis of neuroprotective steroids
- Neuronal Toxicity: Oxysterols interfere with neuronal function
- Corticospinal Tract Degeneration: Progressive loss of motor neurons
Loss of CYP7B1 function leads to:
- Impaired bile acid synthesis
- Cholestasis (bile flow obstruction)
- Fat-soluble vitamin deficiency
- Progressive liver fibrosis
- Symptomatic Management: Muscle relaxants, physical therapy
- Cholesterol-lowering: May reduce oxysterol burden
- Supportive Care: For spasticity and mobility
- Gene Therapy: AAV-mediated CYP7B1 delivery
- Enzyme Replacement: Recombinant protein therapy
- Small Molecule Activators: Increase residual enzyme activity
- CYP27A1: Works upstream in alternative pathway
- CYP7A1: Classic pathway enzyme
- Bile Acid Synthesis Enzymes: Downstream steps
- Cytochrome P450 Oxidoreductase: Electron donor for catalysis
- ER Membrane Proteins: Part of metabolic complex
-
CYP7B1: A key enzyme in cholesterol homeostasis. Journal of Lipid Research, 2013.
-
CYP7B1 mutations and hereditary spastic paraplegia. Brain, 2009.
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Oxysterols in neurodegenerative diseases. Neurobiology of Aging, 2020.
-
Bile acids and neurological disorders. Journal of Hepatology, 2019.