CYP7B1 Protein - Oxysterol 7-alpha-hydroxylase

CYP7B1 Protein - Oxysterol 7-alpha-hydroxylase

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">CYP7B1 Protein — Oxysterol 7-alpha-hydroxylase</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Cytochrome P450 7B1 (Oxysterol 7-alpha-hydroxylase)</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>[CYP7B1](/genes/cyp7b1)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td><a href="https://www.uniprot.org/uniprot/O76074" target="_blank">O76074</a></td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~58 kDa (513 aa)</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Endoplasmic reticulum (membrane-bound)</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Cytochrome P450 family</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Liver, Brain, Kidney, Testis</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

CYP7B1 Protein — Oxysterol 7-alpha-hydroxylase

Introduction

Cyp7B1 Protein Oxysterol 7 Alpha Hydroxylase is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

...

CYP7B1 Protein - Oxysterol 7-alpha-hydroxylase

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">CYP7B1 Protein — Oxysterol 7-alpha-hydroxylase</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Cytochrome P450 7B1 (Oxysterol 7-alpha-hydroxylase)</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>[CYP7B1](/genes/cyp7b1)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td><a href="https://www.uniprot.org/uniprot/O76074" target="_blank">O76074</a></td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~58 kDa (513 aa)</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Endoplasmic reticulum (membrane-bound)</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Cytochrome P450 family</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Liver, Brain, Kidney, Testis</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

CYP7B1 Protein — Oxysterol 7-alpha-hydroxylase

Introduction

Cyp7B1 Protein Oxysterol 7 Alpha Hydroxylase is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

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.

Structure

Enzyme Classification

• EC Number: 1.14.14.29 (steroid 7-alpha-monooxygenase)
• Family: Cytochrome P450 family 7 subfamily B
• Structure: Membrane-bound heme protein

Structural Features

• 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

Function

Catalytic Activity

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

Metabolic Pathways

| 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 |

Tissue Distribution

• Liver: Highest expression, primary site of bile acid synthesis
• Brain: [Neurons](/entities/neurons) and glia, neurosteroid metabolism
• Kidney: Steroid hormone catabolism
• Testis: Testosterone metabolism

Role in Disease

Hereditary Spastic Paraplegia (SPG5)

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

Liver Disease

Loss of CYP7B1 function leads to:

• Impaired bile acid synthesis
• Cholestasis (bile flow obstruction)
• Fat-soluble vitamin deficiency
• Progressive liver fibrosis

Therapeutic Approaches

Current Treatments

• Symptomatic Management: Muscle relaxants, physical therapy
• Cholesterol-lowering: May reduce oxysterol burden
• Supportive Care: For spasticity and mobility

Experimental Approaches

• Gene Therapy: AAV-mediated CYP7B1 delivery
• Enzyme Replacement: Recombinant protein therapy
• Small Molecule Activators: Increase residual enzyme activity

Interactions

Metabolic Interactions

• CYP27A1: Works upstream in alternative pathway
• CYP7A1: Classic pathway enzyme
• Bile Acid Synthesis Enzymes: Downstream steps

Protein Interactions

• Cytochrome P450 Oxidoreductase: Electron donor for catalysis
• ER Membrane Proteins: Part of metabolic complex

See Also

• [CYP7B1 Gene](/genes/cyp7b1)
• [Hereditary Spastic Paraplegia](/diseases/hereditary-spastic-paraplegia)
• [SPG5](/diseases/spg5)
• [Cholesterol Metabolism](/mechanisms/cholesterol-metabolism)
• [Cytochrome P450 Family](/entities/cytochrome-p450)
• [Bile Acid Synthesis](/mechanisms/bile-acid-synthesis)

Background

The study of Cyp7B1 Protein Oxysterol 7 Alpha Hydroxylase has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

External Links

• [UniProt: O76074](https://www.uniprot.org/uniprot/O76074)
• [NCBI Protein: CYP7B1](https://www.ncbi.nlm.nih.gov/protein/NP_004375)
• [BRENDA: CYP7B1](https://www.brenda-enzymes.org/enzyme.php?ECNo=1.14.14.29)

References

[Unknown, CYP7B1: A key enzyme in cholesterol homeostasis (2013)](https://doi.org/10.1194/jlr.R034140)

[Unknown, CYP7B1 mutations and hereditary spastic paraplegia (2009)](https://doi.org/10.1093/brain/awp077)

[Unknown, Oxysterols in neurodegenerative diseases (2019)](https://doi.org/10.1016/j.neurobiolaging.2019.12.015)

[Unknown, Bile acids and neurological disorders (2019)](https://doi.org/10.1016/j.jhep.2019.04.019)