Cholesterol 7-alpha-hydroxylase (cytochrome P450 7A1), the rate-limiting, committed first enzyme of the classic (neutral) bile-acid biosynthesis pathway. It is a heme-thiolate cytochrome P450 monooxygenase of the endoplasmic reticulum membrane that hydroxylates cholesterol at the 7-alpha position to yield 7-alpha-hydroxycholesterol, consuming molecular oxygen and reducing equivalents supplied by NADPH via cytochrome P450 reductase. This 7-alpha-hydroxylation is the rate-controlling step that commits hepatic cholesterol to catabolism and bile-acid synthesis; the enzyme also 7-alpha-hydroxylates several oxysterols (for example 24-hydroxycholesterol and 4-beta-hydroxycholesterol) as a minor activity. CYP7A1 is expressed almost exclusively in liver, and its transcription is tightly, dynamically regulated: it is repressed by bile acids through FXR-dependent feedback and induced by conditions such as glucose and cholestyramine, allowing bile-acid output to be matched to physiological demand. Loss-of-function causes CYP7A1 deficiency, an autosomal disorder characterized by hepatic cholesterol accumulation, hypercholesterolemia and premature gallstones.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0008123 cholesterol 7-alpha-monooxygenase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core molecular function. Phylogenetic (IBA) annotation to the defining catalytic activity of CYP7A1, the cholesterol 7-alpha-hydroxylase, agreeing with experimental evidence and UniProt. Reason: This is the well-established, defining molecular function of CYP7A1 (EC 1.14.14.23), supported by direct experimental assays of the recombinant human enzyme and by UniProt. Supporting Evidence: PMID:11013305 Human CYP7A, recombinantly expressed in Escherichia coli and in simian COS cells, showed 7alpha-hydroxylase activity toward both cholesterol file:human/CYP7A1/CYP7A1-uniprot.txt Catalyzes the hydroxylation of carbon hydrogen bond at 7-alpha position of cholesterol |
| GO:0006699 bile acid biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Core biological process. CYP7A1 catalyses the committed, rate-limiting first step of the classic (neutral) bile-acid biosynthesis pathway. Reason: The 7-alpha-hydroxylation of cholesterol initiates classic bile-acid synthesis; this is the central physiological role of the enzyme, consistent across IBA, ISS, IDA and IEA evidence and with Reactome. Supporting Evidence: Reactome:R-HSA-193368 synthesis of bile acids and bile salts is initiated with the conversion of cholesterol to 7alpha-hydroxycholesterol file:human/CYP7A1/CYP7A1-uniprot.txt a rate-limiting step in cholesterol catabolism and bile acid biosynthesis |
| GO:0042632 cholesterol homeostasis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: CYP7A1, as the rate-limiting enzyme of bile-acid synthesis (the major route of cholesterol elimination), is a key contributor to whole-body cholesterol homeostasis. This is a physiological/pathway-level outcome rather than the enzyme's molecular action. Reason: Well-supported physiological role (UniProt: critical regulatory enzyme of bile acid biosynthesis and cholesterol homeostasis; loss of function causes hypercholesterolemia), but it is downstream of the catalytic activity rather than a core molecular function, so it is retained as non-core. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt critical regulatory enzyme of bile acid biosynthesis and cholesterol homeostasis Reactome:R-HSA-211976 playing an important role in maintaining cholesterol homeostasis |
| GO:0004497 monooxygenase activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Correct but general parent-level InterPro-based annotation. CYP7A1 is a cytochrome P450 monooxygenase; the more specific child term GO:0008123 is the informative core function. Reason: Accurate at the family level (cytochrome P450 monooxygenase) but subsumed by the specific cholesterol 7-alpha-monooxygenase activity; kept as a correct but redundant/general annotation. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt A cytochrome P450 monooxygenase involved in the metabolism of endogenous cholesterol |
| GO:0005506 iron ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Core-supporting cofactor function. As a heme-thiolate cytochrome P450, CYP7A1 binds the heme iron essential for its monooxygenase catalysis; the crystal structure identifies Cys444 as the axial heme-Fe ligand. Reason: CYP7A1 is a heme protein whose catalysis depends on the heme iron (axial Cys444 ligand from the crystal structure); iron binding is a valid, catalytically essential cofactor annotation. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt /ligand_part="Fe" |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Core cellular component. CYP7A1 is an ER (microsomal) membrane cytochrome P450, anchored by an N-terminal transmembrane helix (residues 4-24). Reason: Well-established microsomal/ER-membrane localization, supported by UniProt subcellular location, the N-terminal transmembrane feature, and Reactome. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane Reactome:R-HSA-192051 catalysed by CYP7A1 (cholesterol 7alpha-hydroylase) in the endoplasmic reticulum membrane |
| GO:0006699 bile acid biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Core biological process (electronic duplicate of the IBA/ISS/IDA annotations). CYP7A1 initiates the classic bile-acid biosynthesis pathway. Reason: Correct and consistent with all other evidence lines for this process. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt bile acid biosynthesis |
| GO:0006707 cholesterol catabolic process | IEA GO_REF:0000120 | ACCEPT | Summary: Core biological process. Conversion of cholesterol to bile acids is the major route of cholesterol catabolism/elimination, and CYP7A1 catalyses its rate-limiting step. Reason: UniProt explicitly describes the 7-alpha-hydroxylation as a rate-limiting step in cholesterol catabolism; correct and central. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt a rate-limiting step in cholesterol catabolism and bile acid biosynthesis |
| GO:0008123 cholesterol 7-alpha-monooxygenase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Core molecular function (electronic duplicate). Matches the RHEA:21812 / EC 1.14.14.23 reaction. Reason: Correct; identical to the experimentally supported core MF. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt Catalyzes the hydroxylation of carbon hydrogen bond at 7-alpha position of cholesterol |
| GO:0008206 bile acid metabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Correct but general (ARBA) parent of bile acid biosynthetic process. The more specific GO:0006699 is the informative annotation. Reason: True but redundant with the more specific bile acid biosynthetic process annotation; retained as a correct general term. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt bile acid biosynthesis |
| GO:0016125 sterol metabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Correct but general (ARBA) term. CYP7A1 metabolizes cholesterol (a sterol) and oxysterols; subsumed by the more specific cholesterol catabolic / bile acid biosynthetic process terms. Reason: Accurate at a high level but less informative than the specific process terms already present. Supporting Evidence: Reactome:R-HSA-211976 A number of CYPs take part in cholesterol biosynthesis and elimination |
| GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Correct but general parent-level (InterPro) term describing the P450 monooxygenase chemistry. Subsumed by the specific GO:0008123. Reason: Accurate class-level description of the catalytic mechanism (inserting one O atom, reducing the other to water using NADPH-CPR electrons) but less informative than the specific activity term. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule |
| GO:0020037 heme binding | IEA GO_REF:0000002 | ACCEPT | Summary: Core-supporting cofactor function. CYP7A1 is a heme-thiolate P450; the crystal structure (Ref.12) contains heme, with Cys444 as the axial heme-Fe ligand. Reason: Heme is the essential cofactor of this cytochrome P450 (COFACTOR heme; structural evidence); a valid, catalytically required binding annotation. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt Name=heme; Xref=ChEBI:CHEBI:30413 |
| GO:0033782 24S-hydroxycholesterol 7-alpha-hydroxylase activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Genuine minor/secondary catalytic activity (EC 1.14.14.26, RHEA:46124). Recombinant human CYP7A1 7-alpha-hydroxylates 24S-hydroxycholesterol, a brain-derived oxysterol eliminated in the liver. Reason: Experimentally demonstrated (PMID:11013305) but a secondary activity relative to the core cholesterol 7-alpha-hydroxylation; retained as non-core. Supporting Evidence: PMID:11013305 showed 7alpha-hydroxylase activity toward both cholesterol and the two isomers of 24-hydroxycholesterol, with a preference for the |
| GO:0042632 cholesterol homeostasis | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Electronic duplicate of the cholesterol homeostasis annotation; a physiological/pathway-level outcome of CYP7A1's rate-limiting role in cholesterol elimination. Reason: Correct physiological role but downstream of the molecular activity; kept as non-core, consistent with the IBA/ISS duplicates. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt critical regulatory enzyme of bile acid biosynthesis and cholesterol homeostasis |
| GO:0071333 cellular response to glucose stimulus | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: CYP7A1 transcription is induced by glucose in human hepatocytes. This is a transcriptional-response property of the gene, not a molecular function of the protein. Reason: Experimentally supported (PMID:19965590) but reflects regulation of the gene rather than the enzyme's molecular action; retained as non-core. Supporting Evidence: PMID:19965590 High glucose stimulated bile acid synthesis and induced mRNA expression of cholesterol |
| GO:0032966 negative regulation of collagen biosynthetic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred (Ensembl Compara, from rat CYP7A1 P18125) indirect phenotype-derived term. There is no evidence that CYP7A1 directly regulates collagen biosynthesis; any effect would be an indirect, systemic consequence. Reason: Automatically transferred from a rat ortholog and not reflective of a direct CYP7A1 molecular/biological function; likely an indirect downstream physiological correlate rather than a bona fide process the enzyme is involved in. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt A cytochrome P450 monooxygenase involved in the metabolism of endogenous cholesterol |
| GO:0045471 response to ethanol | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, from rat P18125) physiological response term. Plausible for a hepatic drug/lipid-metabolizing enzyme but not a core function and not directly demonstrated for human CYP7A1 here. Reason: Plausible physiological response inherited from the rat ortholog; retained as non-core pending direct human evidence rather than removed. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt A cytochrome P450 monooxygenase involved in the metabolism of endogenous cholesterol |
| GO:0045542 positive regulation of cholesterol biosynthetic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred (Ensembl Compara, from rat P18125). CYP7A1 is a cholesterol-catabolic enzyme; any positive effect on cholesterol biosynthesis would be an indirect homeostatic feedback rather than a direct function. Reason: Counterintuitive for a catabolic enzyme and inherited by automated ortholog transfer; represents an indirect homeostatic correlate, not a direct role of CYP7A1 in promoting cholesterol synthesis. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt metabolism of endogenous cholesterol |
| GO:0045717 negative regulation of fatty acid biosynthetic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred (Ensembl Compara, from rat P18125) indirect metabolic term. Not a direct molecular function of CYP7A1. Reason: Automatically transferred from a rat ortholog; likely an indirect systemic-metabolism correlate (bile-acid/lipid signaling) rather than a direct CYP7A1 activity. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt A cytochrome P450 monooxygenase involved in the metabolism of endogenous cholesterol |
| GO:0070857 regulation of bile acid biosynthetic process | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: As the rate-limiting enzyme whose expression sets the flux through bile-acid synthesis, CYP7A1 is central to regulation of the pathway. This is a pathway-regulatory role rather than the enzyme's molecular action. Reason: Supported by the enzyme's rate-limiting position and its tight transcriptional control (glucose, bile-acid/FXR feedback), but downstream of the catalytic activity; kept as non-core. Supporting Evidence: PMID:19965590 the key regulatory gene in bile acid synthesis |
| GO:0071397 cellular response to cholesterol | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CYP7A1 responds to and metabolizes cellular cholesterol/oxysterols; its transcription is part of cholesterol-driven homeostatic control. Non-core physiological response. Reason: Consistent with the enzyme's role in cholesterol homeostasis and its regulation, but a downstream response rather than the core molecular function. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt metabolism of endogenous cholesterol and its oxygenated derivatives (oxysterols) |
| GO:0006699 bile acid biosynthetic process | TAS Reactome:R-HSA-193368 | ACCEPT | Summary: Core biological process, curated by Reactome as the classic bile-acid synthesis pathway initiated by CYP7A1. Reason: Authoritative Reactome curation consistent with all other evidence. Supporting Evidence: Reactome:R-HSA-193368 synthesis of bile acids and bile salts is initiated with the conversion of cholesterol to 7alpha-hydroxycholesterol |
| GO:0016125 sterol metabolic process | TAS Reactome:R-HSA-211976 | MARK AS OVER ANNOTATED | Summary: Correct but general Reactome-curated term (CYP7A1 within the Endogenous sterols grouping). Subsumed by the specific cholesterol catabolic / bile acid biosynthetic terms. Reason: Accurate high-level term but less informative than the specific process annotations already present. Supporting Evidence: Reactome:R-HSA-211976 A number of CYPs take part in cholesterol biosynthesis and elimination |
| GO:0008123 cholesterol 7-alpha-monooxygenase activity | TAS Reactome:R-HSA-192051 | ACCEPT | Summary: Core molecular function, curated by Reactome as the CYP7A1 7-hydroxylation of cholesterol reaction. Reason: Authoritative Reactome curation of the defining reaction, consistent with experimental and UniProt evidence. Supporting Evidence: Reactome:R-HSA-192051 reaction catalysed by CYP7A1 (cholesterol 7alpha-hydroylase) in the endoplasmic reticulum membrane |
| GO:0008123 cholesterol 7-alpha-monooxygenase activity | EXP PMID:11013305 24-hydroxycholesterol is a substrate for hepatic cholesterol... | ACCEPT | Summary: Core molecular function with direct experimental support. Recombinant human CYP7A shows 7-alpha-hydroxylase activity toward cholesterol. Reason: Direct experimental (EXP) evidence for the defining catalytic activity. Supporting Evidence: PMID:11013305 Human CYP7A, recombinantly expressed in Escherichia coli and in simian COS cells, showed 7alpha-hydroxylase activity toward both cholesterol |
| GO:0008123 cholesterol 7-alpha-monooxygenase activity | EXP PMID:2384150 Molecular cloning and sequence analysis of cDNA encoding hum... | ACCEPT | Summary: Core molecular function. The human cholesterol 7-alpha-hydroxylase cDNA was cloned and characterized; UniProt attaches the EC 1.14.14.23 catalytic activity to this reference. Reason: Foundational human cloning/characterization paper for cholesterol 7-alpha-hydroxylase; UniProt cites it for CATALYTIC ACTIVITY and FUNCTION. The cached abstract is cloning-focused, so the assay is in the full text; defer to the curator. Supporting Evidence: PMID:2384150 A complete cDNA clone encoding human cholesterol 7 ... alpha-hydroxylase has been isolated file:human/CYP7A1/CYP7A1-uniprot.txt Cholesterol 7-alpha-monooxygenase |
| GO:0033782 24S-hydroxycholesterol 7-alpha-hydroxylase activity | EXP PMID:11013305 24-hydroxycholesterol is a substrate for hepatic cholesterol... | KEEP AS NON CORE | Summary: Genuine minor catalytic activity with direct experimental support (EC 1.14.14.26). Recombinant human CYP7A1 7-alpha-hydroxylates both 24-hydroxycholesterol isomers, preferring the (24S) form. Reason: Experimentally demonstrated but a secondary activity relative to the core cholesterol 7-alpha-hydroxylation; retained as non-core. Supporting Evidence: PMID:11013305 showed 7alpha-hydroxylase activity toward both cholesterol and the two isomers of 24-hydroxycholesterol, with a preference for the |
| GO:0008123 cholesterol 7-alpha-monooxygenase activity | IDA PMID:12077124 Metabolism of 4 beta -hydroxycholesterol in humans. | ACCEPT | Summary: Core molecular function with direct assay evidence. Recombinant human CYP7A1 7-alpha-hydroxylates a sterol substrate (4-beta-hydroxycholesterol, and cholesterol at a faster rate). Reason: Direct (IDA) evidence that recombinant human CYP7A1 possesses sterol 7-alpha-hydroxylase activity. Supporting Evidence: PMID:12077124 beta-hydroxycholesterol was 7 alpha-hydroxylated at a slower rate than cholesterol by recombinant human CYP7A1 |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-192051 | ACCEPT | Summary: Core cellular component, Reactome-curated ER-membrane localization of the CYP7A1 reaction. Reason: Consistent with UniProt subcellular location and the N-terminal transmembrane anchor. Supporting Evidence: Reactome:R-HSA-192051 catalysed by CYP7A1 (cholesterol 7alpha-hydroylase) in the endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-1989746 | ACCEPT | Summary: ER-membrane localization annotation attributed to the Expression of CYP7A1 Reactome event, which is actually a gene transcription/translation event. The localization itself is correct (well supported by R-HSA-192051 and UniProt). Reason: The ER-membrane location is correct and well supported by UniProt and by the companion Reactome reaction R-HSA-192051; accepted for consistency with the other ER-membrane annotations, though this particular source (an expression event) is a weaker choice of evidence for a subcellular-localization annotation. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0006699 bile acid biosynthetic process | ISS GO_REF:0000024 | ACCEPT | Summary: Core biological process (sequence-similarity transfer from rat CYP7A1 P18125), consistent with the experimental human evidence. Reason: Correct; agrees with all other evidence lines for bile-acid biosynthesis. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt bile acid biosynthesis |
| GO:0006699 bile acid biosynthetic process | IDA PMID:19965590 Glucose stimulates cholesterol 7alpha-hydroxylase gene trans... | ACCEPT | Summary: CYP7A1 is central to hepatic bile-acid synthesis; high glucose induced CYP7A1 and stimulated bile-acid synthesis in human hepatocytes. Reason: Direct experimental support for CYP7A1's involvement in bile-acid synthesis in human hepatocytes. Supporting Evidence: PMID:19965590 High glucose stimulated bile acid synthesis and induced mRNA expression of cholesterol |
| GO:0006707 cholesterol catabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: Core biological process (sequence-similarity transfer from rat P18125). Bile-acid synthesis is the major route of cholesterol catabolism. Reason: Correct; consistent with UniProt describing the 7-alpha-hydroxylation as the rate-limiting step in cholesterol catabolism. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt a rate-limiting step in cholesterol catabolism |
| GO:0008123 cholesterol 7-alpha-monooxygenase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Core molecular function (sequence-similarity transfer from rat P18125), matching the experimentally established human activity. Reason: Correct; identical to the experimentally supported core MF. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt Catalyzes the hydroxylation of carbon hydrogen bond at 7-alpha position of cholesterol |
| GO:0042632 cholesterol homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Physiological role in cholesterol homeostasis (sequence-similarity transfer from rat P18125); a downstream outcome of the enzyme's rate-limiting activity. Reason: Correct physiological role but downstream of the molecular activity; kept as non-core, consistent with the IBA/IEA duplicates. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt critical regulatory enzyme of bile acid biosynthesis and cholesterol homeostasis |
| GO:0043231 intracellular membrane-bounded organelle | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Very general cellular-component term (sequence-similarity transfer). The specific and well-supported localization is the endoplasmic reticulum membrane. Reason: Correct but uninformatively general; subsumed by the ER-membrane annotation. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0070857 regulation of bile acid biosynthetic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Pathway-regulatory role (sequence-similarity transfer from rat P18125), reflecting CYP7A1's rate-limiting, tightly controlled position in bile-acid synthesis. Reason: Supported by the enzyme's rate-limiting position and transcriptional control, but downstream of the catalytic activity; non-core. Supporting Evidence: PMID:19965590 the key regulatory gene in bile acid synthesis |
| GO:0070857 regulation of bile acid biosynthetic process | IDA PMID:19965590 Glucose stimulates cholesterol 7alpha-hydroxylase gene trans... | KEEP AS NON CORE | Summary: CYP7A1 is the key regulatory gene of bile-acid synthesis; its glucose-inducible transcription controls pathway flux. Pathway-regulatory role rather than a molecular function. Reason: Experimentally anchored (PMID:19965590) but reflects rate-limiting/regulatory control of the pathway rather than the enzyme's molecular action; non-core. Supporting Evidence: PMID:19965590 the key regulatory gene in bile acid synthesis |
| GO:0071333 cellular response to glucose stimulus | IDA PMID:19965590 Glucose stimulates cholesterol 7alpha-hydroxylase gene trans... | KEEP AS NON CORE | Summary: CYP7A1 transcription is induced by high glucose in human hepatocytes via an HNF4alpha-dependent, AMPK-modulated mechanism. Transcriptional response of the gene, not a molecular function of the protein. Reason: Directly demonstrated gene-level response to glucose, but a regulatory response rather than a core function; non-core. Supporting Evidence: PMID:19965590 High glucose stimulated bile acid synthesis and induced mRNA expression of cholesterol |
| GO:0071397 cellular response to cholesterol | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CYP7A1 responds to and metabolizes cellular cholesterol/oxysterols (sequence-similarity transfer from rat P18125); a downstream homeostatic response. Reason: Consistent with the enzyme's role in cholesterol homeostasis and its feedback regulation, but a downstream response rather than the core molecular function. Supporting Evidence: file:human/CYP7A1/CYP7A1-uniprot.txt metabolism of endogenous cholesterol and its oxygenated derivatives (oxysterols) |
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Download this section (compressed HTML)Q: Beyond transcriptional feedback (FXR/bile acids, HNF4alpha, glucose), is human CYP7A1 activity subject to significant post-translational or allosteric regulation?
Q: What is the quantitative in vivo contribution of CYP7A1's oxysterol 7-alpha-hydroxylase activities (24S-hydroxycholesterol, 4-beta-hydroxycholesterol, 7-dehydrocholesterol oxidation) relative to its cholesterol 7-alpha-hydroxylation?
Experiment: Reconstitute purified recombinant human CYP7A1 with cytochrome P450 reductase and measure steady-state kinetics across cholesterol and the physiological oxysterol substrates to rank in vivo relevance.
Experiment: Use isotope-labeled flux analysis in primary human hepatocytes (or CYP7A1-edited lines) to quantify the fraction of cholesterol catabolism proceeding through the CYP7A1-initiated classic pathway versus the acidic (CYP27A1/CYP7B1) pathway.
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