Showing metabocard for Cholesterol (BMDB0000067)

General function:

Secondary metabolites biosynthesis, transport and catabolism

Specific function:

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.

Gene Name:

CYP3A28

Uniprot ID:

P79102

Molecular weight:

58152.0

Reactions

General function:

Secondary metabolites biosynthesis, transport and catabolism

Specific function:

Catalyzes the isomerization of prostaglandin H2 to prostacyclin (= prostaglandin I2).

Gene Name:

PTGIS

Uniprot ID:

Q29626

Molecular weight:

56629.0

Reactions

General function:

Secondary metabolites biosynthesis, transport and catabolism

Specific function:

A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone, the precursor of most steroid hormones (PubMed:11412116). Catalyzes three sequential oxidation reactions of cholesterol, namely the hydroxylation at C22 followed with the hydroxylation at C20 to yield 20R,22R-hydroxycholesterol that is further cleaved between C20 and C22 to yield the C21-steroid pregnenolone and 4-methylpentanal (PubMed:11412116). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate and reducing the second into a water molecule. Two electrons are provided by NADPH via a two-protein mitochondrial transfer system comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin) (PubMed:11412116).

Gene Name:

CYP11A1

Uniprot ID:

P00189

Molecular weight:

60333.0

General function:

Involved in 7-dehydrocholesterol reductase activity

Specific function:

Production of cholesterol by reduction of C7-C8 double bond of 7-dehydrocholesterol (7-DHC).

Gene Name:

DHCR7

Uniprot ID:

Q5E9J5

Molecular weight:

54271.0

General function:

Involved in C-8 sterol isomerase activity

Specific function:

Not Available

Gene Name:

EBP

Uniprot ID:

Q3ZBT8

Molecular weight:

26480.0

Reactions

General function:

Signal transduction mechanisms

Specific function:

Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism, but its precise physiological role is controversial. It is apparently not required for steroid hormone biosynthesis. Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides (PubMed:1649835).

Gene Name:

TSPO

Uniprot ID:

P30535

Molecular weight:

18927.0

General function:

Involved in sequence-specific DNA binding

Specific function:

Ligand-activated transcription factor. Receptor for bile acids (BAs) such as chenodeoxycholic acid (CDCA), lithocholic acid, deoxycholic acid (DCA) and allocholic acid (ACA). Plays a essential role in BA homeostasis through the regulation of genes involved in BA synthesis, conjugation and enterohepatic circulation. Also regulates lipid and glucose homeostasis and is involved innate immune response. The FXR-RXR heterodimer binds predominantly to farnesoid X receptor response elements (FXREs) containing two inverted repeats of the consensus sequence 5'-AGGTCA-3' in which the monomers are spaced by 1 nucleotide (IR-1) but also to tandem repeat DR1 sites with lower affinity, and can be activated by either FXR or RXR-specific ligands. It is proposed that monomeric nuclear receptors such as NR5A2/LRH-1 bound to coregulatory nuclear responsive element (NRE) halfsites located in close proximity to FXREs modulate transcriptional activity. In the liver activates transcription of the corepressor NR0B2 thereby indirectly inhibiting CYP7A1 and CYP8B1 (involved in BA synthesis) implicating at least in part histone demethylase KDM1A resulting in epigenomic repression, and SLC10A1/NTCP (involved in hepatic uptake of conjugated BAs). Activates transcription of the repressor MAFG (involved in regulation of BA synthesis). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine). In the intestine activates FGF19 expression and secretion leading to hepatic CYP7A1 repression. The function also involves the coordinated induction of hepatic KLB/beta-klotho expression. Regulates transcription of liver UGT2B4 and SULT2A1 involved in BA detoxification; binding to the UGT2B4 promoter seems to imply a monomeric transactivation independent of RXRA. Modulates lipid homeostasis by activating liver NR0B2/SHP-mediated repression of SREBF1 (involved in de novo lipogenesis), expression of PLTP (involved in HDL formation), SCARB1 (involved in HDL hepatic uptake), APOE, APOC1, APOC4, PPARA (involved in beta-oxidation of fatty acids), VLDLR and SDC1 (involved in the hepatic uptake of LDL and IDL remnants), and inhibiting expression of MTTP (involved in VLDL assembly). Increases expression of APOC2 (promoting lipoprotein lipase activity implicated in triglyceride clearance). Transrepresses APOA1 involving a monomeric competition with NR2A1 for binding to a DR1 element. Also reduces triglyceride clearance by inhibiting expression of ANGPTL3 and APOC3 (both involved in inhibition of lipoprotein lipase). Involved in glucose homeostasis by modulating hepatic gluconeogenesis through activation of NR0B2/SHP-mediated repression of respective genes. Modulates glycogen synthesis (inducing phosphorylation of glycogen synthase kinase-3). Modulates glucose-stimulated insulin secretion and is involved in insulin resistance. Involved in intestinal innate immunity. Plays a role in protecting the distal small intestine against bacterial overgrowth and preservation of the epithelial barrier. Down-regulates inflammatory cytokine expression in several types of immune cells including macrophages and mononuclear cells. Mediates trans-repression of TLR4-induced cytokine expression; the function seems to require its sumoylation and prevents N-CoR nuclear receptor corepressor clearance from target genes such as IL1B and NOS2. Involved in the TLR9-mediated protective mechanism in intestinal inflammation. Plays an anti-inflammatory role in liver inflammation; proposed to inhibit proinflammatory (but not antiapoptotic) NF-kappa-B signaling.

Gene Name:

NR1H4

Uniprot ID:

Q3SZL0

Molecular weight:

55460.0

General function:

Energy production and conversion

Specific function:

Not Available

Gene Name:

DHCR24

Uniprot ID:

A6QR14

Molecular weight:

60173.0

Reactions

General function:

Cell cycle control, cell division, chromosome partitioning

Specific function:

Participates in the reverse transport of cholesterol from tissues to the liver for excretion by promoting cholesterol efflux from tissues and by acting as a cofactor for the lecithin cholesterol acyltransferase (LCAT). As part of the SPAP complex, activates spermatozoa motility.

Gene Name:

APOA1

Uniprot ID:

P15497

Molecular weight:

30276.0

General function:

Involved in high-density lipoprotein binding

Specific function:

Not Available

Gene Name:

SCARB1

Uniprot ID:

A4IFC6

Molecular weight:

56916.0

General function:

Involved in chloride channel activity

Specific function:

Not Available

Gene Name:

CFTR

Uniprot ID:

Q9TSX2

Molecular weight:

5369.0

General function:

Not Available

Specific function:

Escort protein required for cholesterol as well as lipid homeostasis. Regulates export of the SCAP/SREBF complex from the ER upon low cholesterol. Formation of a ternary complex with INSIG at high sterol concentrations leads to masking of an ER-export signal in SCAP and retention of the complex in the ER. Low sterol concentrations trigger release of INSIG, a conformational change in the SSC domain of SCAP, unmasking of the ER export signal, recruitment into COPII-coated vesicles, transport to the Golgi complex, proteolytic cleavage of SREBF in the Golgi, release of the transcription factor fragment of SREBF from the membrane, its import into the nucleus and up-regulation of LDLR, INSIG1 and the mevalonate pathway (By similarity).

Gene Name:

SCAP

Uniprot ID:

A6QM06

Molecular weight:

139701.0

General function:

Not Available

Specific function:

May be involved in the intracellular transport of sterols or other lipids. May bind cholesterol or other sterols (By similarity).

Gene Name:

STARD5

Uniprot ID:

A1A4M6

Molecular weight:

23573.0

General function:

Involved in lipoprotein metabolic process

Specific function:

Not Available

Gene Name:

APOM

Uniprot ID:

Q3ZBQ9

Molecular weight:

13027.0

General function:

Involved in cholesterol binding

Specific function:

Plays a key role in steroid hormone synthesis by enhancing the metabolism of cholesterol into pregnenolone. Mediates the transfer of cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane where it is cleaved to pregnenolone (By similarity).

Gene Name:

STAR

Uniprot ID:

Q28918

Molecular weight:

31871.0

General function:

Cell cycle control, cell division, chromosome partitioning

Specific function:

Not Available

Gene Name:

Not Available

Uniprot ID:

Q0ZCB4

Molecular weight:

27074.0

General function:

Cell cycle control, cell division, chromosome partitioning

Specific function:

Not Available

Gene Name:

APOE

Uniprot ID:

A7YWR0

Molecular weight:

36073.0

General function:

Involved in receptor activity

Specific function:

Receptor for different ligands such as phospholipids, cholesterol ester, lipoproteins, phosphatidylserine and apoptotic cells. Receptor for HDL, mediating selective uptake of cholesteryl ether and HDL-dependent cholesterol efflux. Also facilitates the flux of free and esterified cholesterol between the cell surface and apoB-containing lipoproteins and modified lipoproteins, although less efficiently than HDL. May be involved in the phagocytosis of apoptotic cells, via its phosphatidylserine binding activity.

Gene Name:

SCARB1

Uniprot ID:

O18824

Molecular weight:

57610.0

General function:

Posttranslational modification, protein turnover, chaperones

Specific function:

A scaffold protein that connects plasma membrane proteins and regulatory components, regulating their surface expression in epithelial cells apical domains. May be involved in the coordination of a diverse range of regulatory processes for ion transport and second messenger cascades. In complex with SLC9A3R1, may cluster proteins that are functionally dependent in a mutual fashion and modulate the trafficking and the activity of the associated membrane proteins. May play a role in the cellular mechanisms associated with multidrug resistance through its interaction with ABCC2 and PDZK1IP1. May potentiate the CFTR chloride channel activity. Required for normal cell-surface expression of SCARB1. Plays a role in maintaining normal plasma cholesterol levels via its effects on SCARB1. Plays a role in the normal localization and function of the chloride-anion exchanger SLC26A6 to the plasma membrane in the brush border of the proximal tubule of the kidney. May be involved in the regulation of proximal tubular Na(+)-dependent inorganic phosphate cotransport therefore playing an important role in tubule function (By similarity).

Gene Name:

PDZK1

Uniprot ID:

Q3T0X8

Molecular weight:

57175.0

General function:

Not Available

Specific function:

Not Available

Gene Name:

LIPF

Uniprot ID:

Q29458

Molecular weight:

45231.0

Reactions