Metabolic pathway of LDL, HDL and TG, including diseases (WP4522)

Homo sapiens

This pathway shows genetic disorders related to lipoprotein metabolism. Two plasmalipoproteins, LDL and HDL, and one plasma lipid, triglyceride (TG), play an important role in this pathway. Hydrophobic lipids and fat-soluble vitamins are normally transported to the site of their uptake by transporters called lipoproteins, and any deregulation of the plasma concentrations of these proteins can cause dyslipidemias. Disorders resulting from an enzyme deficiency are highlighted in pink. More details on the composition of the various lipoproteins in this pathway are visualised in [https://www.wikipathways.org/index.php/Pathway:WP3601]. This pathway was inspired by Chapter 43 of the book of Blau (ISBN 3642403360 (978-3642403361)).
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Authors

Ingebude , Denise Slenter , Lobke Meels , Martina Summer-Kutmon , Egon Willighagen , Irene Hemel , Friederike Ehrhart , and Finterly Hu

Cited In

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Organism

Homo sapiens

Communities

Inborn Errors of Metabolism (IEM) Pathways Rare Diseases

Annotations

Disease Ontology: familial combined hyperlipidemia Tangier disease hypobetalipoproteinemia autosomal recessive hypercholesterolemia

Pathway Ontology: altered lipoprotein metabolic pathway triacylglycerol metabolic pathway familial combined hyperlipidemia pathway disease pathway lipoprotein metabolic pathway

Participants

Label Type Compact Identifier Comment
Cholesterol Metabolite chebi:16113
Cyclic fatty acids Metabolite chebi:59238
Cholesterol Metabolite chebi:16113
Cholesterol Metabolite chebi:16113
Cholesterol Metabolite chebi:16113
VLDL Metabolite chebi:39027 Very low-density lipoprotein (VLDL) is one of the two main TG (triglyceride or triacylglycerol) carrying lipoproteins, which are spheroidal macromolecular complexes responsible for transporting lipids through plasma.
IDL Metabolite chebi:132933 Itermediate-density lipoprotein (IDL), physiologically a short lived species, containd around equimolar amounts of cholesterol and Triglycerides (TG).
LDL Metabolite chebi:39026 Low-density lipoprotein (LDL) is one of the two main cholesterol carrying lipoproteins, which are spheroidal macromolecular complexes responsible for transporting lipids through plasma.
LPL GeneProduct ensembl:ENSG00000175445
LCAT GeneProduct ensembl:ENSG00000213398 AKA Lecithin-cholesterol acyl transferase
HL GeneProduct uniprot:P11150 EC 3.1.1.3
HL GeneProduct uniprot:Q9Y5X9 EC 3.1.1.3 aka LIPC
CETP GeneProduct ensembl:ENSG00000087237
MTP GeneProduct uniprot:P55157 'Catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces. Required for the secretion of plasma lipoproteins that contain apolipoprotein B.' [https://www.uniprot.org/uniprot/P55157]
PCSK9 GeneProduct ensembl:ENSG00000169174
ABCA1 GeneProduct ensembl:ENSG00000165029
LPL GeneProduct ensembl:ENSG00000175445
MTP GeneProduct uniprot:P55157 'Catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces. Required for the secretion of plasma lipoproteins that contain apolipoprotein B.' [https://www.uniprot.org/uniprot/P55157]
LDLR Protein ensembl:ENSG00000130164
SR-B1 Protein uniprot:Q8WTV0 AKA SCARB1; Receptor for HDL, mediating selective uptake of cholesteryl ether and HDL-dependent cholesterol efflux.
LDLRAP1 Protein uniprot:Q5SW96 AKA Low density lipoprotein receptor adapter protein 1; ARH1
'Adapter protein (clathrin-associated sorting protein (CLASP)) required for efficient endocytosis of the LDL receptor (LDLR) in polarized cells such as hepatocytes and lymphocytes, but not in non-polarized cells (fibroblasts). May be required for LDL binding and internalization but not for receptor clustering in coated pits. May facilitate the endocytocis of LDLR and LDLR-LDL complexes from coated pits by stabilizing the interaction between the receptor and the structural components of the pits. May also be involved in the internalization of other LDLR family members.' [https://www.uniprot.org/uniprot/Q5SW96]
Annexin A2 Protein uniprot:H0YKN4
LDL-receptor Protein uniprot:P01130
C-II Protein uniprot:P02655 AKA Apolipoprotein C2; cofactor for lipoprotein lipase (LPL) enzyme.
Remnant receptor Protein interpro:IPR038003 'The chylomicron remnant receptor accepts apoE as a ligand. Chylomicron remnants are removed from the circulation exclusively by the liver, probably because these large complexes can penetrate the unique sinusoidal vascular space. The multifunctional, α2-macroglobulin/LDL receptor-related protein (LRP) is the chylomicron remnant receptor' [https://doi.org/10.1016/B978-1-4160-6189-2.00072-X]
B48 Protein uniprot:A8MUN2 'Apolipoprotein B(apo B) occurs in the plasma in 2 main isoforms, ApoB48 and ApoB100. ApoB48 is generated when a stop codon (UAA) is created by RNA editing. As a result of the RNA editing, ApoB48 and ApoB100 share a common N-terminal sequence, but ApoB48 lacks ApoB100's C-terminal LDL receptor binding region. In fact, ApoB48 is so called because it constitutes 48% of the sequence for ApoB100. ApoB 48 is a unique protein to chylomicrons from the small intestine. After most of the lipids in the chylomicron have been absorbed, ApoB48 returns to the liver as part of the chylomicron remnant, where it is endocytosed and degraded.' [https://en.wikipedia.org/wiki/Apolipoprotein_B]
Synthesized in small intestine.
Transcript ID: ENST00000233242.4
E Protein uniprot:P02649 AKA APo E, a ligand for receptor mediated endocytosis.
B100 Protein uniprot:P04114 'Apoprotein B100 (ApoB-100) is embedded in the outer phospholipid layer of LDL particles.' [https://en.wikipedia.org/wiki/LDL_receptor]
Synthesized in liver.
B48 Protein uniprot:A8MUN2 'Apolipoprotein B(apo B) occurs in the plasma in 2 main isoforms, ApoB48 and ApoB100. ApoB48 is generated when a stop codon (UAA) is created by RNA editing. As a result of the RNA editing, ApoB48 and ApoB100 share a common N-terminal sequence, but ApoB48 lacks ApoB100's C-terminal LDL receptor binding region. In fact, ApoB48 is so called because it constitutes 48% of the sequence for ApoB100. ApoB 48 is a unique protein to chylomicrons from the small intestine. After most of the lipids in the chylomicron have been absorbed, ApoB48 returns to the liver as part of the chylomicron remnant, where it is endocytosed and degraded.' [https://en.wikipedia.org/wiki/Apolipoprotein_B]
Synthesized in small intestine.
E Protein uniprot:P02649 AKA APo E, a ligand for receptor mediated endocytosis.
A-I Protein uniprot:P02647 AKA Apo A-I; activator of lecithin-cholesterol acyl transferase (LCAT).
A-II Protein uniprot:P02652 AKA Apolipoprotein A-II
A-I Protein uniprot:P02647 AKA Apo A-I; activator of lecithin-cholesterol acyl transferase (LCAT).
B100 Protein uniprot:P04114 'Apoprotein B100 (ApoB-100) is embedded in the outer phospholipid layer of LDL particles.' [https://en.wikipedia.org/wiki/LDL_receptor]
Synthesized in liver.
B100 Protein uniprot:P04114 'Apoprotein B100 (ApoB-100) is embedded in the outer phospholipid layer of LDL particles.' [https://en.wikipedia.org/wiki/LDL_receptor]
Synthesized in liver.
C-II Protein uniprot:P02655 AKA Apolipoprotein C2; cofactor for lipoprotein lipase (LPL) enzyme.
E Protein uniprot:P02649 AKA APo E, a ligand for receptor mediated endocytosis.
E Protein uniprot:P02649 AKA APo E, a ligand for receptor mediated endocytosis.
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References

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