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Literature summary for 1.3.99.23 extracted from

  • Heidenreich, S.; Witte, N.; Weber, P.; Goehring, I.; Tolkachov, A.; von Loeffelholz, C.; Doecke, S.; Bauer, M.; Stockmann, M.; Pfeiffer, A.F.H.; Birkenfeld, A.L.; Pietzke, M.; Kempa, S.; Muenzner, M.; Schupp, M.
    Retinol saturase coordinates liver metabolism by regulating ChREBP activity (2017), Nat. Commun., 8, 384 .
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
medicine enzyme RetSat is a critical regulator of liver metabolism functioning upstream of ChREBP. Pharmacological inhibition of liver RetSat may represent a therapeutic approach for steatosis Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information mouse hepatocytes and 3T3-L1 adipocytes are depleted of RetSat by siRNA for 48 h, phenotype, detailed overview Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
endoplasmic reticulum primarily Mus musculus 5783
-
endoplasmic reticulum primarily Homo sapiens 5783
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
all-trans-13,14-dihydroretinol + FAD Mus musculus
-
all-trans-retinol + FADH2
-
?
all-trans-13,14-dihydroretinol + FAD Homo sapiens
-
all-trans-retinol + FADH2
-
?
all-trans-13,14-dihydroretinol + FAD Mus musculus C57BL/6J
-
all-trans-retinol + FADH2
-
?
all-trans-13,14-dihydroretinol + NAD+ Mus musculus
-
all-trans-retinol + NADH + H+
-
?
all-trans-13,14-dihydroretinol + NAD+ Homo sapiens
-
all-trans-retinol + NADH + H+
-
?
all-trans-13,14-dihydroretinol + NAD+ Mus musculus C57BL/6J
-
all-trans-retinol + NADH + H+
-
?
all-trans-13,14-dihydroretinol + NADP+ Mus musculus
-
all-trans-retinol + NADPH + H+
-
?
all-trans-13,14-dihydroretinol + NADP+ Homo sapiens
-
all-trans-retinol + NADPH + H+
-
?
all-trans-13,14-dihydroretinol + NADP+ Mus musculus C57BL/6J
-
all-trans-retinol + NADPH + H+
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q6NUM9
-
-
Mus musculus Q64FW2
-
-
Mus musculus C57BL/6J Q64FW2
-
-

Source Tissue

Source Tissue Comment Organism Textmining
3T3-L1 cell
-
Mus musculus
-
adipocyte
-
Mus musculus
-
adipocyte
-
Homo sapiens
-
adipose tissue
-
Mus musculus
-
adipose tissue
-
Homo sapiens
-
hepatocyte primary Mus musculus
-
kidney
-
Mus musculus
-
kidney
-
Homo sapiens
-
liver
-
Mus musculus
-
liver
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
all-trans-13,14-dihydroretinol + FAD
-
Mus musculus all-trans-retinol + FADH2
-
?
all-trans-13,14-dihydroretinol + FAD
-
Homo sapiens all-trans-retinol + FADH2
-
?
all-trans-13,14-dihydroretinol + FAD
-
Mus musculus C57BL/6J all-trans-retinol + FADH2
-
?
all-trans-13,14-dihydroretinol + NAD+
-
Mus musculus all-trans-retinol + NADH + H+
-
?
all-trans-13,14-dihydroretinol + NAD+
-
Homo sapiens all-trans-retinol + NADH + H+
-
?
all-trans-13,14-dihydroretinol + NAD+
-
Mus musculus C57BL/6J all-trans-retinol + NADH + H+
-
?
all-trans-13,14-dihydroretinol + NADP+
-
Mus musculus all-trans-retinol + NADPH + H+
-
?
all-trans-13,14-dihydroretinol + NADP+
-
Homo sapiens all-trans-retinol + NADPH + H+
-
?
all-trans-13,14-dihydroretinol + NADP+
-
Mus musculus C57BL/6J all-trans-retinol + NADPH + H+
-
?

Synonyms

Synonyms Comment Organism
retinol saturase
-
Mus musculus
retinol saturase
-
Homo sapiens
RetSat
-
Mus musculus
RetSat
-
Homo sapiens

Cofactor

Cofactor Comment Organism Structure
FAD
-
Mus musculus
FAD
-
Homo sapiens
additional information retinol saturase (RetSat) is an NADH/NADPH- or FADH-dependent oxidoreductase Mus musculus
additional information retinol saturase (RetSat) is an NADH/NADPH- or FADH-dependent oxidoreductase Homo sapiens
NAD+
-
Mus musculus
NAD+
-
Homo sapiens
NADP+
-
Mus musculus
NADP+
-
Homo sapiens

Expression

Organism Comment Expression
Homo sapiens major transcriptional regulators of RetSat expression include peroxisome proliferator-activated receptor alpha (PPARalpha) and forkhead box O1 (FoxO1) in liver, and PPARgamma in adipose tissue, where RetSat's expression is robustly induced during the differentiation of precursor cells into adipocytes up

General Information

General Information Comment Organism
malfunction liver-specific depletion of RetSat in dietary obese mice lowers hepatic and circulating TGs and normalizes hyperglycemia. Mechanistically, RetSat depletion reduces the activity of carbohydrate response element binding protein (ChREBP), a cellular hexose-phosphate sensor and inducer of lipogenesis. RetSat depletion impairs the nuclear accumulation of ChREBP. Defects upon RetSat depletion are rescued by ectopic expression of ChREBP but not by its putative enzymatic product 13,14-dihydroretinol, suggesting that RetSat affects hepatic glucose sensing independent of retinol conversion. RetSat depletion in adipocyte precursor cells impaires their adipogenic conversion in vitro, and the enzyme expression in adipose tissue is downregulated in obesity. Several glycolytic genes, including aldolase (Aldoa), phosphofructokinase, liver (Pfkl) and pyruvate kinase, liver (Pklr) are downregulated upon RetSat depletion, enzyme expression analysis Mus musculus
metabolism hepatic RETSAT correlates with obesity and steatosis in humans Homo sapiens
physiological function cellular RetSat protein localizes primarily to the endoplasmic reticulum and catalyzes the conversion of retinol to 13,14-dihydroretinol (13,14-dhretinol), a retinoid metabolite that can act as precursor for the generation of 13,14-dihydroretinoic acid. Retinol saturase coordinates liver metabolism by regulating ChREBP activity. The oxidoreductase retinol saturase (RetSat) is involved in the development of fatty liver. Hepatic RetSat expression correlates with steatosis and serum triglycerides (TGs) in humans. Major transcriptional regulators of RetSat expression include peroxisome proliferator-activated receptor alpha (PPARalpha) and forkhead box O1 (FoxO1) in liver, and PPARgamma in adipose tissue, where RetSat's expression is robustly induced during the differentiation of precursor cells into adipocytes Homo sapiens
physiological function cellular RetSat protein localizes primarily to the endoplasmic reticulum and catalyzes the conversion of retinol to 13,14-dihydroretinol (13,14-dhretinol), a retinoid metabolite that can act as precursor for the generation of 13,14-dihydroretinoic acid. Retinol saturase coordinates liver metabolism by regulating ChREBP activity. The oxidoreductase retinol saturase (RetSat) is involved in the development of fatty liver. Hepatic RetSat expression correlates with steatosis and serum triglycerides (TGs) in humans. RetSat is elevated in obese mouse liver and controls lipid metabolism Mus musculus