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 | 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 | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
endoplasmic reticulum | primarily | Mus musculus | 5783 | - |
endoplasmic reticulum | primarily | Homo sapiens | 5783 | - |
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 | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q6NUM9 | - |
- |
Mus musculus | Q64FW2 | - |
- |
Mus musculus C57BL/6J | Q64FW2 | - |
- |
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 | 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 | Comment | Organism |
---|---|---|
retinol saturase | - |
Mus musculus |
retinol saturase | - |
Homo sapiens |
RetSat | - |
Mus musculus |
RetSat | - |
Homo sapiens |
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 |
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 | 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 |