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Literature summary for 1.3.1.3 extracted from

  • Mindnich, R.; Drury, J.E.; Penning, T.M.
    The effect of disease associated point mutations on 5beta-reductase (AKR1D1) enzyme function (2011), Chem. Biol. Interact., 191, 250-254.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 1.3.1.3

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of AKR1D1 enzyme mutants in HEK-293 cells only at low levels possible and with low activities Homo sapiens

Protein Variants

Protein Variants Comment Organism
G223E naturally occuring mutation, identified in patients with functional bile acid deficiency, a non-synonymous point mutations in highly conserved portions of the AKR1D1 gene Homo sapiens
L106F naturally occuring mutation, identified in patients with functional bile acid deficiency, a non-synonymous point mutations in highly conserved portions of the AKR1D1 gene Homo sapiens
P133R naturally occuring mutation, identified in patients with functional bile acid deficiency, a non-synonymous point mutations in highly conserved portions of the AKR1D1 gene. The mutant exhibits reduced Km and kcat with the bile acid intermediate DELTA4-cholesten-7alpha-ol-3-one as substrate reminiscent of uncompetitive inhibition Homo sapiens
P198L naturally occuring mutation, identified in patients with functional bile acid deficiency, a non-synonymous point mutations in highly conserved portions of the AKR1D1 gene Homo sapiens
R261C naturally occuring mutation, identified in patients with functional bile acid deficiency, a non-synonymous point mutations in highly conserved portions of the AKR1D1 gene Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
DELTA 4-cholestene-7alpha,12alpha-diol-3-one + NADPH + H+ Homo sapiens a bile acid intermediate 5beta-cholestane-7alpha,12alpha-diol-3-one + NADP+
-
 ?
DELTA4-cholesten-7alpha-ol-3-one + NADPH + H+ Homo sapiens a bile acid intermediate 5beta-cholestan-7alpha-ol-3-one + NADP+
-
 ?
additional information Homo sapiens AKR1D1 catalyzes the central 5beta-reduction step and reduces bile acid precursors such as DELTA4-cholesten-7alpha-ol-3-one and DELTA 4-cholestene-7alpha,12alpha-diol-3-one to 5beta-cholestan-7alpha-ol-3-one and 5beta-cholestane-7alpha,12alpha-diol-3-one, respectively ?
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 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
 gene AKR1D1
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
DELTA 4-cholestene-7alpha,12alpha-diol-3-one + NADPH + H+ a bile acid intermediate Homo sapiens 5beta-cholestane-7alpha,12alpha-diol-3-one + NADP+
-
 ?
DELTA4-cholesten-7alpha-ol-3-one + NADPH + H+ a bile acid intermediate Homo sapiens 5beta-cholestan-7alpha-ol-3-one + NADP+
-
 ?
additional information AKR1D1 catalyzes the central 5beta-reduction step and reduces bile acid precursors such as DELTA4-cholesten-7alpha-ol-3-one and DELTA 4-cholestene-7alpha,12alpha-diol-3-one to 5beta-cholestan-7alpha-ol-3-one and 5beta-cholestane-7alpha,12alpha-diol-3-one, respectively Homo sapiens ?
-
 ?

Synonyms

Synonyms Comment Organism
AKR1D1
-
 Homo sapiens
steroid 5beta-reductase
-
 Homo sapiens

Cofactor

Cofactor Comment Organism Structure
NADPH
-
 Homo sapiens

General Information

General Information Comment Organism
evolution the enzyme is a member of the aldo-keto reductase (AKR) family Homo sapiens
malfunction deficient 5beta-reductase activity can lead to cholestasis and neo-natal liver failure and is often lethal if it remains untreated Homo sapiens
physiological function the human enzyme, AKR1D1, plays an essential role in bile-acid biosynthesis since the 5beta-configuration is required for the emulsifying properties of bile Homo sapiens