20alpha-hydroxysteroid dehydrogenase
Encyclopedia
In enzymology, a 20-α-hydroxysteroid dehydrogenase is an enzyme
that catalyzes
the chemical reaction
The 3 substrates
of this enzyme are 17alpha,20alpha-dihydroxypregn-4-en-3-one, NAD+
, and NADP+
, whereas its 4 products
are 17-alpha-hydroxyprogesterone, NADH
, NADPH
, and H+
.
This enzyme belongs to the family of oxidoreductase
s, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is 20alpha-hydroxysteroid:NAD(P)+ 20-oxidoreductase. Other names in common use include 20alpha-hydroxy steroid dehydrogenase, 20alpha-hydroxy steroid dehydrogenase, 20alpha-HSD, and 20alpha-HSDH. This enzyme participates in c21-steroid hormone metabolism.
20alpha-HSD has been initially described as a progesterone metabolizing enzyme of the ovary. On a functional level, ovarian 20alpha-HSD is actively involved in the control of progesterone homeostasis in pregnancy of rats and mice. While 20alpha-HSD expression and activity is downregulated in the corpus luteum of pregnancy, 24 hrs prior to parturition ovarian 20alpha-HSD activity is acutely stimulated. Accordingly, in mice with targeted deletion of the 20alpha-HSD gene, progesterone blood concentration remain high throughout pregnancy which results in a delay of 2-4 days in parturition. Indicating that expression of 20alpha-HSD activity is mandatory for the induction of parturition through reduction of progesterone blood concentration.In mice, 20alpha-HSD is also expressed in the adrenals, kidneys, brain, thymus, T cells and bone marrow. Its induction in hematopoietic cells was used as an assay for the identification of T cell derived factor interleukin-3.In addition, the enzyme reduces and inactivates 17-deoxycorticosterone, the precursor of aldosterone and corticosterone.
have been solved for this class of enzymes, with PDB
accession codes , , and .
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that catalyzes
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
the chemical reaction
Chemical reaction
A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...
- 17alpha,20alpha-dihydroxypregn-4-en-3-one + NAD(P)+
17alpha-hydroxyprogesterone + NAD(P)H + H+
The 3 substrates
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
of this enzyme are 17alpha,20alpha-dihydroxypregn-4-en-3-one, NAD+
Nicotinamide adenine dinucleotide
Nicotinamide adenine dinucleotide, abbreviated NAD, is a coenzyme found in all living cells. The compound is a dinucleotide, since it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine base and the other nicotinamide.In metabolism, NAD is involved...
, and NADP+
Nicotinamide adenine dinucleotide phosphate
Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or TPN in older notation , is a coenzyme used in anabolic reactions, such as lipid and nucleic acid synthesis, which require NADPH as a reducing agent....
, whereas its 4 products
Product (chemistry)
Product are formed during chemical reactions as reagents are consumed. Products have lower energy than the reagents and are produced during the reaction according to the second law of thermodynamics. The released energy comes from changes in chemical bonds between atoms in reagent molecules and...
are 17-alpha-hydroxyprogesterone, NADH
Nicotinamide adenine dinucleotide
Nicotinamide adenine dinucleotide, abbreviated NAD, is a coenzyme found in all living cells. The compound is a dinucleotide, since it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine base and the other nicotinamide.In metabolism, NAD is involved...
, NADPH
Nicotinamide adenine dinucleotide phosphate
Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or TPN in older notation , is a coenzyme used in anabolic reactions, such as lipid and nucleic acid synthesis, which require NADPH as a reducing agent....
, and H+
Hydrogen ion
Hydrogen ion is recommended by IUPAC as a general term for all ions of hydrogen and its isotopes.Depending on the charge of the ion, two different classes can be distinguished: positively charged ions and negatively charged ions....
.
This enzyme belongs to the family of oxidoreductase
Oxidoreductase
In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule to another...
s, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is 20alpha-hydroxysteroid:NAD(P)+ 20-oxidoreductase. Other names in common use include 20alpha-hydroxy steroid dehydrogenase, 20alpha-hydroxy steroid dehydrogenase, 20alpha-HSD, and 20alpha-HSDH. This enzyme participates in c21-steroid hormone metabolism.
20alpha-HSD has been initially described as a progesterone metabolizing enzyme of the ovary. On a functional level, ovarian 20alpha-HSD is actively involved in the control of progesterone homeostasis in pregnancy of rats and mice. While 20alpha-HSD expression and activity is downregulated in the corpus luteum of pregnancy, 24 hrs prior to parturition ovarian 20alpha-HSD activity is acutely stimulated. Accordingly, in mice with targeted deletion of the 20alpha-HSD gene, progesterone blood concentration remain high throughout pregnancy which results in a delay of 2-4 days in parturition. Indicating that expression of 20alpha-HSD activity is mandatory for the induction of parturition through reduction of progesterone blood concentration.In mice, 20alpha-HSD is also expressed in the adrenals, kidneys, brain, thymus, T cells and bone marrow. Its induction in hematopoietic cells was used as an assay for the identification of T cell derived factor interleukin-3.In addition, the enzyme reduces and inactivates 17-deoxycorticosterone, the precursor of aldosterone and corticosterone.
Structural studies
As of late 2007, 3 structuresTertiary structure
In biochemistry and molecular biology, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...
have been solved for this class of enzymes, with PDB
Protein Data Bank
The Protein Data Bank is a repository for the 3-D structural data of large biological molecules, such as proteins and nucleic acids....
accession codes , , and .
See also
- 3β(or 20α)-hydroxysteroid dehydrogenase3beta(or 20alpha)-hydroxysteroid dehydrogenaseIn enzymology, a 3-β-hydroxysteroid dehydrogenase is a putative enzyme that possesses the combined activities of the 3-β-hydroxysteroid dehydrogenase/Δ-5-4 isomerase and 20-α-hydroxysteroid dehydrogenase enzymes....