enzymology Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

, 6,7-dihydropteridine reductase (, also Dihydrobiopterin reductase) is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

that

catalyzes Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

the

chemical reaction A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...

: 5,6,7,8-tetrahydropteridine + NAD(P)+

\rightleftharpoons

6,7-dihydropteridine + NAD(P)H + H⁺ The four substrates for this enzyme are a 6,7-dihydropteridine ( dihydrobiopterin), NADH,

NADPH Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NAD ...

, and H⁺ and its three products are 5,6,7,8-tetrahydropteridine ( tetrahydrobiopterin), NAD⁺, and NADP⁺ This enzyme participates in

folate biosynthesis Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...

. In the human genome, the enzyme is encoded by the

QDPR QDPR (quinoid dihydropteridine reductase) is a human gene that produces the enzyme quinoid dihydropteridine reductase. This enzyme is part of the pathway that recycles a substance called tetrahydrobiopterin, also known as BH4. Tetrahydrobiopterin ...

gene.

Nomenclature

This enzyme belongs to the family of

oxidoreductase In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule, the reductant, also called the electron donor, to another, the oxidant, also called the electron acceptor. This group of enzymes usually ut ...

s, specifically those acting on the CH-NH group of donors with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is 5,6,7,8-tetrahydropteridine:NAD(P)+ oxidoreductase. Other names in common use include 6,7-dihydropteridine:NAD(P)H oxidoreductase, DHPR, NAD(P)H:6,7-dihydropteridine oxidoreductase, NADH-dihydropteridine reductase, NADPH-dihydropteridine reductase, NADPH-specific dihydropteridine reductase, dihydropteridine (reduced nicotinamide adenine dinucleotide), reductase, dihydropteridine reductase, dihydropteridine reductase (NADH), and 5,6,7,8-tetrahydropteridine:NAD(P)H+ oxidoreductase.

Clinical significance

Dihydropteridine reductase deficiency Dihydropteridine reductase deficiency (DHPRD) is a genetic disorder affecting the tetrahydrobiopterin (BH4) synthesis pathway, inherited in the autosomal recessive pattern. It is one of the six known disorders causing tetrahydrobiopterin deficiency, ...

is a defect in the regeneration of tetrahydrobiopterin. Many patients have significant developmental delays despite therapy, develop

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...

abnormalities, and are prone to sudden death. The reason is not completely clear, but might be related to the accumulation of dihydrobiopterin and abnormal

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

folic acid Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...

. Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial

International Working Group on Neurotransmitter Related Disorders The International Working Group on Neurotransmitter Related Disorders is an international collaboration of researchers studying neurotransmitter disorders. It has created a patient registry for longitudinal studies. The group studies deficiencies i ...

(iNTD). Dihydropteridine reductase deficiency is treated with

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...

supplements, a controlled diet which is lacking in

phenylalanine Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino a ...

, well as supplementation of L-DOPA.

Nomenclature

Clinical significance

See also

References

Further reading