Sepiapterin reductase is an
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
that in humans is encoded by the ''SPR''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Function
Sepiapterin reductase (7,8-dihydrobiopterin:NADP
+ oxidoreductase; EC 1.1.1.153) catalyzes the NADPH-dependent reduction of various carbonyl substances, including derivatives of pteridines, and belongs to a group of enzymes called
aldo-keto reductase
The aldo-keto reductase family is a family of proteins that are subdivided into 16 categories; these include a number of related monomeric NADPH-dependent oxidoreductases, such as aldehyde reductase, aldose reductase, prostaglandin F synthase, x ...
s. SPR plays an important role in the biosynthesis of
tetrahydrobiopterin
Tetrahydrobiopterin (BH4, THB), also known as sapropterin ( INN), is a cofactor of the three aromatic amino acid hydroxylase enzymes, used in the metabolism of amino acid phenylalanine and in the biosynthesis of the neurotransmitters serotoni ...
.
Reaction
Sepiapterin reductase (SPR)
catalyzes
Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...
the
chemical reaction
A chemical reaction is a process that leads to the chemistry, chemical transformation of one set of chemical substances to another. When chemical reactions occur, the atoms are rearranged and the reaction is accompanied by an Gibbs free energy, ...
L-erythro-7,8-dihydrobiopterin + NADP+
sepiapterin + NADPH + H+
Thus, the two
substrates of this enzyme are
L-erythro-7,8-dihydrobiopterin and
NADP+, whereas its three
products
Product may refer to:
Business
* Product (business), an item that can be offered to a market to satisfy the desire or need of a customer.
* Product (project management), a deliverable or set of deliverables that contribute to a business solution
...
are
sepiapterin,
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 N ...
, and a single
hydrogen ion
A hydrogen ion is created when a hydrogen atom loses or gains an electron. A positively charged hydrogen ion (or proton) can readily combine with other particles and therefore is only seen isolated when it is in a gaseous state or a nearly particl ...
(H
+).
This enzyme belongs to the
family
Family (from ) is a Social group, group of people related either by consanguinity (by recognized birth) or Affinity (law), affinity (by marriage or other relationship). It forms the basis for social order. Ideally, families offer predictabili ...
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, to be specific, those acting on the CH-OH
group
A group is a number of persons or things that are located, gathered, or classed together.
Groups of people
* Cultural group, a group whose members share the same cultural identity
* Ethnic group, a group whose members share the same ethnic iden ...
of
donor
A donor in general is a person, organization or government which donates something voluntarily. The term is usually used to represent a form of pure altruism, but is sometimes used when the payment for a service is recognized by all parties as re ...
with
NAD+ or
NADP+ as
acceptor
Acceptor may refer to:
* Acceptor (accounting), the addressee of a bill of exchange
* In the Indian Contract Act of 1872, the acceptor is the person to whom a proposal is made, and who has communicated his or her acceptance of the said proposal
* ...
. The
systematic name
A systematic name is a name given in a systematic way to one unique group, organism, object or chemical substance, out of a specific population or collection. Systematic names are usually part of a nomenclature.
A semisystematic name or semitrivi ...
of this enzyme class is 7,8-dihydrobiopterin:NADP
+ oxidoreductase. 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 ...
.
Clinical significance
Mutations of the SPR gene may cause
sepiapterin reductase deficiency, a rare disease. The clinical phenotype can include progressive psychomotor retardation, altered tone,
seizures
A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...
,
choreoathetosis
Choreoathetosis is the occurrence of involuntary movements in a combination of chorea (irregular migrating contractions) and athetosis (twisting and writhing).
It is caused by many different diseases and agents. It is a symptom of several disease ...
, temperature instability,
hypersalivation
Hypersalivation or hypersialosis is the excessive production of saliva. It has also been defined as increased amount of saliva in the mouth, which may also be caused by decreased clearance of saliva.Medscape > HypersalivationBy Erica Brownfield. P ...
,
microcephaly
Microcephaly (from Neo-Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it m ...
, and
irritability
Irritability is the excitatory ability that living organisms have to respond to changes in their environment. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimul ...
. Patients with sepiapterin reductase deficiency also manifest
dystonia
Dystonia is a neurology, neurological Hyperkinesia, hyperkinetic Movement disorders, movement disorder in which sustained or repetitive muscle contractions occur involuntarily, resulting in twisting and repetitive movements or abnormal fixed po ...
with diurnal variation,
oculogyric crises,
tremor
A tremor is an involuntary, somewhat rhythmic muscle contraction and relaxation involving neural oscillations, oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the h ...
,
hypersomnolence
Hypersomnia is a neurological disorder of excessive time spent sleeping or excessive sleepiness. It can have many possible causes (such as seasonal affective disorder) and can cause distress and problems with functioning. In the fifth edition o ...
, oculomotor
apraxia
Apraxia is a motor disorder caused by damage to the brain (specifically the posterior parietal cortex or corpus callosum), which causes difficulty with motor planning to perform tasks or movements. The nature of the damage determines the di ...
, and
weakness
Weakness is a symptom of many different medical conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, ...
. 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 (iNTD).
References
Further reading
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External links
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{{Metabolism of vitamins, coenzymes, and cofactors
EC 1.1.1
NADPH-dependent enzymes
Enzymes of known structure