Selenoproteins Classification and Functions

Table 1 lists the selenoproteins that have been unequivocally identified in mammals, together with a summary of their main locations and known functions. Of the known glutathione peroxidases, three are tetramers and one (the phospholipid hydroperoxide-specific peroxidase) is monomeric in its quaternary structure. It appears to be this class of enzymatic activity that is critical for the action of selenoproteins in maintaining immune function, and indeed, glutathione peroxidase type I knockout mice are susceptible to viral mutation and increased viral virulence, as are selenium-deficient ones. Several other selenoproteins listed in Table 1 also have antioxidant functions and activities. Reaction of glutathione peroxidase with peroxides yields selenic or seleninic acid at the active site of the enzyme, which is recycled by glutathione.

The three thioredoxin reductases act in conjunction with the sulfur protein thioredoxin and with NADPH to bind key transcription factors to DNA. The iodothyronine deiodinases modulate the thyroid hormones, helping to ensure an optimal supply of the

Table 1 Selenoprotein description and functions

Selenoprotein

Molecular description

Function

Glutathione peroxidases (GPx)

Removal of potentially harmful peroxides and modulation of eicosanoid synthesis

Type I

Tetramer

>50% of total Se in body; acts as Se buffer/store

Type II

Tetramer

May protect the intestine

Type III

Tetramer

Found in plasma and milk; synthesized in kidney

Type IV

Monomer

Phospholipid hydroperoxide GPx; abundant in testis; resistant to Se deficiency; involved in eicosanoid metabolism

Thioredoxin reductases

Transfers protons from NADPH via bound FAD to

(types I, II, III)

thioredoxin; regulates gene expression by redox control of binding of transcription factors to DNA; needed for cell viability and proliferation; can reduce dehydroascorbate and ascorbate radical to ascorbate

Iodothyronine deiodinases

Type I acts in liver and thyroid gland to convert T4 to

(types I, II, III)

T3; the other types occur in other tissues and also help to regulate thyroid hormone levels

Selenophosphate synthetase

Synthesizes selenophospate from selenide + ATP as first step in selenocysteine synthesis during Se incorporation into selenoproteins

Sperm mitochondrial capsule

Sperm structural protein required for integrity of sperm

selenoprotein

tail and its mobility; also an antioxidant, similar to GPx IV

Prostate epithelial selenoprotein

15kDa

In epithelial cells; possibly redox function, similar to GPx IV

Selenoprotein P

Accounts for 60-80% of plasma selenoproteins; contains up to 10 selenocysteines per molecule; has a transport function; binds mercury; may protect the cardiovascular system and endothelial cells

Selenoprotein W

10kDa

Small antioxidant protein found in muscle (+ heart); its loss may account for white muscle disease of sheep

18-kDa selenoprotein (SELT)

In kidney and many other tissues; not easily depleted in Se deficiency

SELR, SELN

12.6 and 47.5 kDa, respectively

Spermatid selenoprotein

34 kDa

In sperm nuclei and in stomach; has GPx activity

There are 30-50 proteins that contain Se, as detected by 75Se-labelling in mammals, only about half of which have been investigated.

There are 30-50 proteins that contain Se, as detected by 75Se-labelling in mammals, only about half of which have been investigated.

most active member of the thyroid hormones, triiodothyronine. The different selenoprotein deiodinases are found at different sites in the body. If selenium and iodine are deficient in a human population, the thyroid deficiency is more severe (and goiters are larger) than if only iodine is lacking. This situation is endemic in some areas of central Africa, including Kivu province in the Central African Republic (formerly Zaire).

The sperm mitochondrial capsule selenoprotein has a structural as well as an enzymic role, and it is responsible for both the maintenance of motility and the structural integrity of the tail of the sperm. Both human and other mammals exhibit reduced sperm motility and increased sperm rupture under conditions of low selenium supply. A study in Glasgow, Scotland, recorded enhanced sperm motility and fertility in men who received a selenium supplement.

The precise functional roles of selenoproteins P and W are not well understood. Selenoprotein P

contains more selenium (up to 10 atoms per molecule) than any other mammalian selenoprotein, and it can form equimolar selenium-mercury complexes, thereby probably helping to detoxify mercury. It is the major selenoprotein found in plasma and may also act as a selenium transport protein and selenium reserve. Selenoprotein W is found in muscle, and its decline may help explain the molecular basis of white muscle disease in selenium-deficient sheep.

Other selenoproteins have been characterized by their molecular size but not by their functions and health significance (Table 1).

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