9.41 Selenoproteins

As mentioned earlier, selenium’s antioxidant function is not due to the mineral itself, but a result of selenoproteins. This is illustrated in the figure below, where the different colored circles represent amino acids in the crescent shaped enzyme. In most enzymes, the mineral is a cofactor that is external to the enzyme, as shown on the left. Selenoenzymes contain selenocysteine as an amino acid in the active site of the enzyme. Thus, in selenoenzymes, selenium does not serve as a cofactor, which is different than most minerals required for enzyme function.

Figure 9.411 Enzyme with a mineral cofactor versus a selenoenzyme1,2

25 human selenoproteins, containing the amino acid selenocysteine, have been identified. The following table lists these selenoproteins along with their function.

Table 9.411 The 25 Human Selenoproteins1-3

Selenoprotein Function
Glutathione peroxidase 1 (GPX1) Antioxidant enzyme
Glutathione peroxidase 2 (GPX2) Antioxidant enzyme
Glutathione peroxidase 3 (GPX3) Antioxidant enzyme
Glutathione peroxidase 4 (GPX4) Antioxidant enzyme
Glutathione peroxidase 6 (GPX6) Antioxidant enzyme
Iodothyronine 5′-deiodinase-1 (DI1) Plasma T3 production
Iodothyronine 5′-deiodinase-2 (DI2) Local T3 production
Iodothyronine 5′-deiodinase-3 (DI3) T3 degradation
Thioredoxin reductase (TR1) Antioxidant enzyme
Thioredoxin reductase (TR2) Antioxidant enzyme
Thioredoxin reductase (TR3) Antioxidant enzyme
Selenophosphate synthetase 2 (SPS2) Selenophosphate synthesis
Selenoprotein 15 (Sep15) Unknown
Selenoprotein H (SepH) Unknown
Selenoprotein I (SepI) Unknown
Selenoprotein K (SepK) Unknown
Selenoprotein M (SepM) Unknown
Selenoprotein N (SepN) Unknown
Selenoprotein O (SepO) Unknown
Selenoprotein P (SepP) Unknown
Selenoprotein R (SepR) Unknown
Selenoprotein S (SepS) Unknown
Selenoprotein T (SepT) Unknown
Selenoprotein V (SepV) Unknown
Selenoprotein W (SepW) Unknown

Hopefully from looking at the table, you see that the glutathione peroxidase enzymes and thioredoxin reductases are antioxidant enzymes. The iodothyronine 5′-deiodinases are involved in the metabolism of thyroid hormones, which will be discussed further in the iodine section. For the vast majority of the other selenoproteins, their function isn’t known, so they were named selenoprotein and given a letter. As described earlier and shown below, glutathione peroxidase converts hydrogen peroxide into water.

Figure 9.412 Antioxidant enzymes that use minerals as cofactors3

Remember that thioredoxin reductase can regenerate ascorbate from dehydroascorbate in the theorized antioxidant network (shown below).

Figure 9.413 The theorized antioxidant network4

References & Links

1. Gladyshev V, Kryukov G, Fomenko D, Hatfield D. (2004) Identification of trace element-containing proteins in genomic databases. Annu Rev Nutr 24: 579-596.

2. Beckett G, Arthur J. (2005) Selenium and endocrine systems. J Endocrinol 184(3): 455-465.

3. Stipanuk MH. (2006) Biochemical, physiological, & molecular aspects of human nutrition. St. Louis, MO: Saunders Elsevier.

4. Packer L, Weber SU, Rimbach G. (2001) Molecular aspects of alpha-tocotrienol antioxidant action and cell signalling. J Nutr 131(2): 369S-373S.