Selenocysteine β-Lyase: Biochemistry, Regulation and Physiological Role of the Selenocysteine Decomposition Enzyme

Abstract

The enzyme selenocysteine β-lyase (SCLY) was first isolated in 1982 from pig livers, followed by its identification in bacteria. SCLY works as a homodimer, utilizing pyridoxal 5’-phosphate as a cofactor, and catalyzing the specific decomposition of the amino acid selenocysteine into alanine and selenide. The enzyme is thought to deliver its selenide as a substrate for selenophosphate synthetases, which will ultimately be reutilized in selenoprotein synthesis. SCLY subcellular localization is unresolved, as it has been observed both in the cytosol and in the nucleus depending on the technical approach used. The highest SCLY expression and activity in mammals is found in the liver and kidneys. Disruption of the Scly gene in mice led to obesity, hyperinsulinemia, glucose intolerance, and hepatic steatosis, with SCLY being suggested as a participant in the regulation of energy metabolism in a sex-dependent manner. With the physiological role of SCLY still not fully understood, this review attempts to discuss the available literature regarding SCLY in animals and provides avenues for possible future investigation.

Selenium and Selenoproteins in Adipose Tissue Physiology and Obesity

“…Selenocysteine lyase (Scly) is also involved in intracellular Se metabolism and recirculation during selenoprotein degradation [233]. Seale et al (2019) reported that Scly −/− mice maintained at Se-deficient diet were characterized by increased body weight, hyperlipidemia, and insulin resistance, but impaired retinoid X receptor (RXR) signaling [234,235].…”

“…Selenocysteine lyase (Scly) is also involved in intracellular Se metabolism and recirculation during selenoprotein degradation [233]. Seale et al (2019) reported that Scly −/− mice maintained at Se-deficient diet were characterized by increased body weight, hyperlipidemia, and insulin resistance, but impaired retinoid X receptor (RXR) signaling [234,235]. These findings generally correspond to the earlier findings of the authors demonstrating that Se-deficiency in Scly −/− mice resulted in obesity, hyperleptinemia, insulin resistance, and reduced hepatic GPX1 and Selenos levels in parallel with decreased circulating Selenop [236].…”

Selenium and hydrogen selenide: essential micronutrient and the fourth gasotransmitter?

“…This enzyme, first isolated in 1982 [15], catalyses decomposition of selenocysteine to hydrogen selenide and alanine, utilising pyridoxal 5'-phosphate as a cofactor [15]. SCL has been found in the human liver, kidney, heart and adrenal and muscle tissue in decreasing order of specific activity [17], and can be regulated by hypoxia, oxidative stress, pro-inflammatory cytokines and glucocorticoids [18][19][20]. Intracellularly, the dietary oxidation product selenate is first reduced to selenite [21] and then to hydrogen selenide, either by thioredoxin reductase [22] or through a series of redox reactions coupled to reduced glutathione (GSH) [23].…”

The algal selenoproteomes

“…Selenium (Se) is an essential trace element for many organisms, from bacteria to humans. This micronutrient plays essential roles in redox homeostasis involved in various cellular processes and may provide numerous health bene ts such as preventing cancer and heart disease, boosting immune function, and regulating the aging process [1][2][3][4][5] . The main biological form of Se is selenocysteine, the 21st amino acid in the genetic code which is encoded by the UGA codon and then co-translationally incorporated into selenoproteins.…”