Differing views of the role of selenium in thioredoxin reductase

Abstract

This review covers three different chemical explanations that could account for the requirement of selenium in the form of selenocysteine in the active site of mammalian thioredoxin reductase. These views are the following: (1) the traditional view of selenocysteine as a superior nucleophile relative to cysteine, (2) the superior leaving group ability of a selenol relative to a thiol due to its significantly lower pK a and, (3) the superior ability of selenium to accept electrons (electrophilicity) relative to sulfur. We term these chemical explanations as the "chemicoenzymatic" function of selenium in an enzyme. We formally define the chemico-enzymatic function of selenium as its specific chemical property that allows a selenoenzyme to catalyze its individual reaction. However we, and others, question whether selenocysteine is chemically necessary to catalyze an enzymatic reaction since cysteine-homologs of selenocysteine-containing enzymes catalyze their specific enzymatic reactions with high catalytic efficiency. There must be a unique chemical reason for the presence of selenocysteine in enzymes that explains the biological pressure on the genome to maintain the complex selenocysteine-insertion machinery. We term this biological pressure the "chemico-biological" function of selenocysteine. We discuss evidence that this chemico-biological function is the ability of selenoenzymes to resist inactivation by irreversible oxidation. The way in which selenocysteine confers resistance to oxidation could be due to the superior ability of the oxidized form of selenocysteine (Sec-SeO 2 − , seleninic acid) to be recycled back to its parent form (Sec-SeH, selenocysteine) in comparison to the same cycling of cysteine-sulfinic acid to cysteine (Cys-SO 2 − to Cys-SH).

Selective Metabolism of Hypothiocyanous Acid by Mammalian Thioredoxin Reductase Promotes Lung Innate Immunity and Antioxidant Defense

“…Although L-TrxR functions similarly to mammalian H-TrxR to reduce Trx, it lacks many of its other features including Sec expression. Sec has been proposed to broaden the substrate reactivity of mammalian H-TrxR and help it resist oxidative inactivation (22). The high nucleophilicity of Sec predisposes it for rapid, selective reaction with HOSCN (18).…”

Redox active motifs in selenoproteins

“…The size of the ring is directly linked to its chemical reactivity because if the strain is increased, the selenenylsulfide bond is destabilized. This in turn leads to a higher redox potential (more oxidizing), which favors a reduced protein (11,12). The 14-membered ring is the most ubiquitous motif in the selenoproteome.…”

Антиоксидантна Система Респіраторного Тракту Внутрішньоклітинний Антиоксидантний Захист У Респіраторному Тракті (Частина 2)

“…Селен значительно быстрее возвращается из окисленной формы (Sec-SeO 2 -) в восстановленную (Sec-Se), чем сера (Cys-SO 2 -• Cys-SH) (рис. 2) [7,18]. Благодаря этим свойствам Sec может катали-зировать окисление тиольных групп в восстано-вительной среде цитоплазмы, где соотношение восстановленной и окисленной форм глутатиона (GSH/GSSG) составляет 30/100, а окислитель-но-восстановительный потенциал равен пример-но -230 мВ [38].…”