Glyoxalase I (GLO1)

Glyoxalase I (GLO1) is a zinc-dependent metalloenzyme that catalyzes the first and rate-limiting step in the glyoxalase system, which detoxifies methylglyoxal and other reactive alpha-oxoaldehydes using reduced glutathione as a cofactor[1][2][5][6]. The enzyme is crucial for cellular protection against advanced glycation end-products (AGEs) and oxidative stress, maintaining cellular viability by limiting toxic glycation reactions[1][3]. Structurally, human glyoxalase I is a homodimer, each subunit binding zinc and contributing to a unique active site architecture[2][5]. GLO1 is highly expressed in many cancers and is considered an attractive therapeutic target for anticancer drugs; its inhibitors induce apoptosis in tumor cells[3][4][6]. It is also implicated in diabetic complications and neurodegenerative diseases via its regulation of methylglyoxal and glycation pathways[3]. Drugs targeting GLO1 include both inhibitors (e.g., TLSC702) and activators (e.g., resveratrol), as well as methylglyoxal scavengers (e.g., aminoguanidine)[3][4]. As a biomarker, GLO1 overexpression is associated with tumor aggressiveness; however, therapeutic intervention must account for its essential role in basic cellular defense mechanisms, raising safety and selectivity challenges when targeting this enzyme[4][7].

Other names

Lactoylglutathione lyaseGLO Iglyoxalase system enzyme I

Inhibition (by small-molecule inhibitors like TLSC702), Activation/upregulation (by activators such as resveratrol or candesartan), Scavenging of methylglyoxal (by MG scavengers)