Abstract
Lipoic acid (LA) is an organic compound that plays a key role in cellular metabolism. It participates in a posttranslational modification (PTM) named lipoylation, an event that is highly conserved and that occurs in multimeric metabolic enzymes of very distinct microorganisms such as Plasmodium sp. and Staphylococcus aureus, including pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase (KDH). In this mini review, we revisit the recent literature regarding LA metabolism in Plasmodium sp. and Staphylococcus aureus, by covering the lipoate ligase proteins in both microorganisms, the role of lipoate ligase proteins and insights for possible inhibitors of lipoate ligases.
Highlights
Lipoic acid (LA) {6,8-dithiooctanoic acid or 5-[(3R)-dithiolan-3-yl]pentanoic acid} is an organosulfur compound (Figure 1B and Figure 1C) that has long been reported for antioxidant effects and potential therapeutic benefits in treating a variety of diseases, such as neurodegenerative diseases, diabetes, and cardiovascular conditions (Marangon et al, 1999; Amom et al, 2008; McNeilly et al, 2011; Tromba et al, 2019; Li et al, 2020; Molz et al, 2021)
Two main species are responsible for the majority of malaria cases worldwide: P. vivax represents 75% of malaria cases in the Americas, while 99.7% of estimated malaria cases in Africa were caused by P. falciparum (World Health Organization, 2021)
Lipoylation of Plasmodium proteins is an event that occurs in two different compartments of the parasite: mitochondrion and the apicoplast, a unique Apicomplexan plastid organelle that evolved from endosymbiotic events
Summary
LA {6,8-dithiooctanoic acid or 5-[(3R)-dithiolan-3-yl]pentanoic acid} is an organosulfur compound (Figure 1B and Figure 1C) that has long been reported for antioxidant effects and potential therapeutic benefits in treating a variety of diseases, such as neurodegenerative diseases, diabetes, and cardiovascular conditions (Marangon et al, 1999; Amom et al, 2008; McNeilly et al, 2011; Tromba et al, 2019; Li et al, 2020; Molz et al, 2021). In addition to its potential therapeutic effects and current use as a potential antioxidant in dietary supplementation, LA is an essential cofactor for many enzymatic reactions in key biochemical pathways. LA is known to act as a cofactor in five different enzyme complexes: the glycine cleavage system (GCS), pyruvate dehydrogenase (PDH), α-ketoglutarate dehydrogenase (KGDH), branched-chain α-keto acid dehydrogenase (BCDH), and acetoin dehydrogenase (AoDH) (Oppenheim et al, 2014). LA in the free form of lipoate is attached to the E2 lysine residues or to the H protein of the GCS. More knowledge on lipoylation has been gained (Cao et al, 2018a; Laczkovich et al, 2018; Zhang et al, 2020; Tang et al, 2021), it remains an attractive topic to better understand the metabolic consequences of dysregulated lipoylation and how LA metabolism enzymes could be explored as a potential drug target in different diseases. The disulfide bond in oxidized/reduced form provides a strong redox couple that is important for reactive oxygen species (ROS) scavenging and
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