differs from other malate synthases in that it lacks a large portion of the C-terminal domain and shows lower specific activity and efficiency. CLYBL is linked to the vitamin B12 metabolism pathway because it is strongly co-expressed with MUT, MMAA, and MMAB, three members of the mitochondrial B12 pathway. Furthermore, a loss of function polymorphism, that leads to a loss of the CLYBL protein, is simultaneously associated with low levels of B12 in human plasma. While the exact mechanism of CLYBL’s involvement in B12 metabolism is not well understood, it is thought to convert citramalyl-CoA into pyruvate and acetyl-CoA. Without this conversion, itaconyl-CoA, a precursor to citramalyl-CoA, builds up in the cell leads to the inactivation of vitamin B12. This inactivation inhibits the methionine cycle, which leads to reduced serine, glycine, one-carbon, and folate metabolism. Clinical significance Because the glyoxylate cycle occurs in bacteria and fungi, studying the mechanisms of malate synthase (as well as isocitrate lyase) is important for understanding human, animal, and plant pathogenesis. Studying malate synthase can shed light on the metabolic pathways that allow pathogens to survive inside a host as well as elucidate possible treatments. Many studies have been conducted on malate synthase activity in pathogens, including Mycobacterium tuberculosis, Pseudomonas aeruginosa, Brucella melitensis, and Escherichia coli. Mycobacterium tuberculosis Malate synthase and the glyoxylate pathway is especially important to M. tuberculosis, allowing long-term persistence of its infection. When cells of M. tuberculosis become phagocytosed, the bacterium upregulates genes encoding the glyoxylate shunt enzymes. Mycobacterium tuberculosis is one of the most well studied pathogens in connection to the enzyme malate synthase. The structure and kinetics of Mycobacterium tuberculosis malate synthase have been well categorized. Malate synthase is essential to Mycobacterium tuberculosis survival because it allows the bacteria to assimilate acetyl-CoA into long-chain carbohydrates and survive in harsh environments. Beyond this, malate synthase prevents toxicity from buildup of glyoxylate produced by isocitrate lyase. Downregulation of malate synthase results in reduced stress tolerance, persistence, and growth of Mycobacterium tuberculosis inside macrophages. The enzyme can be inhibited by small molecules (although inhibition is microenvironment dependent), which suggests that these may be used as new chemotherapies. Pseudomonas aeruginosa Pseudomonas aeruginosa causes severe infections in humans and is labeled as a critical threat by the World Health Organization because of its resistance to multiple therapies. The glyoxylate shunt is essential for Pseudomonas aeruginosa growth in a host organism. In 2017, McVey, et