The Effect of 5’-Methylthioadenosine/S-Adenosylhomocysteine Nucleosidase Deficiency on Vitamin-Dependent Metabolism in Escherichia coli O157:H7
Ken Cornell, Ph.D.
5'-Methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTN) is an enzyme responsible for the regulation and degradation of 5’-Deoxyadenosine (5’dAdo), 5’-Methylthioadenosine (MTA), and S-adenosylhomocysteine (SAH). Deficiency in MTN results in elevated levels of 5’dAdo, MTA, and SAH nucleoside metabolites and causes product inhibition of their respective synthetic pathways. Accumulation of 5’dAdo inhibits radical S-adenosylmethionine (SAM) dependent vitamin synthesis needed for enzymes in central carbon metabolism. Enzymes that utilize these vitamins, such as pyruvate dehydrogenase complex (PDHC), are expected to have their activity reduced in E. coli cells that have the MTN gene deleted (MTN KO cells). Activity assays of vitamin-requiring (PDHC) and vitamin independent (Alcohol dehydrogenase, lactate dehydrogenase) enzymes in central carbon metabolism were performed to understand how cellular metabolism adapts to interruption of MTN activity in E. coli 0157:H7. The results show that MTN interruption causes dramatic decreases in vitamin dependent PDHC activity, which is metabolically compensated for by an increase in alcohol dehydrogenase activity.
Brodock, Colton; Krahn, Matthew; Johnston, Caleb; and Cornell, Ken, "The Effect of 5’-Methylthioadenosine/S-Adenosylhomocysteine Nucleosidase Deficiency on Vitamin-Dependent Metabolism in Escherichia coli O157:H7" (2021). 2021 Undergraduate Research Showcase. 148.