1. Mitochondrial Amino Acid Metabolism Provides Vulnerabilities in Mutant KRAS-Driven Cancers 
Yatrik M. Shah, Costas A. Lyssiotis 
Gastroenterology 
Volume 151, Issue 5, Pages (November 2016)
DOI: /j.gastro
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2. Figure 1
Anaplerotic mitochondrial amino acid metabolism. Cancer cells consume glutamine (Gln), which can be used in protein biosynthesis or biosynthetic pathways involving nitrogen capture/metabolism. Removal of nitrogen from Gln yields the amino acid glutamate (Glu). The transfer of Glu across the inner mitochondrial membrane (IMM) into the matrix enables anaplerotic tricarboxylic acid (TCA) cycle metabolism. Biosynthetic intermediates derived from Glu leave the TCA cycle and can be used in lipid and amino acid biosynthesis. An important intermediate is aspartate (Asp), which can be use in pyrimidine biosynthesis (to make DNA and RNA), asparagine (Asn) biosynthesis (which facilitates uptake of essential amino acids [EAA]), redox, and bioenergetic maintenance and protein biosynthesis. Mutant Kras expression drives Gln uptake and anaplerotic Gln metabolism, which is facilitated by enhanced SLC25A22 expression and activity.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2016 AGA Institute Terms and Conditions