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¹³C magnetic resonance spectroscopy detection of changes in serine isotopomers reflects changes in mitochondrial redox status.

ABSTRACT: The glycine cleavage system (GCS), the major pathway of glycine catabolism in liver, is found only in the mitochondria matrix and is regulated by the oxidized nicotinamide adenine dinucleotide (NAD(+) )/reduced nicotinamide adenine dinucleotide (NADH) ratio. In conjunction with serine hydroxymethyltransferase, glycine forms the 1 and 2 positions of serine, while the 3 position is formed exclusively by GCS. Therefore, we sought to exploit this pathway to show that quantitative measurements of serine isotopomers in liver can be used to monitor the NAD(+) /NADH ratio using (13) C NMR spectroscopy. Rat hepatocytes were treated with modulators of GCS activity followed by addition of 2-(13) C-glycine, and the changes in the proportions of newly synthesized serine isotopomers were compared to controls. Cysteamine, a competitive inhibitor of GCS, prevented formation of mitochondrial 3-(13) C-serine and 2,3-(13) C-serine isotopomers while reducing 2-(13) C-serine by 55%, demonstrating that ca. 20% of glycine-derived serine is produced in the cytosol. Glucagon, which activates GCS activity, and the mitochondrial uncoupler carbonyl cyanide-3-chlorophenylhydrazone both increased serine isotopomers, whereas rotenone, an inhibitor of complex I, had the opposite effect. These results demonstrate that (13) C magnetic resonance spectroscopy monitoring of the formation of serine isotopomers in isolated rat hepatocytes given 2-(13) C-glycine reflects the changes of mitochondrial redox status.

SUBMITTER: Johnson CB

PROVIDER: S-EPMC3311781 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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¹³C magnetic resonance spectroscopy detection of changes in serine isotopomers reflects changes in mitochondrial redox status.

Johnson C Bryce CB Tikunov Andrey P AP Lee Haakil H Wolak Justyna E JE Pediaditakis Peter P Romney Doug A DA Holmuhamedov Ekhson E Gamcsik Michael P MP Macdonald Jeffrey M JM

Magnetic resonance in medicine 20111221 3

The glycine cleavage system (GCS), the major pathway of glycine catabolism in liver, is found only in the mitochondria matrix and is regulated by the oxidized nicotinamide adenine dinucleotide (NAD(+) )/reduced nicotinamide adenine dinucleotide (NADH) ratio. In conjunction with serine hydroxymethyltransferase, glycine forms the 1 and 2 positions of serine, while the 3 position is formed exclusively by GCS. Therefore, we sought to exploit this pathway to show that quantitative measurements of ser ...[more]

PMID: 22190282

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¹³C magnetic resonance spectroscopy detection of changes in serine isotopomers reflects changes in mitochondrial redox status.

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¹³C magnetic resonance spectroscopy detection of changes in serine isotopomers reflects changes in mitochondrial redox status.

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