| Autor: |
Ratkevicius A; School of Medical Sciences, College of Life Sciences and Medicine, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom. a.ratkevicius@abdn.ac.uk, Carroll AM, Kilikevicius A, Venckunas T, McDermott KT, Gray SR, Wackerhage H, Lionikas A |
| Jazyk: |
angličtina |
| Zdroj: |
Physiological genomics [Physiol Genomics] 2010 Oct; Vol. 42A (2), pp. 96-102. Date of Electronic Publication: 2010 Aug 17. |
| DOI: |
10.1152/physiolgenomics.00066.2010 |
| Abstrakt: |
Citrate synthase (CS) is an enzyme of the Krebs cycle that plays a key role in mitochondrial metabolism. The aim of this study was to investigate the mechanisms underlying low activity of citrate synthase (CS) in A/J mice compared with other inbred strains of mice. Enzyme activity, protein content, and mRNA levels of CS were studied in the quadriceps muscles of A/J, BALB/cByJ, C57BL/6J, C3H/HeJ, DBA/2J, and PWD/PhJ strains of mice. Cytochrome c protein content was also measured. The results of the study indicate that A/J mice have a 50-65% reduction in CS activity compared with other strains despite similar levels of Cs mRNA and lack of differences in CS and cytochrome c protein content. CS from A/J mice also showed lower Michaelis constant (K(m)) for both acetyl CoA and oxaloacetate compared with the other strains of mice. In silico analysis of the genomic sequence identified a nonsynonymous single nucleotide polymorphism (SNP) (rs29358506, H55N) in Cs gene occurring near the site of the protein interacting with acetyl CoA. Allelic variants of the polymorphism segregated with the catalytic properties of CS enzyme among the strains. In summary, H55N polymorphism in Cs could be the underlying cause of low CS activity and its high affinity for substrates in A/J mice compared with other strains. This SNP might also play a role in resistance to obesity of A/J mice. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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