K. George Thampy M.D.             ST. LOUIS UNIVERSITY  
Age-related changes in mRNA expression and activity of
    acetyl-coenzyme A carboxylase  
         
 

Acetyl-CoA carboxylase (ACC) catalyzes the rate-limiting step in the synthesis of long chain fatty acids. Since aging influences adiposity we studied the activity of ACC and its mRNA expression in livers of 4mo, 12 mo and 27 mo-old F344 rats. The activity of ACC (mU/mg protein; Unit= m mole/min) in liver homogenates from 4 mo old rats was 1.01±0.14. There was an 80% increase in activity (1.83±0.27) in 12 mo-old rats (p=0.019). However, there was a significant decline in activity to 0.46±0.06 in livers of 24 mo-old rats (p=0.0018). The total activity of ACC (per g liver) followed the above trend. The enzyme from all age-groups was purified by avidin-affinity chromatography. The purified preparation migrated as a major protein band (Mr 262,000) on SDS-polyacrylamide gels. The specific activity of the purified preparation was 1.5, 1.8, and 1.8 U/mg for 4 mo, 12 mo and 24 mo old, respectively. The alkali labile phosphate content was 5.66±0.17, 5.64±0.21 and 6.21±0±.35 mols Pi/mole subunit for 4 mo, 12 mo, and 24 mo-old, respectively. Thus the 3 preparations had similar specific activity and similar phosphate content. The age-related changes in ACC mRNA-expression, as studies by RNAse protection assay, correlated with changes in total enzyme activity. In conclusion, the observed changes in the total activity and expression of ACC mRNA are in parallel with known age-related changes in adiposity which increases throughout early life to a peak level in late mid-life (12-18 mo-old) and then declines as the animal ages further.