The concentration of malonyl-CoA, a negative regulator of fatty acid oxidation, diminishes acutely in contracting skeletal muscle. To determine how this occurs, the activity and properties of acetyl-CoA carboxylase ␤ (ACC-␤), the skeletal muscle isozyme that catalyzes malonyl-CoA formation, were examined in rat gastrocnemius-soleus muscles at rest and during contractions induced by electrical stimulation of the sciatic nerve. To avoid the problem of contamination of the muscle extract by mitochondrial carboxylases, an assay was developed in which ACC-␤ was first purified by immunoprecipitation with a monoclonal antibody. ACC-␤ was quantitatively recovered in the immunopellet and exhibited a high sensitivity to citrate (12-fold activation) and a K m for acetyl-CoA (120 M) similar to that reported for ACC-␤ purified by other means. After 5 min of contraction, ACC-␤ activity was decreased by 90% despite an apparent increase in the cytosolic concentration of citrate, a positive regulator of ACC. SDS-polyacrylamide gel electrophoresis of both homogenates and immunopellets from these muscles showed a decrease in the electrophoretic mobility of ACC, suggesting that phosphorylation could account for the decrease in ACC activity. In keeping with this notion, citrate activation of ACC purified from contracting muscle was markedly depressed. In addition, homogenization of the muscles in a buffer free of phosphatase inhibitors and containing the phosphatase activators glutamate and MgCl 2 or treatment of immunoprecipitated ACC-␤ with purified protein phosphatase 2A abolished the decreases in both ACC-␤ activity and electrophoretic mobility caused by contraction. The rapid decrease in ACC-␤ activity after the onset of contractions (50% by 20 s) and its slow restoration to initial values during recovery (60 -90 min) were paralleled temporally by reciprocal changes in the activity of the ␣2 but not the ␣1 isoform of 5-AMPactivated protein kinase (AMPK). In conclusion, the results suggest that the decrease in ACC activity during muscle contraction is caused by an increase in its phosphorylation, most probably due, at least in part, to activation of the ␣2 isoform of AMPK. They also suggest a dual mechanism for ACC regulation in muscle in which inhibition by phosphorylation takes precedence over activation by citrate. These alterations in ACC and AMPK activity, by diminishing the concentration of malonyl-CoA, could be responsible for the increase in fatty acid oxidation observed in skeletal muscle during exercise.In tissues such as liver (1) and heart (2, 3), malonyl-CoA regulates fatty acid oxidation by inhibiting carnitine palmitoyl transferase I, the enzyme that catalyzes the transfer of cytosolic long chain fatty acyl-CoA into mitochondria. Evidence has been presented that it plays a similar role in skeletal muscle (4 -7), although definitive evidence is still lacking (see "Discussion"). Malonyl-CoA is synthesized from cytosolic acetyl-CoA by a reaction catalyzed by acetyl-CoA carboxylase (ACC).1 In liver, the principal ACC ...

The number of total ankle arthroplasties (TAAs) performed annually in the United States has increased. The purpose of this study was to evaluate the in-patient demographics, complications, and readmission rates of patients after TAA at academic medical centers in the United States. The University HealthSystems Consortium administrative database was searched for patients who underwent TAA in 2007 to 2011. A descriptive analysis of demographics was performed, followed by a similar analysis of clinical benchmarks, including hospital length of stay, hospital direct cost, in-hospital mortality, and 30-day readmission rates. The study included 2340 adult patients with a mean age of 62 years (47% men and 53% women) who underwent TAA. The majority of patients were Caucasian (2073; 88.5%). Average hospital length of stay was 2.2±1.26 days. Average total direct cost for the hospital was $16,212±7000 per case, with 49.7% of patients having private insurance. In-hospital mortality was less than 1%, and overall complications were 1.4%. Complications after discharge included deep venous thrombosis (2.3%), reoperation (0.7%), and infection (3.2%). A readmission rate of 2.7% within the first 30 days from the time of discharge occurred. Total ankle arthroplasty in the United States is a relatively safe procedure with low overall complication rates. Patients who are male, have a history of community-acquired pneumonia, and have a larger number of preoperative comorbidities had a significant increased risk of developing 1 complication within 30 days of surgery.

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