Research Article| Volume 53, ISSUE 1, P66-72, January 2004

The role of adenosine triphosphate citrate lyase in the metabolism of acetyl coenzyme a and function of blood platelets in diabetes mellitus


      Diabetes is known to increase blood platelet activity. Activities of pyruvate dehydrogenase (PDH), adenosine triphosphate (ATP)-citrate lyase (ATPCL), acetyl-coenzyme A (acetyl-CoA) content, malonyl dialdehyde (MDA), synthesis, and platelet aggregation in resting conditions and after activation with thrombin were measured in diabetic subjects and in age- and sex-matched healthy subjects. Activities of ATPCL and PDH, acetyl-CoA content, and thrombin-evoked MDA synthesis as well as platelet aggregation in diabetes were 31%, 51%, 62%, 35%, and 21%, respectively, higher than in healthy subjects. In addition, activation of diabetic platelets caused 2 times greater release of acetyl-CoA from their mitochondria than in controls. Both 1.0 mmol/L (−)hydroxycitrate and 0.1 mmol/L SB-204490 decreased acetyl-CoA content in platelet cytoplasm along with suppression of MDA synthesis and platelet aggregation. These inhibitory effects were about 2 times greater in diabetic than in control platelets. The data presented indicate that the ATPCL pathway is operative in human platelets and may be responsible for provision of about 50% of acetyl units from their mitochondrial to cytoplasmic compartment. Increased acetyl-CoA synthesis in diabetic platelets may be the cause of their excessive activity in the course of the disease. ATPCL may be a target for its specific inhibitors as factors decreasing platelet activity.
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