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

• Published in: Metabolism, clinical and experimental Vol. 53; no. 1; pp. 66 - 72
• Main Authors: Michno, Anna, Skibowska, Anna, Raszeja-Specht, Anna, Ćwikowska, Justyna, Szutowicz, Andrzej
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 2004; Elsevier
• Subjects: Acetyl Coenzyme A - blood; Adult; ATP Citrate (pro-S)-Lyase - antagonists & inhibitors; ATP Citrate (pro-S)-Lyase - blood; Biological and medical sciences; Blood Glucose - analysis; Blood Platelets - physiology; Citrates - pharmacology; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 2 - blood; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enzyme Inhibitors - pharmacology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fructosamine - blood; Glycated Hemoglobin A - analysis; Humans; Lactones - pharmacology; Malondialdehyde - blood; Medical sciences; Middle Aged; Platelet Activation - drug effects; Platelet Aggregation - drug effects; Pyruvate Dehydrogenase Complex - blood; Thrombin - pharmacology; Endocrinopathy; Enzyme; Diabetes mellitus; Platelet function; Citrate; Acetyl coenzyme A; Lyases; Metabolism; ATP; Blood
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2003.07.012

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.