ATP Production
The generation of adenosine triphosphate, the primary energy currency of cells, primarily through oxidative phosphorylation in mitochondria. Impaired ATP production underlies the muscle weakness, cardiomyopathy, and fatigue seen in mitochondrial diseases like Barth syndrome.
Technical Context
ATP yield per glucose: glycolysis (2 ATP + 2 NADH), pyruvate dehydrogenase (2 NADH), citric acid cycle (2 ATP + 6 NADH + 2 FADH₂), oxidative phosphorylation (~30-32 ATP from NADH and FADH₂ via ETC + ATP synthase). Total: approximately 30-32 ATP per glucose (earlier estimate of 36-38 was revised based on actual H⁺/ATP ratio). Tissues with highest ATP demand: cardiac muscle (consuming approximately 6kg ATP/day — 15-20× its own weight), skeletal muscle (during exercise), brain (approximately 20% of total body ATP consumption despite 2% body weight), and kidney (active transport of solutes). Barth syndrome cardiomyopathy results from insufficient cardiac ATP production to meet the heart's extraordinary energy demands — cardiac muscle is therefore the most severely affected tissue. Elamipretide's improvement of mitochondrial ATP production is most clinically significant in high-demand tissues.