Free energy and coupling

Cells drive many reactions by coupling them to ATP breakdown, which releases energy 1.

The free-energy change, ΔG = ΔG°′ + RT ln Q, is zero at equilibrium and grows in magnitude as concentrations depart from it 1. An ATPase is driven by the excess of ATP’s free energy of hydrolysis over its own requirement; the cardiac calcium pump SERCA has the smallest excess 2.

ATP in the cell

Inside cells, ATP hydrolysis releases about 1.5 to 1.8 times the energy it releases under standard conditions 1.

With all reactants at 1 M, ΔG°′ is −28 to −34 kJ/mol, depending on Mg2+ 1. At cellular concentrations, far below 1 M, ΔG is about −50 kJ/mol; about −70 kJ/mol was calculated for muscle of athletes recovering from exertion 1.

Daily ATP turnover

The heart and brain contain little ATP but make kilograms of it every day 23.

The adult heart contains about 0.6 g of ATP and requires about 6 kg a day 2. The brain contains about 2 g; ³¹P magnetic resonance gives its oxidative ATP synthesis as 7–8 kg a day 3. For the whole body, BioNumbers lists about 60 kg, one body weight, a day, calculated from oxygen consumption at 36 ATP per glucose 4.

NAD+, FAD and NADP+

Cells pass electrons from food to small molecules made from the B vitamins niacin and riboflavin 56.

NAD+ accepts two electrons and one proton; NAD, relatively oxidised, serves catabolism, and NADP, relatively reduced, biosynthesis 1. Succinate dehydrogenase, complex II, binds FAD covalently to a histidine and transfers electrons from succinate to ubiquinone 7. Hepatic oxidation of alcohol raises the NADH/NAD+ ratio, which stimulates fatty acid synthesis 8.

Proton-motive force

In mitochondria, electron flow to oxygen pumps protons across the inner membrane; their return turns ATP synthase, a rotary enzyme that makes ATP 97.

Electron flow through the respiratory chainInner mitochondrial membrane; cytochrome c in the intermembrane space
  1. NADH
  2. Complex I, NADH:ubiquinone oxidoreductaseFMN, Iron-sulfur clusters4 H+ out of the matrix per NADH; complex II also reduces ubiquinone
  3. Ubiquinol
  4. Complex III, cytochrome bc1 complex2 haem b, Rieske [2Fe-2S] cluster, Haem c1Q cycle: 4 H+ released outside, 2 H+ taken from the matrix per ubiquinol
  5. Reduced cytochrome c
  6. Complex IV, cytochrome c oxidaseO2, CuA, Haem a, Haem a3 and CuBPer 2 electrons: 2 H+ pumped out; 2 matrix H+ and ½ O2 form H2O
  7. Water

The mitochondrial membrane potential is about 160 mV; each pH unit adds about 60 mV to the proton-motive force 1. Bovine and human c-rings have eight subunits, so each turn moves eight protons and makes three ATP 97. The presumed ten protons pumped per NADH and six per succinate, plus one per ATP for transport, predict P/O ratios of 2.7 and 1.6, against measured 2.5 and 1.5 9.

Creatine phosphate

Muscle contains a small reserve of creatine phosphate (phosphocreatine), which rebuilds ATP in one step 10.

Creatine kinase catalyses MgADP + phosphocreatine + H+ ⇌ MgATP + creatine near equilibrium; the equilibrium constant is 100 at pH 7.0 and 1 mM Mg2+ 102. Phosphocreatine exceeds ATP only twofold in heart and fourfold in skeletal muscle, enough to maintain ATP for a few seconds 10.

Energy use by organ

At rest, a few small organs use much of the body’s energy 113.

MRI organ masses and Elia’s specific rates predicted the 1575 kcal a day measured by calorimetry in 131 healthy adults 11.

Organ or tissueMean mass, kgResting rate, kcal/kg/day 11
Heart0.31440
Kidneys0.29440
Brain1.33240
Liver1.39200
Skeletal muscle26.313
Adipose tissue19.44.5
Other tissues24.712