Mitochondria as energy metabolism organelles
Mitochondria are double-membrane organelles capable of changing their number and shape depending on the energy demands of the cell. In skeletal muscle cells, mitochondria are elongated with a high number of cristae; in less active cells, they are small and rounded with a moderate number of cristae. With a decrease in physical activity, the mitochondrial count decreases, while physical training causes it to increase.
The structure of a mitochondrion includes:
- The outer membrane, which is smooth and structurally similar to the plasma membrane;
- The inner membrane, which is folded and forms cristae; it is built like a lipoprotein mat with a tight entanglement of proteins and lipids, ensuring its low permeability;
- Contact sites, where the membranes touch, containing numerous enzymatic proteins, including mushroom-shaped bodies known as ATP synthases;
- The intermembrane space, containing, among other components, cytochrome c, which is involved in apoptosis;
- The matrix, which contains its own circular DNA, ribosomes, enzymes, and ions.
Endosymbiotic theory of origin
According to the endosymbiotic theory, mitochondria originated from aerobic bacteria engulfed by a larger anaerobic phagocytic cell. The additional membrane was formed as a result of phagocytosis. Evidence supporting this theory includes: their own circular DNA resembling bacterial DNA; their own ribosomes; and the ability to divide independently by budding or constriction without nuclear control.
High-energy molecules
Energy is stored in high-energy bonds. The primary molecule is ATP (adenosine triphosphate), consisting of the nitrogenous base adenine, ribose, and three phosphoric acid residues. High-energy bonds are located between the phosphate groups. During dephosphorylation, one phosphate is cleaved off and energy is released: ATP → ADP → AMP. AMP no longer contains high-energy bonds.
Another important molecule is coenzyme A (HS-CoA): when a radical attaches, it forms acyl-CoA, and when a CH₃ group attaches, it forms acetyl-CoA, the key substrate of the Krebs cycle.
Preparatory and anaerobic stages
The preparatory stage takes place in the digestive system and is completed in the small intestine. Lipases, proteases, nucleases, and glycosidases break down biopolymers into monomers: amino acids, monosaccharides, fatty acids, and nucleotides. All the released energy is dissipated as heat; ATP is not stored.
The anaerobic stage (glycolysis) takes place in the hyaloplasm. From one glucose molecule (6 carbon atoms), through 10 enzymatic reactions, 2 molecules of pyruvic acid (pyruvate, 3 carbons each) are formed. The overall yield of glycolysis is 2 ATP + 2 NADH + 2 pyruvate.
Carbohydrates are utilized for energy metabolism first; fats and especially proteins are used last because they serve structural (plastic) roles. In the absence of oxygen, pyruvate is reversibly converted into lactate (lactic acid), which explains muscle soreness during intense exercise. Excessive accumulation of lactate leads to a pathological condition known as lactic acidosis.
Aerobic stage: intermediate step and the Krebs cycle
The aerobic stage includes three steps: the intermediate step, the Krebs cycle, and oxidative phosphorylation.
At the intermediate step, pyruvate is transported into the mitochondrial matrix, during which CO₂ is cleaved off, NAD⁺ is reduced to NADH, and acetyl-CoA is formed. One glucose molecule yields 2 acetyl-CoA and 2 NADH.
The Krebs cycle takes place in the matrix. Acetyl-CoA transfers its two-carbon residue to oxaloacetate (4C), forming citrate (6C). Through a series of decarboxylation and oxidation reactions, the cycle returns to oxaloacetate. One turn of the cycle produces:
- 3 molecules of NADH;
- 1 molecule of FADH₂;
- 1 molecule of GTP (energetically equivalent to ATP);
- 2 molecules of CO₂.
There are 2 turns of the cycle per glucose molecule.
Oxidative phosphorylation and the ATP balance
The electron transport chain is located in the inner mitochondrial membrane and consists of protein complexes. NADH donates hydrogen to complex I (NADH dehydrogenase), while FADH₂ donates to complex II. Electrons are transferred along the membrane via coenzyme Q and cytochrome c to complexes III and IV; their energy is used to pump protons into the intermembrane space. At complex IV, electrons bind with oxygen to form water.
The resulting proton gradient drives ATP synthase: protons return to the matrix through the enzyme's channel, which drives the synthesis of ATP from ADP and inorganic phosphate.
Energy yield:
- 1 NADH → 3 ATP;
- 1 FADH₂ → 2 ATP;
- 1 GTP → 1 ATP.
Yield by stage per glucose molecule:
- Preparatory stage — 0 ATP;
- Glycolysis — 2 ATP + 2 NADH (6 ATP) = 8 ATP;
- Intermediate step — 2 NADH = 6 ATP;
- Krebs cycle (×2): 6 NADH (18) + 2 FADH₂ (4) + 2 GTP (2) = 24 ATP.
Total yield — 38 ATP molecules per glucose molecule. When fatty acids are oxidized, the energy yield is higher, but the organism prefers to use carbohydrates, sparing fats and proteins for structural and regulatory functions.
Key points
- Mitochondria are double-membrane organelles with their own DNA and ribosomes, which supports the endosymbiotic theory of their origin.
- Energy is stored in high-energy bonds of ATP; the key intermediate substrate is acetyl-CoA.
- Energy metabolism includes three stages: preparatory (heat), anaerobic (glycolysis), and aerobic.
- Glycolysis occurs in the hyaloplasm and yields 2 ATP, 2 NADH, and 2 pyruvic acid molecules.
- The Krebs cycle takes place in the mitochondrial matrix: 2 turns yield 6 NADH, 2 FADH₂, and 2 GTP.
- The electron transport chain creates a proton gradient used by ATP synthase to synthesize ATP.
- 1 NADH = 3 ATP, 1 FADH₂ = 2 ATP; total yield is 38 ATP per glucose molecule.
- In the absence of oxygen, pyruvate turns into lactate; pathological lactate accumulation causes lactic acidosis.