U01.01.083 ATP production

Aerobic metabolism, the process by which glucose is completely oxidized in the presence of oxygen, produces a significant amount of ATP. This process occurs in two main stages: Glycolysis (in the cytoplasm) and oxidative phosphorylation (in the mitochondria).

ATP Production via Aerobic Pathways

Malate-Aspartate Shuttle (Heart and Liver):
The malate-aspartate shuttle is used in heart and liver cells to transport electrons from NADH generated in glycolysis into the mitochondria. This results in the production of 32 net ATP per glucose molecule.
Glycerol-3-Phosphate Shuttle (Muscle):
The glycerol-3-phosphate shuttle, used primarily in muscle cells, transfers electrons to FADH2 instead of NADH, producing 30 net ATP per glucose molecule.

Shuttle	ATP Produced (Net)	Location
Malate-Aspartate Shuttle	32	Heart, Liver
Glycerol-3-Phosphate Shuttle	30	Muscle

Anaerobic Glycolysis

In the absence of oxygen, glucose undergoes anaerobic glycolysis, a process that results in a much lower ATP yield due to incomplete oxidation of glucose.

ATP Produced: Anaerobic glycolysis produces only 2 net ATP per glucose molecule, as it only involves the conversion of glucose to lactate without further oxidation.

Process	ATP Produced (Net)	Oxygen Requirement
Anaerobic Glycolysis	2	None

Coupling ATP Hydrolysis to Unfavorable Reactions

ATP hydrolysis (breaking down ATP into ADP and inorganic phosphate) is highly exergonic and can be coupled to drive energetically unfavorable reactions, such as active transport and biosynthesis.

Example: The sodium-potassium pump uses ATP hydrolysis to move sodium ions out of the cell and potassium ions into the cell against their concentration gradients.

Effect of Arsenic on Glycolysis

Arsenic interferes with the glycolytic pathway by inhibiting key enzymes, leading to the production of zero net ATP during glycolysis.

Impact: This toxicity prevents the usual ATP generation from glucose metabolism, leading to a severe energy deficit in affected cells.

Points to Remember:

Aerobic metabolism: Produces 30-32 ATP per glucose molecule.
Anaerobic glycolysis: Produces only 2 ATP per glucose molecule.
Shuttles: The malate-aspartate shuttle is more efficient (32 ATP) compared to the glycerol-3-phosphate shuttle (30 ATP).
ATP Hydrolysis: Can drive energetically unfavorable processes.
Arsenic: Inhibits glycolysis, leading to zero ATP production.

This summary provides key information for understanding the ATP production processes relevant for the USMLE Step 1, including the role of shuttles, anaerobic metabolism, and the toxic effect of arsenic.

USMLE Step 1 Review Series

Curriculum