The balance sheet and the amphibolic pathway

How many ATP does one glucose give? We can only estimate, and only by assuming four things:

• The pathway runs in strict order: glycolysis, then the TCA cycle, then the ETS.
• The NADH made in glycolysis enters the mitochondria and is oxidised there.
• None of the intermediates is taken away to make other compounds.
• Only glucose is being respired.

On these assumptions, one glucose can give a net gain of 38 ATP. Glycolysis: 2 ATP + 2 NADH (= 6 ATP). Link step: 2 NADH (= 6). Krebs' cycle: 6 NADH (= 18) + 2 FADH₂ (= 4) + 2 ATP. Total: 2 + 6 + 6 + 18 + 4 + 2 = 38. This is a theoretical exercise; in a real, living cell the assumptions do not all hold, because all these pathways run at the same time and share their products.

Fermentation versus aerobic respiration: fermentation breaks glucose partly, gives a net 2 ATP, and oxidises NADH slowly. Aerobic respiration breaks it down completely, gives many more ATP, and oxidises NADH vigorously.

Glucose is the favourite fuel, but others can be used. Fats are split into glycerol (which enters as PGAL) and fatty acids (which enter as acetyl CoA). Proteins are split by proteases into amino acids; after their amino group is removed (deamination), they enter as pyruvate, as acetyl CoA, or in the Krebs' cycle.

The traffic also goes the other way: when the cell needs to build fatty acids or proteins, it withdraws these same intermediates from the pathway. Since the pathway serves both breaking down (catabolism) and building up (anabolism), it is called an amphibolic pathway.