Question

1. Compare and contrast the point of entry for NADH-derived electrons into the electron-transport chain on the matrix side vs the cytosolic side of the inner mitochondrial membrane. Which of these entry points provides the most energy? Why?

Answer 1

Ans. Cytoplasmic NADH (from glycolysis), when transferred to mitochondria through specific carrier (say, Glycerol-3-phospate shuttle), produces only 1.5 ATP when compared to 2.5 ATP from mitochondrial NADH (from TCA cycle).

The reaction occurring at Glycerol-3-phosphate shuttle is-

NAHD (cytosol) + Enzyme-FAD (Mitochondria) <------------>

NAD⁺ (cytosol) + Enzyme-FADH₂ (mitochondria)

Note that the electron from cytosolic NADH is transferred to enzyme-bound FAD during the transport through Glycerol-3-phophate shuttle. The resultant FADH₂ is oxidized at complex II of ETC (whereas NADH is oxidized at complex I) which transports NO protons from mitochondrial matrix to intermembrane space. Therefore, oxidization of FADH₂ at complex II produces lesser amount of ATP (1.5 ATP per FADH2 compared to 2.5 ATP per NADH) because it generates lesser amount of proton gradient across the inner mitochondrial membrane.

# So, the amount of ATP derived from NDAH depends on compartmentalization in the cell and source of NADH –

I. If NADH is produced in mitochondria, say during TCA cycle, it is directly oxidized at complex I of ETC. And, it produces 2.5 ATP per NADH.

II. If NADH in produced in cytosol (say, during glycolysis) and enters mitochondria through Glycerol-3-phosphate shuttle in form of FADH₂, it would be oxidized at complex II and would produce 1.5 ATP per NADH.

III. In some cases, where no such protein is involved (for example, in prokaryotes that lack mitochondria- all processes occur in cytoplasm), cytoplasmic NADH also produces 2.5 ATP similar to matric NADH.