Glycerol phosphate shuttle

The glycerol-3-phosphate shuttle is a mechanism used in skeletal muscle and the brain[1] that regenerates NAD+ from NADH, a by-product of glycolysis.

Cytoplasmic glycerol-3-phosphate dehydrogenase (cGPD) transfers an electron pair from NADH to dihydroxyacetone phosphate (DHAP), forming glycerol-3-phosphate (G3P) and regenerating the NAD+ needed to generate energy via glycolysis.

[4] In mammals, its activity in transporting reducing equivalents across the mitochondrial membrane is secondary to the malate–aspartate shuttle.

The glycerol phosphate shuttle was first characterized as a major route of mitochondrial hydride transport in the flight muscles of blow flies.

[8][9][10][11] In this shuttle, the enzyme called cytoplasmic glycerol-3-phosphate dehydrogenase 1 (GPD1 or cGPD) converts dihydroxyacetone phosphate (2) to glycerol 3-phosphate (1) by oxidizing one molecule of NADH to NAD+ as in the following reaction: Glycerol-3-phosphate is converted back to dihydroxyacetone phosphate by an inner membrane-bound mitochondrial glycerol-3-phosphate dehydrogenase 2 (GPD2 or mGPD), this time reducing one molecule of enzyme-bound flavin adenine dinucleotide (FAD) to FADH2.