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The glycerol-3-phosphate shuttle is a mechanism that regenerates NAD+ from NADH, a by-product of
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
The glycerol-3-phosphate shuttle is a mechanism that regenerates NAD+ from NADH, a by-product of glycolysis
Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH ...
. The shuttle consists of the sequential activity of two proteins: GPD1 which transfers an electron pair from NADH to dihydroxyacetone phosphate (DHAP), forming glycerol-3-phosphate (G3P) and regenerating NAD+ needed to generate energy via glycolysis. The mitochondrial inner membrane protein GPD2 catalyzes the oxidation of G3P, regenerating DHAP in the cytosol and forming FADH2 in the mitochondrial matrix. In mammals, its activity in transporting reducing equivalents across the mitochondrial membrane is considered secondary to the malate-aspartate shuttle.
History
The glycerol phosphate shuttle was first characterized as a major route of mitochondrial hydride transport in the flight muscles of blow flies. It was initially believed that the system would be inactive in mammals due to the predominance of lactate dehydrogenase activity overGlycerol-3-phosphate dehydrogenase 1
Glycerol-3-phosphate dehydrogenase 1 is a protein that in humans is encoded by the GPD1 gene.
Function
This gene encodes a member of the NAD-dependent glycerol-3-phosphate dehydrogenase family. The encoded protein plays a critical role in carb ...
(GPD1) until high GPD1 and GPD2 activity were demonstrated in mammalian brown adipose tissue and pancreatic ß-islets.
Reaction
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
Flavin may refer to:
Placename
* Flavin, Aveyron, a commune in southern France
Surname
* Adrian Flavin (born 1979), a professional rugby player
* Christopher Flavin, president of the Worldwatch Institute
* Dan Flavin (1933–1996), a minimalis ...
(FAD) to FADH2. FADH2 then reduces coenzyme Q
Coenzyme Q, also known as ubiquinone and marketed as CoQ10, is a coenzyme family that is ubiquitous in animals and most bacteria (hence the name ubiquinone). In humans, the most common form is coenzyme Q10 or ubiquinone-10.
It is a 1,4-benzo ...
(ubiquinone to ubiquinol) whose electrons enter into oxidative phosphorylation
Oxidative phosphorylation (UK , US ) or electron transport-linked phosphorylation or terminal oxidation is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing chemical energy in order to produce adenosine t ...
. This reaction is irreversible.
See also
* Malate-aspartate shuttle *Mitochondrial shuttle
The mitochondrial shuttles are biochemical transport systems used to transport reducing agents across the inner mitochondrial membrane. NADH as well as NAD+ cannot cross the membrane, but it can reduce another molecule like FAD and H2that can cros ...
References
External links
* http://chemistry.elmhurst.edu/vchembook/601glycolysissum.html (describes the shuttle in the context of glycolysis) Cellular respiration {{biochemistry-stub