Some of the Most Important NAD+ Linked Dehydrogenase Enzymes of The Living System
Some of the most important NAD Linked dehydrogenase enzymes are glycerol-3-phosphate dehydrogenase, Lactate dehydrogenase, alcohol and aldehyde dehydrogenase, pyruvate dehydrogenase complex, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrohgenase and glutamate dehydrogenase.
Glyceraldehyde-3-Phosphate Dehydrogenase and Lactate Dehydrogenase
Glyceraldehyde-3-Phosphate Dehydrogenase is an enzyme, found in the cytosol of all the cells, whether the cell is of eukaryotic or prokaryotic. This is an NAD+ linked enzyme of the glycolytic pathway, catalyzing the conversion of Glyceraldehydes-3-Phosphate to 1, 3-Bisphosphoglycerate.
During the conversion of each molecule of Glyceraldehyde-3-Phosphare to 1,3-Bisphosphoglycerate, one molecule of NADH is produced. Glyceraldehyde-3-phosphate Dehydrogenase is highly sensitive to arsenic poisoning, as arsenate acts as a substrate analog to the enzyme and prevents the action of the enzyme, as a result of which no ATP is produced in the next step.
Lactate Dehydrogenase or Lactic Acid Dehydrogenase is also an NAD+ linked enzyme, found in the cytosol of all the cells. However, LD is predominant in the cells of the tissues like the heart, lungs, kidney, muscles and RBC, where it's involved in the regeneration of NAD+ from NADH, allowing the glycolysis.
Thus, liberated NAD+ is used up by the Glyceraldehyde-3-Phosphate. Lactate dehydrogenase is most important in the cell, where mitochondria are absent and the cell can not produce energy through TCA cycle/Electron Transport Chain (eg. Red Blood Cells), because glycolysis is the only mean for energy production.
Continuous energy production through glycolysis requires a constant supply of NAD+, and therefore lactate dehydrogenase maintains the NAD+ level in those cells. Lactate Dehydrogenase catalyzes the conversion of Pyruvate, the end product of glycolysis to Lactate, regenerating NAD+ from NADH.
Glutamate Dehydrogenase Inhibitor
Alcohol Dehydrogenase and Aldehyde Dehydrogenase
These are NAD+ dependent enzymes, mostly found in the stomach and kidney. Though, they are found in all the tissues but are predominant in the stomach and kidney . Alcohol Dehydrogenase is a cytosolic enzyme while Aldehyde Dehydrogenase is a mitochondrial enzyme. When you drink alcohol, 2-8% is excreted from the urine and sweating and rest of the amount is metabolized to produce energy, with the help of these two enzymes.
Alcohol Dehydrogenase catalyzes the conversion of alcohol to the acetaldehyde while Aldehyde Dehydrogenase converts toxic acetaldehyde to the non-toxic acetate. Thus formed acetate is then converted to the acetyl-CoA, which enters into the TCA cycle for further metabolism.
Pyruvate Dehydrogenase Complex
Pyruvate Dehydrogenase of PDH Complex
Pyruvate Dehydrogenase is also an NAD+ linked enzyme, involved in the glucose metabolism, connecting glycolysis with the TCA cycle. It converts the glycolytic end product pyruvate to acetyl CoA, a substrate of the TCA cycle. PDH is a multi-sub unit complex enzyme (PDH complex), composed of three different enzymes. The second enzyme is Dihydrolipoyl Transferase and the third enzyme is Dihydrolipoyl Dehydrogenase. The reaction catalyzed by Pyruvate Dehydrogenase enzyme is an irreversible reaction, releasing one molecule of CO2. The reaction catalyzed by the PDH complex is an "Oxidative Decarboxylation".
TCA Cycle Dehydrogenase Enzymes
Isocitrate Dehydrogenase is the third enzyme of the TCA cycle, catalyzing the conversion of Isocitrate to the α-Keto Glutarate. This NAD+ linked enzyme is found in the mitochondrial matrix and converts one molecule of NAD+ to the NADH. The reaction catalyzed is the "oxidative decarboxylation" reaction, which removes one molecule of CO2 from the substrate isocitrate.
α-Keto Glutarate Dehydrogenase is another NAD+ dependent mitochondrial enzyme, catalyzing the fourth step of the TCA cycle. It converts α-Keto Glutarate to the Succinyl-CoA. During this oxidative decarboxylation reaction, one molecule of NAD+ is consumed to produce one molecule of NADH with the release of another molecule of CO2.
Succinate Dehydrogenase is not an NAD+ dependent, mitochondrial membrane bound enzyme. It catalyzes the conversion of succinyl-CoA to the Fumarate, the sixth step of the TCA cycle. However, Malate Dehydrogenase is an NAD+ dependent enzyme that catalyzes the conversion of L-Malate to the Oxaloacetate, the last step (8th reaction) of the TCA cycle.
Catabolism of Glutamine By Glutamate Dehydrogenase
Glutamate Dehydrogenase is an NAD+ linked enzyme, located in the mitochondrial matrix. This enzyme links the Carbon and Nitrogen metabolism together. Thus, Glutamate Dehydrogenase acts as a branch point of carbon and nitrogen metabolism. It catalyzes the deamination of L-Glutamate to form α-Keto Glutarate, releasing amino group in the form of ammonia. The α-Keto Glutarate can be converted to Succinyl-CoA through the TCA cycle and the ammonia is converted to the urea through urea cycle, from where it is excreted out. This reaction is a reversible reaction