Dehydrogenases are a class of enzymes that catalyze essential chemical reactions within living cells. These biological catalysts facilitate energy transfer by removing hydrogen atoms from specific molecules, a process known as dehydrogenation. This action allows the cell to extract usable energy from food and manage molecular building blocks necessary for growth and repair. Dehydrogenases are central to metabolism, impacting everything from energy production to detoxification.
The Chemical Mechanism of Dehydrogenation
Dehydrogenases operate by facilitating a specific type of chemical exchange called an oxidation-reduction (redox) reaction. In this process, the enzyme removes a pair of hydrogen atoms from a substrate molecule, effectively oxidizing it. This transfer involves the movement of a hydride ion—which consists of a hydrogen nucleus and two high-energy electrons—to a receiving molecule.
Dehydrogenation requires the participation of specific cofactors that act as electron carriers. The most prominent are Nicotinamide Adenine Dinucleotide (\(NAD^+\)) and its phosphorylated relative, Nicotinamide Adenine Dinucleotide Phosphate (\(NADP^+\)). During the reaction, the enzyme transfers the hydride ion from the substrate to the oxidized cofactor, converting \(NAD^+\) to \(NADH\) or \(NADP^+\) to \(NADPH\).
These cofactors are chemically distinct and serve different purposes within the cell. \(NAD^+\) is primarily involved in catabolic, energy-releasing pathways where molecules are broken down to generate power. Conversely, \(NADP^+\) is predominantly used in anabolic, or building, pathways, such as the synthesis of fatty acids and protection against oxidative stress. The newly formed \(NADH\) and \(NADPH\) carry the high-energy electrons, ready to donate them to other cellular processes.
Essential Roles in Cellular Energy Production
The \(NADH\) and \(FADH_2\) molecules generated by dehydrogenases drive the cell’s main energy-generating system. Energy production begins with glycolysis, where Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalyzes a crucial step. GAPDH converts glyceraldehyde-3-phosphate into 1,3-bisphosphoglycerate, a reaction that simultaneously reduces \(NAD^+\) to \(NADH\) and incorporates an inorganic phosphate into the substrate.
\(NADH\) then feeds into the Citric Acid Cycle, also known as the Krebs Cycle. The Pyruvate Dehydrogenase complex acts as a bridge, converting pyruvate from glycolysis into Acetyl-CoA, producing \(NADH\) within the mitochondria. Inside the cycle, enzymes like Isocitrate dehydrogenase and Malate dehydrogenase further oxidize the substrates, generating additional \(NADH\).
Succinate dehydrogenase is unique in the Citric Acid Cycle because it is permanently embedded in the inner mitochondrial membrane. This enzyme converts succinate to fumarate, reducing Flavin Adenine Dinucleotide (\(FAD\)) to \(FADH_2\). Unlike \(NADH\), \(FADH_2\) is immediately positioned to donate its electrons to the Electron Transport Chain (ETC) at Complex II.
The final purpose of electron carrier production is to power the ETC, the cell’s engine for generating Adenosine Triphosphate (ATP). Both \(NADH\) and \(FADH_2\) deliver their high-energy electrons to the complexes of the ETC, creating a proton gradient across the inner mitochondrial membrane. The flow of these protons back into the mitochondrial matrix through ATP synthase ultimately drives the synthesis of ATP, completing the process of energy extraction.
Dehydrogenases as Health Indicators and Detoxifiers
Specific dehydrogenases serve as indicators of health and perform detoxification functions. Alcohol Dehydrogenase (ADH) initiates the metabolism of ethanol in the liver. ADH catalyzes the oxidation of ethanol to acetaldehyde, a toxic compound, while reducing \(NAD^+\) to \(NADH\).
Aldehyde Dehydrogenase (ALDH) quickly converts the toxic acetaldehyde into harmless acetate. Genetic variations in these enzymes can lead to a slower metabolism of acetaldehyde, causing its accumulation and resulting in the unpleasant symptoms associated with a “hangover.” This detoxification pathway is a protective mechanism for the body.
Lactate Dehydrogenase (LDH) is widely distributed across many tissues, including the heart, liver, and skeletal muscle. The function of LDH is to interconvert pyruvate and lactate, a reaction important for regenerating \(NAD^+\) to keep glycolysis running in anaerobic conditions. When cells are damaged due to injury, disease, or lack of oxygen, LDH leaks from the damaged tissue into the bloodstream.
Measuring elevated levels of LDH in the blood serves as a general, non-specific biomarker for tissue injury, prompting further diagnostic testing. Glucose-6-Phosphate Dehydrogenase (G6PD) is crucial for maintaining the health of red blood cells. G6PD produces \(NADPH\), which is necessary to protect red blood cells from damage caused by reactive oxygen species.
A genetic deficiency in G6PD is the most common human enzyme defect worldwide. This deficiency leads to premature red blood cell breakdown (hemolytic anemia) when individuals are exposed to certain triggers like fava beans or specific medications.