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Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine nucleobase and the other, nicotinamide. NAD exists in two forms: an oxidized and reduced form, abbreviated as NAD + and NADH (H for hydrogen), respectively.
Glycolysis is the metabolic pathway that converts glucose (C 6 H 12 O 6) into pyruvate and, in most organisms, occurs in the liquid part of cells (the cytosol). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH). [1]
Typical eukaryotic cell. Cellular respiration is the process by which biological fuels are oxidized in the presence of an inorganic electron acceptor, such as oxygen, to drive the bulk production of adenosine triphosphate (ATP), which contains energy.
When sufficient oxygen is not present in the muscle cells for further oxidation of pyruvate and NADH produced in glycolysis, NAD+ is regenerated from NADH by reduction of pyruvate to lactate. [4] Lactate is converted to pyruvate by the enzyme lactate dehydrogenase. [3] The standard free energy change of the reaction is -25.1 kJ/mol. [6]
In eukaryotes, NADH is the most important electron donor. The associated electron transport chain is NADH → Complex I → Q → Complex III → cytochrome c → Complex IV → O 2 where Complexes I, III and IV are proton pumps, while Q and cytochrome c are mobile electron carriers. The electron acceptor for this process is molecular oxygen.
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. NADH is a reducing equivalent that stores electrons generated in the cytoplasm during glycolysis. NADH must be transported into the mitochondria to enter the oxidative phosphorylation pathway.
The energy from the acetyl group, in the form of electrons, is used to reduce NAD+ and FAD to NADH and FADH 2, respectively. NADH and FADH 2 contain the stored energy harnessed from the initial glucose molecule and is used in the electron transport chain where the bulk of the ATP is produced. [1]
The chain of redox reactions driving the flow of electrons through the electron transport chain, from electron donors such as NADH to electron acceptors such as oxygen and hydrogen (protons), is an exergonic process – it releases energy, whereas the synthesis of ATP is an endergonic process, which requires an input of energy.