Stages and Energetics of the Process
Broadly, cellular respiration can be divided into two closely linked components:
- Oxidation of substrates. The process is initiated by dehydrogenation reactions, which involve the removal of hydrogen atoms from organic molecules. This is followed by a multi-step electron transfer cascade, with oxygen as the final electron acceptor.
- Energy transformation. As electrons move down the respiratory chain, their free energy level decreases. The released energy is partitioned: a portion is inevitably lost as heat, while approximately 40% drives oxidative phosphorylation. This is the key mechanism for synthesizing the cellular energy currency—ATP—from ADP and inorganic phosphate.
First-Line Enzymes: Dehydrogenases
The initial step of cellular respiration is the dehydrogenation of substrates generated during catabolism. This task is carried out by dehydrogenases, which are localized primarily within the mitochondrial matrix.
Depending on their coenzyme structure, they are divided into two major groups: NAD-dependent and FAD-dependent dehydrogenases. Their mechanisms of action and chemical structures differ fundamentally.
Characteristics of NAD-Dependent Dehydrogenases
In this group of catalysts, the non-protein moiety is nicotinamide adenine dinucleotide ($NAD^+$). The molecule is a dinucleotide composed of an adenylic nucleotide (adenine, ribose, phosphate) and a nicotinamide nucleotide linked via their phosphate groups.
Key characteristics:
- Protein binding: The coenzyme is loosely bound to the apoenzyme. Upon reduction to $NADH$, it dissociates from the protein moiety to serve as a hydrogen donor for subsequent enzymes.
- Active center: The nicotinamide ring, which is a derivative of vitamin PP (B3).
- Reaction chemistry: In the oxidized state ($NAD^+$), the ring is aromatic and the nitrogen atom carries a positive charge with four bonds. During reduction, a hydride ion ($H^-$) attaches to the carbon in the para-position. This disrupts the aromaticity, redistributes the double bonds, and neutralizes the nitrogen charge. Notably, the second proton ($H^+$) is not incorporated into the molecule but remains in the surrounding medium.
A classic example is the conversion of malate to oxaloacetate by malate dehydrogenase. The reaction is: Malate + $NAD^+ \rightarrow$ Oxaloacetate + $NADH + H^+$
Characteristics of FAD-Dependent Dehydrogenases
The second group utilizes flavin adenine dinucleotide (FAD). Its structure is more complex, consisting of adenine, ribose, pyrophosphate, and riboflavin (composed of the sugar alcohol ribitol and an isoalloxazine ring).
Key characteristics:
- Protein binding: Covalent and extremely tight. The coenzyme cannot dissociate from the apoenzyme.
- Active center: A tricyclic system—the isoalloxazine ring (a derivative of vitamin B2).
- Reaction chemistry: In the oxidized state, the ring has a quinoid structure where two nitrogen atoms have double bonds. Upon reduction to $FADH_2$, two hydrogen atoms ($2H^+ + 2e^-$) attach to these nitrogen atoms, breaking the double bonds to form N-H bonds.
Because FAD is rigidly fixed to the enzyme, a second substrate—a mobile hydrogen acceptor—is required to continue the reaction. For all flavin enzymes, this role is fulfilled by ubiquinone (coenzyme Q).
An example is the oxidation of succinate to fumarate by succinate dehydrogenase. First, succinate is oxidized and FAD is reduced to $FADH_2$. Then, $FADH_2$ transfers its hydrogen to ubiquinone, yielding $QH_2$.