Biochemistry - The Chemical Reactions of Living Cells, Volume 2 - D. Metzler 1980

How electrons meet oxygen, how ATP is generated in the process, and some related phenomena
Electron transport chain and oxidative phosphorylation
Mitochondrial architecture

One of the central questions in modern biochemistry is how the flow of electrons along a chain of carriers is coupled to the synthesis of ATP. This question is of paramount importance, as the majority of ATP produced in aerobic and certain anaerobic organisms is generated precisely through Oxidative Phosphorylation. Furthermore, the energy captured during Photosynthesis is utilized to synthesize ATP via a very similar mechanism. The Mechanism of ATP generation may be intimately linked to membrane function during ion transport. It is entirely possible that The Mechanism of Oxidative phosphorylation is, in a sense, the reverse of the mechanism by which ATP energy is used to drive Muscle contraction.

Throughout the 1940s, as it became clear that The formation of ATP from ADP and inorganic phosphate is coupled to electron transport in Cell/35.html">Mitochondria, biochemists began making their first attempts to "take the system apart" in order to elucidate its molecular mechanisms. However, nature sometimes fiercely resists attempts to yield her secrets, and the Current state of affairs was aptly summarized by Efraim Racker: "Anyone who is not confused by Structure/149.html">The problem of oxidative phosphorylation simply does not understand the situation [58]." This confusion is by no means due to a lack of effort or imagination. A multitude of diverse hypotheses regarding the Mechanism of Oxidative phosphorylation have been published, yet no one has provided a fully convincing explanation. Moreover, the failure to account for oxidative phosphorylation using conventional chemical concepts led to the proposal of somewhat vague hypotheses with rather fanciful names. In contrast to what was dubbed the "chemical hypothesis," the "chemiosmotic hypothesis" and the "mechanochemical coupling hypothesis" were put forward. Here, the "chemical hypothesis" refers to the formation of discrete, though as yet unidentified, intermediate "high-energy" chemical compounds.

In Bacteria, Electron Transport and oxidative phosphorylation are presumably localized in the Cytoplasmic membranes. In Eukaryotic Cells, these processes occur primarily in mitochondria. Therefore, we will begin with a closer look at mitochondria—the "powerhouses of The Cell."

A typical mitochondrion is roughly the same size as an E. coli cell, though the shape and size of these Organelles can vary considerably. In all cases, a mitochondrion is bounded by two closed membranes (outer and inner), each ~ 5–7 nm thick (Fig. 10-9). In the Liver, the inner membrane is poorly developed and the bulk of the space is filled with the matrix, whereas in cardiac muscle mitochondria, the inner membrane is far more extensively folded and The rate of oxidative phosphorylation is correspondingly higher. The Enzymes catalyzing the reactions of The Tricarboxylic Acid Cycle are also more active in Heart muscle mitochondria. Furthermore, given the high METABOLIC ACTIVITY OF cardiac muscle, nearly one-third of its total mass is accounted for by mitochondria. A typical heart muscle mitochondrion has a volume of 0,55 мк³; for every cubic micron of mitochondrial volume, there are 89 мк² of inner mitochondrial membrane surface [62].

Mitochondria can swell and contract, and alongside the orthodox conformation typically observed in Cytology/cytology/93.html">ELECTRON MICROGRAPHS OF osmium-fixed specimens, several other forms have been described. In condensed Conformations, mitochondria exhibit swollen cristae, a drastically reduced matrix volume, and an expanded inner membrane surface area. Actively respiring mitochondria prepared for Electron Microscopy adopt a state designated as the “energized” or “energized-twisted” configuration [63].

Mitochondrial outer membranes can be ruptured by osmotic Shock and separated from the inner membranes [64]. Fractionation analysis reveals that outer membranes possess a lower density (∼1.1 g/cm³) than inner membranes. They are readily permeable to most substances with a Molecular Weight of 10,000 and below. The phospholipid-to-protein ratio is quite high (∼0.82 by weight); extraction of Phospholipids with acetone disrupts the membrane. These phospholipids are characterized by a low cardiolipin content and high levels of phosphoinositide and Cholesterol. Ubiquinone is absent from these membranes. The inner membrane (density ∼1.2 g/cm³) is impermeable to numerous compounds. In fact, with the exception of neutral molecules with a molecular weight <150, permeability to all Other Compounds is strictly regulated. The phospholipid-to-protein ratio in the inner membrane is low (∼0.27); cardiolipin accounts for ~20% of the total phospholipids. Ubiquinone and Other components of the Respiratory Chain reside within the inner membrane.

Another hallmark of The inner mitochondrial membrane is the presence, under certain conditions, of projections on its matrix-facing surface. Fernández-Morán, who discovered these particles in 1962, hypothesized that they might harbor the enzymes of The electron transport system. However, subsequent research demonstrated this not to be the case. Instead, these spherical particles, possessing a molecular weight of ∼85,000 and attached to the membrane by a stalk, exhibit ATPase activity. This enzymatic activity presumably holds the key to ATP synthesis during oxidative phosphorylation. The protein comprising these particles is now recognized as coupling factor F₁ (or ATP synthase). Because such knob-like protrusions on the inner membrane surface are visible only in preparations negatively stained with phosphotungstate, their presence in intact mitochondria remains a subject of debate. They may simply arise as artifacts during the staining process, representing newly formed aggregates of enzymes previously embedded within the inner membrane.

In addition to Ribosomes (mitoribosomes) resembling bacterial ribosomes and small circular DNA molecules, mitochondria contain varying numbers of dense calcium phosphate granules [65], consisting of either Ca₃(PO₄)₂ or hydroxyapatite (Addendum 5-D).