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Glucose metabolism, Krebs cycle, electron transfer chain...
The balk of 85-90% of its caloric needs, the body satisfies by burning monosaccharides, primarily glucose, and fatty acids (roughly in even proportion between the two). As soon as it enters the cytosol, glucose is converted, irreversibly, into glucose 6-phosphate (G6P), the initial chemical metabolite of the anaerobic (not requiring oxygen) phase of the cellular glucose metabolism, called glycolysis.
Branching out from glycolysis at this stage is a complex major pathway converting glucose 6-phosphate into 5-carbon monosaccharides (pentoses) - including ribose and deoxyribose for nucleotide synthesis (pentose phosphate pathway).
The end metabolite of glycolysis of a single glucose molecule is a pair of three-carbon molecules called pyruvate (or pyruvic acid). In the process, net energy obtained from re-arranging molecular bonds is preserved in the form of two
adenosine tri-phosphate (ATP) molecules.
made of adenine, ribose and three phosphate groups. ATP is the basic form of cellular energy. This energy is easily accessed by removing one phosphate group (i.e. conversion by hydrolysis of ATP to ADP - adenosine di-phosphate - which still can release energy by conversion to adenosine mono-phosphate, AMP), and used for cellular anabolic reactions.
Glycolysis of every glucose molecule also creates two molecules of NADH, the reduced (i.e. with added electrons) form of vitamin B3 based coenzyme nicotinamide adenine dinucleotide (NAD+). Most of these NADH molecules move from the cytosol to mitochondria, where they are used as high-energy electron donors fueling electron transport chain - the main energy producing cellular process.
But there is still a lot of energy remaining in the molecular bonds of pyruvate. It undergoes transitional reaction to
(where CoA stands for the vitamin-B5-derived coenzyme A), which also moves from cytosol to mitochondria. There it reacts with oxaloacetate to form citrate, which initiates the complex set of reactions called Krebscycle (a.k.a. citric acid cycle, or tricarboxylic acid cycle, TCA).
The transitional reaction from pyruvate to acetyl CoA creates another two NADH molecules (one for each pyruvate molecule obtained from glucose molecule), as well as some carbon dioxide.
However, the acetyl-COA-initiated Krebs cycle produces as many as six NADH molecules (three per acetyl-CoA molecule produced from each pyruvate) and two FADH2 (reduced form of FAD, flavine adenine dinucleotide, a vitamin-B2-derived enzyme cofactor) molecules, another high-energy electron donor to be used to fuel electron transport chain.
In addition, the cycle nets two more ATP molecules. It also produces most of the carbon dioxide (CO2) created by cellular respiration. Carbon dioxide is used for some cellular reactions (urea cycle), but it is mainly disposed of by the cell, to be picked up by venous blood, taken to the lungs and exhaled.
The final, most important sequence in the process of energy production in mitochondria is the electron transport chain, or oxidative phosphorylation (adding phosphate group to an organic molecule). In it, high-energy electron donors like NADH and FADH2, created during glycolysis and Krebs cycle, initiate a series of redox reactions (reduction-oxidation, or gaining and loosing electrons, respectively) across the inner mitochondrial membrane and surrounding fluid.
The flow of electrons, accompanied with flow of protons (i.e. ionized hydrogen atoms) from one acceptor/donor to another - among the principal carriers being cytochrome c protein (its redox element is an iron atom within its heme group), coenzyme Q10 (reduced to ubiquinone, a.k.a. coenzyme Q), flavin cofactors, iron-sulfur clusters and cytochrome a and b - brings electrons from higher to lower energy level, with the released energy driving protons to the outer side of the inner mitochondrial membrane.
As they accumulate on one side of the membrane, it creates electrochemical gradient - or, plainly, electrical potential - pulling the protons back toward the membrane. They pass through
ATP synthase enzymes -
a complex protein structure forming openings in the membrane - which use the energy of proton flow for ATP synthesis from ADP and phosphate.
While the actual figures vary with both, chemical model and individual biochemistry, it is usually considered that each NADH molecule entering electron transport chain results in 3 ATP molecules generated, each FADH2 generates 2 ATP molecules, and each GTP (guanosine triphosphate, another electron donor produced by Krebs cycle) 1 ATP unit.
Thus, burning each glucose molecule, with the total of 10 NADH (2 by glycolysis, 2 in pyruvate-to-acetyl CoA conversion, and 6 in Krebs cycle), 2 FADH2 and 2 GTP (guanosine triphosphate, another electron donor produced by Krebs cycle) molecules, both produced by Krebs cycle, that are generated through both glycolysis and Krebs cycle, creates 36 ATP molecules through the electron transport chain. Adding to it 2 ATP units produced during glycolysis, burning down each glucose molecule contributes 38 ATP units.
At the end of the chain, the final electron acceptor is oxygen, which then combines with two protons (i.e. hydrogen ions missing electron), to form water molecule. In the absence of oxygen, accumulation of electrons neutralizes electrochemical gradient, stopping the flow of protons, ATP synthesis, and with it the principal energy source for the cell. Cells die massively throughout the body, and the vital functions are quickly shot down.
That is why we have to keep breathing: to let the electrons in mitochondria flow, which in turn allows ATP synthase enzymes in your mitochondria to create usable energy needed to support cellular functions.
Oxidative phosphorylation in the electron transfer chain, initiated by electron donors created through glycolysis, pyruvate-to-acetyl CoA conversion and Krebs cycle from a single glucose molecule, yields 34 ATP molecules - compared to only 4 ATP molecules generated in these three preceding cycles combined.
It, however, also produces most of the
reactive oxygen species,
like superoxide and hydrogen peroxide, created during cellular respiration. If not deactivated by sufficient level of cellular antioxidants, these volatile molecular forms can damage - either directly or by initiating chains of uncontrolled oxidative reactions - structural and functional integrity of the cell. If extensive enough, this can cause or contribute to various symptoms, accelerated aging, and/or development of a degenerative disease.
The other two main metabolites of digested food, amino and fatty acids, have similar fate as sugars when they are burned for energy. Through different pathways, they also enter Krebs cycle, feeding the electron transport chain. The main difference vs. sugar metabolism is that amino acids and fatty acids are in significantly greater degree used for synthesis of a great variety of molecular structures needed by the cell (anabolism).
That is particularly the case with amino acid metabolism, producing thousands of body's proteins.