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Body metabolism

Body metabolism - Cellular metabolism  Sugars  Amino acids
Fatty acids - Metabolic type

It matters a lot how good is the food you eat, and how efficient is your digestion. But it still isn't enough to guarantee health. It is the smallest piece of the puzzle - your cellular metabolism - that ultimately determines how good you feel, and how long you live. As your cells assimilate small molecules of proteins, fats and carbohydrates broken down by digestion - i.e. amino acids, fatty acids and monosaccharides - the question of whether they will be able to use them efficiently for their - and yours - wellbeing is still unanswered.

 And the answer depends on the final outcome of the incredibly complex chemical interaction of billions of molecules inside each of your cells. The importance of this process is summed up in its two-word description: cellular respiration. It is literally what is keeping your cells, and your body, alive.

The entire process of cellular respiration can be summarized in a single sentence. Assimilated monomers (amino and fatty acids, monosaccharides) are used either for synthesis of needed molecules (anabolism), or further degraded to free the energy needed for the synthesis (catabolism).

Of course, there's much more to it. The big picture shows all catabolized monomers - fatty and amino acids, as well as simple sugars - going through a 3-step process:

1 - conversion to a simple compound called acetyl CoA, generating some adenosine triphosphate (ATP, cellular energy unit), some high-energy electron carriers (NADH, FADH2), some hydrogen ions (i.e. protons, H+) and carbon dioxide (CO2) in the process

2 - oxidation of acetyl CoA through a cyclic series of reactions in the mitochondrial matrix, called Krebs cycle (also citric acid cycle, or tricarboxylic acid cycle, TCA), which creates more high-energy electron carriers (NADH, FADH2 and GTP - guanosine triphosphate, another electron donor produced by Krebs cycle), hydrogen ions and carbon dioxide, and

3 - channeling high-energy electrons from NADH, FADH2 and GTP through a series of reactions called electron-transport chain, or oxidative phosphorylation, to create proton flow through the inner mitochondrial membrane, used to generate major influx of ATP units by ATP synthase enzyme, with oxygen enabling continuation of this process by removing (i.e. accepting) end-point electrons and then combining with protons to form water (H2O)

Diagram below is the very basic illustration of cellular metabolism; that is, how cells use digested food molecules assimilated from the bloodstream in catabolic (energy-producing break-up of complex molecules) and anabolic (energy-requiring molecular synthesis) phase of their metabolism. The major metabolic pathways are summarized in the table preceding it.




Glycolysis - splits glucose molecule into two pyruvate molecules, in the cell's cytosol, producing some ATP and metabolites feeding both Krebs cycle and electron transport chain

Protein synthesis - assembling amino acid into complex molecular structures  in the cytosolic and EP ribosomes, according to the code transferred to them from the nucleus (DNA) by the RNA

β-oxidation - dismantles fatty acid molecule into acetyl-CoA molecules, through a cyclic reaction inside mitochondria, feeding Krebs cycle

Lipid synthesis - cyclic reaction reverse to β-oxidation, taking place in the cytosol (mediated by the fatty acid synthase enzyme complex, producing saturated palmitic acid) and in the endoplasmic reticulum where it is modified to longer and/or unsaturated fatty acids*

Krebs cycle (citric acid cycle, tricarboxylic acid cycle) - breaks acetyl-CoA molecule, obtained from pyruvate in a transitional reaction, or from β-oxidation, through the chain of mainly oxidative reactions in the mitochondria, also producing some ATP and high-energy-electron donors

Nucleotide synthesis - complex series of reactions including synthesis of purine and pirimidine bases from amino acids (i.e. purine and pirimidine pathways), as well as pentose phosphate pathway, in which the pentose sugars (ribose, deoxyribose) and phosphate group making the RNA/DNA strands are produced (also the PRPP sugar phosphate, the key metabolite in purine/pirimidine synthesis)

Electron transport chain (oxidative phosphorylation) - takes high-energy electrons from the initial donor-molecules produced by the previous three pathways through a series of inter-molecular transfers around the inner mitochondrial membrane, to lower energy levels, using their energy to produce most of cellular ATP

Glycogenesis - converts excess glucose
into its quick-access storage form, glycogen (mainly in the liver and muscle cells); glycogen generated by the liver is the main source of blood glucose

*(fatty acid synthesis is initiated at sufficiently high levels of mitochondrial acetyl CoA, produced mainly from the monomers created by digestion of dietary carbohydrates and fats; excess fatty acids synthesized are bundled into triglycerides - i.e. triacylglycrol - and stored into fat tissue)

There are many other metabolic pathways, both catabolic and anabolic. Very few, if any, comprise only a single type of reactions (i.e. either breaking down, or synthesis). It is the overall effect that determines the nature of the pathway. For the cell, both catabolism and anabolism are pretty much a part of one same purpose - staying alive.

Cellular metabolism: Amino acids from digested proteins are added to the cell's pool. Some are used directly for protein synthesis in ribosomes (tiny cell's organelles scattered mainly throughout cytosol (fluid between cell's nucleus and the outer membrane), but also bound to the membranes of endoplasmic reticulum). Some are transformed into amino acids needed by the cell by transamination, and the rest is degraded by transferring their amino groups to glutamine (formed mainly in the muscle tissue and transported to liver for deamination and removal of toxic ammonia through urea cycle), while their carbon skeletons are turned into pyruvate, acetyl CoA, or into one of Krebs cycle intermediaries. Amino acid components are also used for the synthesis of purine and pyrimidine bases, which are built from amino groups and ammonia (from glutamine). The bases combine with 5-carbon monosaccharides (pentoses),  specifically ribose and deoxyribose, produced in the Pentose phosphate cycle, to form nucleotides - the essential building blocks of RNA and DNA. Fatty acids from digested fats are also added to the cells' pool, and either used directly for lipid synthesis, or combined with CoA (coenzyme A) to form acyl CoA, which in a 4-stage enzymatic reaction (β-oxidation) loses two carbon groups from its carbon-group chain to form acetyl CoA; the cycle repeats until all carbon groups from the fatty acid chain are transformed into acetyl CoA. Acetyl CoA can either enter Krebs cycle for energy production, or be transported via citrate shuttle out to cytosol and used for fatty acid synthesis. Oxidation and synthesis of fatty acids are coordinately regulated by hormones and by enzymatic activity, both guided by the levels of specific metabolites. Simple sugars (monosaccharides) from digested carbohydrates are converted to glucose 6-phosphate immediately after entering cytosol; from there, the two most significant routes are: (1) transformation to pyruvate (glycolysis), which is converted to acetyl CoA to enter Krebs cycle, and (2) transformation to 5-carbon sugar molecules (pentoses) for DNA/RNA synthesis. Both glycolysis and Krebs cycle produce some energy in the form of adenosine triphosphate (ATP) and, more importantly, feed the main main source of cellular energy, electron transport chain, with high-energy electron donors (NADH, FADH2).

The above diagram shows only the major pathways of the three generalized food metabolites absorbed at the cellular level: amino acids, fatty acids and simple sugars. In reality, the cell processes over 20 different amino acids, nearly as many fatty acids and three simple sugars: glucose, fructose and galactose. The above scheme is immensely simplified and incomplete representation of the entirety of cellular metabolism, but it is useful for grasping the big picture.

In addition to the major pathways, it identifies the three central metabolites of cellular respiration:

(1) glucose-6-phosphate (G6P), branching out into two major metabolic pathways, one catabolic, leading to conversion to pyruvate (glycolysis), then to acetyl CoA, Krebs cycle and electron transfer chain, while the other anabolic, leading to conversion into 5-carbon sugar molecules (pentoses) needed to build DNA and RNA structure

(2) pyruvate, the end result of glycolysis, and link to acetyl CoA

(3) acetyl CoA (acetyl coenzyme A), common metabolic intermediary to oxidation of glucose, fatty acids and some amino acids; its reaction with oxaloacetate produces citrate, initiating two major metabolic pathways: Krebs cycle and fatty acid synthesis

Behind this big picture, there are many smaller, auxiliary and minor metabolic pathways, catalyzed by thousands of enzymes. Many of these pathways partly overlap, or have one or more alternative pathways, which are activated if the preferred one is inefficient or not functioning. This, in turn, changes the overall metabolic outcome, possibly significantly. Many pathways do interfere with other pathways to some extent. Also, many reactions are reversible, so the cell can switch metabolic paths back and forth, according to its needs.

An actual image of the cellular metabolism is a highly coordinated chaos of billions of molecules and sub-molecular entities continuously interacting both, within the cell and in its immediate surroundings. To make it all possible, there

has to be sufficient energy available wherever it is needed.

In general, degradation (catabolism) of disposable complex molecules into simpler molecules provides the energy for synthesis (anabolism) of more complex molecules needed by the cell.

Any disturbance in the efficacy of major catabolic pathways - glycolysis, β-oxidation and amino acid degradation fueling glycolysis or Krebs cycle, or electron transport chain - will negatively affect cell's viability.

A common cause of such disturbances are

inhibitions in the cell's enzymatic activity

by environmental toxins, oxidative damage and nutritional deficiencies. The enzymes are the lifeline of cellular respiration; if they are damaged or incapacitated, cellular processes that they carry dwindle. It can be anything from splitting the molecules for energy, to the synthesis of cellular structures.

As a result of inefficient enzymatic action, cells become less viable, sluggish, and more vulnerable to further damage; at worst, they die prematurely, or disassociate from the body, possibly turning into some form of malignant growth. If significant in the extent and duration, such obstructions of cellular metabolism will manifest as various symptoms of compromised health and/or degenerative diseases.

In other words, all the good, and the bad happening to your health comes from this tiny microcosm - the body cell. This warrants a bit closer look into cellular metabolic pathways for each of the three major macronutrients.

Let's start with the sweet stuff: the sugar metabolism.