The science behind energy production in the body

The Krebs’ Cycle 

http://nutritionreview.org/2013/04/krebs-cycle-intermediates/

All cells must produce energy to survive. Hans A. Krebs first elucidated the process of cells converting food into energy, the Citric Acid Cycle, in 1937. Krebs proposed a specific metabolic pathway within the cells to account for the oxidation of the basic components of food – carbohydrates, protein and fats – w for energy. The Krebs’ cycle takes place inside the mitochondria or ‘power plant’ of cells and provides energy required for the organism to function.
Mitochondria are found in all cells in the human body, with the exception of mature red blood cells. The primary function of these tiny organelles (each cell contains between 500 and 2,000 mitochondria) is to convert energy found in nutrient molecules and store it in the form of adenosine triphosphate (ATP). ATP is the universal energy-yielding molecule used by enzymes to perform a wide range of cellular functions. Humans cannot survive, even for a second, without a constant supply of ATP.
In order to carry out energy conversion, mitochondria require oxygen. The purpose of our respiratory and circulatory systems is to deliver oxygen to the tissues for use by mitochondria, and to eliminate carbon dioxide. The consumption of oxygen by mitochondria is called cellular respiration.
In simple terms, the Krebs’ cycle metabolizes acetyl coenzyme A into citric acid and then runs through a complex series of biological oxidations, producing free hydrogen ions. A net of two molecules of ATP is created at this stage in the Krebs’ cycle. The hydrogen ions then enter a biochemical chain, known as oxidative phosphorylation, which is a highly efficient aerobic energy generator. Oxidative phosphorylation generates 36 molecules of ATP during a sequence of steps that combine hydrogen electrons to molecular oxygen to form water. Therefore, each molecule of citric acid that rotates through the Krebs’ cycle, generates 38 molecules of ATP for tissue fuel. (1)
There are different points where metabolites enter the Krebs’ cycle. Most of the products of protein, carbohydrates and fat metabolism are reduced to the molecule acetyl coenzyme A that enters the Krebs’ cycle. Glucose, the primary fuel in the body, is first metabolized into pyruvic acid and then into acetyl coenzyme A. The breakdown of the glucose molecule forms two molecules of ATP for energy in the Embden Meyerhof pathway process of glycolysis. On the other hand, amino acids and some chained fatty acids can be metabolized into Krebs intermediates and enter the cycle at several points.
When oxygen is unavailable or the Krebs’ cycle is inhibited, the body shifts its energy production from the Krebs’ cycle to the Embden Meyerhof pathway of glycolysis, a very inefficient way of making energy.
As well as producing far less energy, glycolysis also produces lactic acid as a byproduct. Increased lactic acid is a common acidotic condition that can be caused by a variety of metabolic problems. Accumulation of lactic acid in muscle tissue produces the pain and inflammation we experience after exercising. While untrained individuals have a low lactate threshold, highly trained, elite athletes are extremely efficient at converting lactate to glucose and therefore have lower lactate levels. (2,3)

Step 1 The acetic acid subunit of acetyl CoA is combined with oxaloacetate to form a molecule of citrate. Acetyl coenzyme A acts only as a transporter of acetic acid from one enzyme to another. After Step 1, the coenzyme is released by hydrolysis to combine with another acetic acid molecule and begin the Krebs’ Cycle again.
Step 2 The citric acid molecule undergoes an isomerization. A hydroxyl group and a hydrogen molecule are removed from the citrate structure in the form of water. The two carbons form a double bond until the water molecule is added back. Only now, the hydroxyl group and hydrogen molecule are reversed with respect to the original structure of the citrate molecule. Thus, isocitrate is formed.
Step 3 The isocitrate molecule is oxidized by a NAD molecule. The NAD molecule is then reduced by the hydrogen atom and the hydroxyl group. The NAD binds with a hydrogen atom and carries off the other hydrogen atom leaving a carbonyl group. This structure is very unstable, so a molecule of CO2 is released, creating alpha-ketoglutarate.
Step 4 In this step, coenzyme A, returns to oxidize alpha-ketoglutarate. A molecule of NAD is reduced again to form NADH and leaves with another hydrogen. This instability causes a carbonyl group to be released as carbon dioxide and a thioester bond is formed in its place between the former alpha-ketoglutarate and coenzyme A to create a molecule of succinyl-coenzyme A complex.
Step 5 A water molecule sheds its hydrogen atoms to coenzyme A. Then, a free-floating phosphate group displaces coenzyme A and forms a bond with the succinyl complex. The phosphate is then transferred to a molecule of ADP to produce an energy molecule of ATP. It leaves behind a molecule of succinate.
Step 6 In this step, succinate is oxidized by a molecule of FAD (Flavin Adenine Dinucleotide). The FAD removes two hydrogen atoms from the succinate and forms a double bond between the two carbon atoms to create fumarate.
Step 7 An enzyme adds water to the fumarate molecule to form malate. The malate is created by adding one hydrogen atom to a carbon atom and then adding a hydroxyl group to a carbon next to a terminal carbonyl group.
Step 8 In this final step, the malate molecule is oxidized by a NAD molecule. The carbon that carried the hydroxyl group is now converted into a carbonyl group. The end product is oxaloacetate which can then combine with acetyl-coenzyme A and begin the Krebs’ Cycle all over again.

Amino Acid Energy Boosters

Amino acids can be converted via the Krebs’ cycle to glucose for energy or for storage as glycogen and fat. During times of increased stress due to trauma, exercise, starvation and disease states, amino acids can be catabolized into intermediates to produce energy for muscular contraction. This is why taking free form amino acids can boost energy levels and help to prevent hypoglycemia. Additionally, low levels of particular Krebs’ cycle factors may diminish amino acid availability and require supplementation to generate energy and correct metabolic dysfunction. (4-6)

Krebs’ Cycle Shutdown 

Under normal conditions all the reactions in the Krebs’ cycle proceed smoothly and ATP is generated without the excessive production of any harmful byproducts. However, different conditions can alter Krebs’ cycle chemistry, causing it to shut down normal energy production. For example, ifcatabolic pathwayssuch as stress, illness, or the synthesis of amino acids consume vital intermediary substances, then the Krebs’ cycle can come to a grinding halt. Interconversions of Krebs’ cycle intermediates are controlled by enzymes that often require vitamin-derived cofactors and minerals to operate. For example, pyruvate is the anaerobic breakdown product of glucose. Its further conversion to acetyl-CoA requires cofactors derived from thiamin, riboflavin, niacin, lipoic acid, and pantothenic acid. When these nutrients are deficient, problems result that disrupt mitochondrial energy production. (7)
In some individuals, a deficiency in the enzyme activity of the Krebs’ cycle may occur when Krebs’ cycle enzymes are bound up by various xenobiotics or endotoxins. The inability of pyruvic acid to enter into the cycle for energy production can shut down the second half of the Krebs’ cycle and create a lactic acid buildup. With increased acidification comes a localized decrease in oxygenation of the tissues, leading to muscle fatigue and other characteristic symptoms.
Researchers have concluded that prolonged exercise to fatigue results in carbohydrate and glycogen depletion that reduces levels of three-carbon compounds from glycolysis. This produces an energy deficiency as the Krebs’ cycle shuts down and lowers aerobic capacity. (8)