Bioenergetics

Bioenergetics, or biochemical thermodynamics is the study of the energy changes accompanying biochemical reactions.

Nonbiologic systems may utilize heat energy to perform work, but biologic systems are essentially isothermic and use chemical energy to power the living processes. Suitable fuel is required to provide the energy that enables the animal to carry out its normal processes.

How the organism obtains this energy from its food is basic to the understanding of normal nutrition and metabolism. Death from starvation occurs when available energy reserves are depleted and certain forms of malnutrition are associated with energy imbalance (kwashiorkor, marasmus). The rate of energy release, measured by the metabolic rate, is controlled by the thyroid hormones. Storage of energy results in obesity, one of the most common diseases of occidental society.

All life on the earth depend from the energy of sun. 0.02% of sun’s energy falls on the surface of earth. In the dependent from the ability of living organisms to use of sun’s energy all organisms are divided into 2 groups – autotrophic and heterotrophic.

Inorder to maintain living processes all organisms must obtain supplement of free energy from their environment. Autotrophic organisms couple their metabolism to some simple exergonic process in their surroundings, they are able to absorb the energy of sun light and carry out of the primary synthesis of organic compounds – photosynthesis due to the presence of chlorophill (eg, green plants), some autotrophic bacteria utilize the energy of the reaction Fe2+  Fe3+ for primary photosynthesis. Reaction of photosynthesis: 6CO2 + 6H2O + 2847kJ ↔ C6H12O6 + 6O2, where 2847kJ is an energy of sun, direct reaction occurs in plants (photosynthesis), reverse reaction occurs in animals and human and oxidation is called.

On the other hand heterotriphic organisms obtain free energy by coupling their metabolism to the breakdown of complex organic molecules in their environment. They must to receive these compounds eating different plants or animals.

The vital processes are a synthetic reactions, muscular contraction, nerve impulse conductions, active transport and cetera. They obtain energy by chemical linkage or coupling to oxidative reactions. Chemically, oxidation is defind as the removal of electrons and reduction as the gain of electrons.

Fe2+ ↔ Fe3+ where direct reaction is called oxidation (remove of electron); reverse reaction is called reduction (addition of electron). It follows that oxidation is always accompanied by reduction of an electron acceptor. This principle of oxidation-reduction applies equally to biochemical systems and is an important concept underlying understanding of the nature of biologic oxidation.

Although certain bacteria (anaerobis) survive in the absence of oxygen, the life of higher animals is absolutely dependent upon a supply of oxygen.

The principal use of oxygen is in respiration which nmay be defind as the process by which cells derive energy in the form of ATP from the controlled reaction of hydrogen with oxygen to form water. The terms exergonic and endergonic are used to indicate that a process is accompanied by loss or gain of free energy. The exergonic reactions are termed catabolism (the breakdown or oxidation of fuel molecules), whereas the synthetic reactions that build up substances are termed anabolism. The total of all is metabolism.

ATP plays a central role in the transfer of free energy from the exergonic to the endergonic processes.

There are 3 major sources of ATP taking part in energy conversation: 1) oxidative decarboxylation. This process is a greatest quantitative source of ATP in aerobic conditions. The free energy to drive this process comes from respiratory chain oxidation within mitochondria. 2) glycolysis is a formation of 2ATP results from the formation of lactate from 1 molecule of glucose. 3) the citric acid cycle yields 1 ATP.

Bioenergetic metabolism has a few stages:

1. the specific cleavage of the main nutrients (that results in formation of acetylCoA)

2. Crebs cycle (where the reduced forms of dehydrogenases are formed)

3. Biologic oxidation (in this process the reduced dehydrogenases are oxidized to give energy and water)

4. Oxidative phosphorylation (formation of ATP with usage of energy of biologic oxidation)

During 1 st stage proteins are hydrolyzed to aminoacids; lipids (mainly trigliceraides) to glycerol and FFA: carbohydrates (mainle glycogen and starch) to glucose. It occurs in gastrointestinal tract under action of hydrolases of salivary glands (alfa-amylase), pancreas (trypsin, chymotrypsin, carboxypeptidase, aminopeptidase, dipeptidases, tripeptidases, lipases, phospholipases, cholesterolesterase etc). then glucose, amino acids, glycerol and FFA are absorbed anf transformed in tissues. Glucose is catabolized to pyruvic acid; glycerol through phosphotrioses to pyruvic acid, amino acids to pyruvic or active acetic acid and FFA to active acetic acid. Pyruvic acid undergoes changes, giving active acetic acid (or acetylCoA). This reaction is named as oxidative decarboxylation of pyruvic acid. To sum up, the 1^st stage is ended by formation of acetylCoA which goes to Crebs cycle (2^nd stage)

Crebs stage occurs in mitochondrions. Its summary is: acetylCoA 3 NADH2+FPH2+ATP+2CO2.

This process includes the following reactions:

1. AcetylCoA+oxaloacetic acidcitric acid (citratesynthase)

2. Citric acid – H2O cys-aconitic acid

3. Cys-aconitic acid+H2Oisocitric acid

4. Isocitric acid+NADalfa-ketoglutaric acid+NADH2+CO2 (isocitrate dehydrogenase)

5. alfa-ketoglutaric acid+NAD+HSCoAsuccinylCoA+CO2+NADH2 (alfa-ketoglutarate dehydrogenase, alfa-ketoglutarate decarboxylase, acetyltransferase)

6. succinylCoA+GDPsuccinic acid+ATP+HSCoA (substrate phosphorylation)

7. succinic acid+FADfumaric acid+FADH2 (succinate dehydrogenase)

8. fumaric acid+H2Omalate (fumarase, or fumarate dehydrase)

9. malate+NADoxaloacetic acid+NADH2 (malate dehydrogenase)

Amphibolic (metabolic) role of the citric acid cycle (CAC):

1. oxidation of acetylS-CoA. This substance is produced in the body from metabolism of glucose and fatty acids. It is oxidized to CO2 and H2O in the CAC followed by the electron transport chain. Energy is also liberated – the total energy of 1 mole of acetylS-CoA is 209 kcals of which 96 kcals are utilized in the synthesis of 12 ATP molecules. The represents an efficiency of about 45%.

2. Integration with aminoacid (aa) metabolism. Many aa after being deaminated give rise to compounds that are also intermediate metabolites in CAC. F.e., 1) aspartic acid gives rise to oxaloacetic acid; 2) methionine, threonine and valine give rise to succinylS-CoA; 3) proline, histidine and arginine give rise to alfa-ketoglutaric acid.

3. Integration with fat metabolism. Fatty acids are also oxidized to acetylS-CoA which is also oxidized in the CAC. Moreover, fatty acids containing number of atoms produce propionylS-CoA. It is changed to methyl-malonyl-S-CoA which gives rise to succinyl-S-CoA that enter citric acid cycle.

4. Biosynthetic function. Several intermediates of this cycle take part in the formation of substances of great physiologic importance: a) citrate is provided to the lens of the eye, bone and the semina, plasma; b) succinyl-S-CoA is utilized in the synthesis of porphyrins needed for Hb formation; c) acetyl-S-CoA is used in the synthesis of cholesterol, fatty acids, acetylcholine ect. It also inactivates several drugs by acetylating them; d) α-ketoglutarate and oxaloacetate can undergo transamination, forming glutamic acid and aspartic respectively which are aminoacids.

5. Special role of CO₂ . It is produced in this cycle used in urea synthesis, though to a negligible extent.

6. CAC takes part in gluconeogenesis: oxaloacetate + GTP phosphoenolpyruvate + CO2 + GDP. Enzyme – phosphoenolpyruvate carboxykinase.

7. CAC takes part in the synthesis of nonessential aminoacids: aspartate + pyruvate ↔ oxaloacetate + alanine; glutamate + pyruvate ↔ α-ketoglutarate + alanine

8. CAC takes part in the synthesis of fatty acids: citrate + ATP + CoA-SH  acetyl-S-CoA + oxaloacetate + ADP + Pi. CAC can make 1 turnover without oxygen but for the following turnovers require oxygen for oxidation of NADPH2 and FPH2. The level of ATP regulate the rate of CAC. Excess of ATP leads to inhibition of CAC and accelerates the synthesis of fatty acids.

Biologic oxidation and oxidative phosphorylation.

The processes of oxidation are essential for maintaining life because oxidation and the simultaneously occurring reduction supply the free energy for the vital work. Originally oxidation was described as combination with oxygen but this definition has been radically changed. At present all reactions in which a molecule combines with oxygen or hydroxyl or loses hydrogen or electron are termed oxidative reactions. Because oxidation is always accompanied by reduction, therefore reduction will be represented by loss of oxygen or hydroxyl or gain of hydrogen or electron.

Only mitochondria can conduct the respiratory processes of the cell. The mitochondria contains all the enzymes involved in fatty acid oxidation and citric acid cycle: they also have been shown to contain what are termed electron transport particles which contain all the component concerned with electron transport in a regular sequence. In the last step of oxidation within cells H2O is formed. The mitochondria are therefore concerned with cellular respiration along with which ATP is formed (oxidative phosphorylation). For this reason the mitochondria have been called power-house of the cell. Mitochondria also contains the enzyme systems responsible for producing most of the reducing equivalents in the first place – the enzymes of β-oxidation and of the CAC. The latter is the final common metabolic pathway for the oxidation of all the major foodstuffs.

The major components of the respiratory chain are arranged sequentially in order of increasing redox potential.