Krebs Cycle

• In 1937, Sir Hans Krebs, discovered series of metabolic reactions that became known as Krebs Cycle. He received the Nobel Prize in 1953 for this important discovery 

• Fritz Albert Lipmann shared the Nobel Prize with Krebs for his discovery of coenzyme A and the key role it plays in metabolism

• Krebs cycle is a cyclic series of reactions that transfer energy from organic molecules to ATP, NADH, and FADH2 and removes carbon atoms as CO2
• Krebs cycle is an eight-step process, each step catalyzed by a specific enzyme.

• Krebs cycle is a cyclic process because oxaloacetate, product of step eight is the reactant in step one.
• The overall chemical equation for Krebs cycle is:

oxaloacetate+acetyl-CoA+ADP+Pi+3NAD+FAD---->

CoA+ATP+3NADH+3H+FADH2+CO2

• The Krebs cycle begins as acetyl-CoA condenses with oxaloacetate to form citrate. 

• In glycolysis, glucose is broken down into two pyruvate molecules. 2-carbon fragment of pyruvate is used in making acetyl-CoA. Acetyl-CoA enters the kreb cycle, which takes place in mitochondrion.
• In the process of converting pyruvate into acetyl-CoA, CO2 is produced and a molecule of NADH is formed.
• The acetyl group (2-C) of acetyl-CoA is transferred to a 4-C molecule, which will produce 6-C compound. CoA is released.
• The 6-C molecule is then converted into a 5-C compound by loosing CO2 and 2 H atoms that reduce NAD+ to NADH.
• Oxidation and decarboxylation occurs. NADH and CO2 are produced. ATP is produced as well. As a result of these reactions, 4-C molecule is formed
• 4-C molecule is further oxidized and hydrogens that were removed are used in making NADH and FADH2. These reactions regenerate the 4-C molecule that reacted with acetyl-CoA.
• By the end of Krebs cycle the glucose molecule is entirely consumed. The 6-C atoms leave the process as 6 low energy CO2 molecules, which are released as wastes.
• In one turn of the cycle, the last 2-C atoms of the original glucose molecule are removed as CO2 , and free energy is transferred to ATP, NADH and  FADH2
• All that is preserved of the original glucose molecule is mostof its energy which is stored as: 4 ATP molecules (2 from glycolysis and 2 from Krebs cycle) and 12 reduced coenzymes ( 2 NADH from glycolysis, 2 NADH from pyruvate oxidation, 6 NADH from Krebs cycle and 2 FADH2 from the Krebs cycle)
• Free energy stored in NADH and FADH2 will eventually be transferred to ATP in the last stage of cellular respiration, called the electron transport and chemiosmosis
• The Krebs cycle occurs twice for each molecule of glucose processed, since 2 molecules of acetyl-CoA are formed from one molecule of glucose
• By the end of Krebs cycle, all 6-C atoms of glucose have been oxidized to CO2 and released from the cell as metabolic waste
• The reduced coenzymes, NADH and FADH2 now go on to the next process, electron transport and chemiosmosis, where their free energy will be transferred to ATP

Metabolism and Laws of Thermodynamics

First law of thermodynamics
(conservation of mass, energy), states that energy  cannot be created or destroyed, however it can be transformed or transferred. For example, when we light a match we're not creating energy but we're changing the form of energy. So when the match is burning, potential energy is converted into heat and light energy.

Energy In -- Energy Out = Energy Change 

In the case of human body energy in is the calories from food and energy out is comprised of basal metabolic rate and exercise. Energy change is the accumulation or loss of either fat or muscle. If energy in is greater than energy out, weight is gained. If energy out is greater than energy in, weight is lost.

Second law of thermodynamics
(entropy), explains the phenomenon of irreversibility in nature. This law states that the entropy of universe increases with any  change that occurs. For example, a new package of playing cards is highly ordered. If we throw the cards into the air, the cards get randomly assorted by the time they reach the ground---> entropy gets increases. Entropy is the measure of  randomness in energy or in objects. The universe favours an increase in entropy. In any closed area, the amount of entropy will tend to increase. The metabolism of a cell achieves this by coupling the spontaneous process of catabolism to the non spontaneous process of anabolism. Overall, in thermodynamic terms, metabolism maintains order by creating a disorder. All changes either directly or indirectly result in an increase in the entropy (overall disorder) of the universe.


Third law of thermodynamics
(Absolute Zero) ---> bottom point on the Kelvin temperature scale. The Kelvin scale is absolute, meaning 0 kelvin is mathematically the lowest possible temperature in the universe.This corresponds to about -273.15 Celcius. 

Getting back to normal body temperature from zero temperature would take days and even weeks. At absolute zero, some cells would start up again causing a malfunction in the body system since not all organs or not all cells would be functioning right away after the absolute zero temperature. Getting back to normal body temperature from zero temperature would take days and even weeks. At absolute zero, some cells would start up again causing a malfunction in the body system since not all organs or not all cells would be functioning right away after the absolute zero temperature.

Second Law of Thermodynamics + Metabolic Process

Although living organism's amazing complexity appears to contradict this law, life is possible as all organisms are open systems  that exchange matter as well as energy with their surroundings. Living systems are not in equilibrium, but instead systems maintain their high complexity by causing a larger increasing the entropy of their environment. The anabolic processes in the cell build highly  ordered structures such as proteins and DNA. By coupling free energy yielding catabolic processes with energy requiring anabolic processes, living things building up their bodies and world around them. They do this at the expense of the entropy of the universe as a whole. The entropy in a particular system, such as an organism, may decrease, so long as the total entropy of the system plus its surroundings increases. Thus organisms are islands of low entropy in an increasing random universe. Metabolism enables natural forms to persist in states that are far from equilibrium for extended periods. If the second law of thermodynamics describe the essential tendencies of nature, from largest to smallest  physical systems and spamming organic-inorganic divide the nature's essential activity would be metabolic.
 Living organisms obey the second law of thermodynamics. They create order out of chaos in the local area of universe at the expense of creating a greater amount of disorder in the universe as whole. The evolution of biological order is perfectly consistent with the laws of thermodynamics.