Other High Energy Compounds Examples of other high energy compounds Enol Phosphates: e.g: Phosphoenol pyruvate (PEP) is high energy phosphate, but for a completely different reason than ATP. - PEP is formed in the glycolytic pathway and is used to synthesize ATP from ADP. - PEP is formed in the glycolytic pathway and is used to synthesize ATP from ADP. - The reaction with ADP to form ATP is essentially irreversible. - The reaction with ADP to form ATP is essentially irreversible. Reasons: Enol form of pyruvic acid is less stable than the keto form by about kcal/mole. In addition an enol phosphate is less stable than any ordinary phosphate ester by about 3kcal/mole. The phosphate can only exist as the high energy enol form. Thus when phosphate group is removed, the pyruvate can go back to the stable low energy ket form and the surplus energy is released. Thiol esters e. g: Thioesters of coenzyme A as acetyl~Co A: - In this compound, there is a diminshed resonance interaction between electrons of the sulfur and the carbonyl group relative to the resonance in an oxygen ester. - In this compound, there is a diminshed resonance interaction between electrons of the sulfur and the carbonyl group relative to the resonance in an oxygen ester. -The sulfur will not form a double bond as readily as oxygen. -The sulfur will not form a double bond as readily as oxygen. Phosphocreatine ATP- PC system PC stored at the muscle It is one step reaction resulting in getting energy. The reaction catalyzed by creatine kinase enzyme. PC restoration only occurs during rest when ATP stores are high. Ingestion of creatine has been proven to help in performance in high intensity short term exercise. Creatine slows the fatigue process because during the rest stage there is larger amount of ATP replinshed compared to a person who is not taking creatine. Biosynthesis work as energy requiring process Biosynthesis is a programmed process that leads from very simple molecule to the living cell itself. The flow sheet of biosynthesis For the biosynthesis of cell components, two kinds of ingrediants are required. 1- precursors e.g C,H,N 1- precursors e.g C,H,N 2- ATP 2- ATP Degradative and synthetic pthways between two points given (e.g glucose and pyruvate are not identical (i.e they are not the simple reverse of each other). Degradation of one mole of glucose to pyruvate is accompanied by formation of 2 ATP whereas biosynthesis of glucose from pyruvate requires an input of total 6- high energy phosphate bond (4 ATP + 2GTP). i.e Both pathways vary in their energetics Both are independently regulated in the cell, while PFK is activated by AMP and inhibited by ATP, fructose 1,6 diphosphatase has AMP or ADP as negative modiulators. Terminal phosphate group of ATP is transferred to the building block molecule to be energized. This is known as orthophosphate cleavage. But sometimes a pyrophosphate group is used to activate the building blocks (Pyrophosphate cleavage, more energy 2x Kcal/mole. Channeling of high energy phosphate of ATP through other nucleotides Adenylate Energy Charge Some enzymes respond to absolute concentration, but most respond to ratios. Dan Atkinson introduced the concept of ENERGY CHARGE in 1968 to summarize the energy status of a cell. It is a measure of the relative concentration of high-energy phospho- anhydride bonds available in the adenylate pool. Some enzymes respond to absolute concentration, but most respond to ratios. Dan Atkinson introduced the concept of ENERGY CHARGE in 1968 to summarize the energy status of a cell. It is a measure of the relative concentration of high-energy phospho- anhydride bonds available in the adenylate pool. Defenition Of AEC AEC is defined as the effective mole fraction of ATP in the total adenylate pool (ATP, ADP, AMP). AEC is defined as the effective mole fraction of ATP in the total adenylate pool (ATP, ADP, AMP). The energy charge, or E.C., has the range 0 to 1.0. If all the adenylate is in the form of ATP, E.C. = 1.0, and the potential for phosphoryl transfer is maximal. The energy charge, or E.C., has the range 0 to 1.0. If all the adenylate is in the form of ATP, E.C. = 1.0, and the potential for phosphoryl transfer is maximal. At the other extreme, if AMP is the only adenylate form present, E.C. = 0. At the other extreme, if AMP is the only adenylate form present, E.C. = 0. Then the relative amounts of the three adenine nucleotides are fixed by the energy charge. The following figure shows the relative changes in the concentrations of the adenylates as energy charge varies from 0 to 1.0. Regulatory enzymes in energy-producing catabolic pathways show greater activity at low energy charge, but the activity falls off sharbly as E.C. approaches 1.0. In contrast, regulatory enzymes of anabolic sequences are not very active at low energy charge, but their activities increase as E.C. nears 1.0. These contrasting responses are termed R, for ATP-regenerating, and U, for ATP-utilizing. Regulatory enzymes such as PFK and pyrvuate kinase in glycolysis follow the R response curve as E.C. is varied. Note that PFK itself is an ATP-utilizing enzyme, using ATP to phosphorylate fructose- 6-phosphate to yield fructose-1,6- bisphosphate. Nevertheless, because PFK acts physiologically as the valve controlling the flux of carbohydrate down the catabolic pathways of cellular respiration that lead to ATP regeneration, it responds as an R enzyme to energy charge. Regulatory enzymes in anabolic pathways, such as acetyl-CoA carboxylase, which initiates fatty acid biosynthesis, respond as U enzymes. Regulatory enzymes in anabolic pathways, such as acetyl-CoA carboxylase, which initiates fatty acid biosynthesis, respond as U enzymes.