Assistant professor of Biochemistry By Dr. Manal Louis Assistant professor of Biochemistry

By the end of this lecture, the student should be able to: Identify the energetics of chemical reactions. Determine the concept of free energy change and high energy compounds. Recall the sources of ATP and their role in ATP cycle.

Bioenergetics Bioenergetics is the study of energy changes accompanying biochemical reactions

Free energy and free energy change Free energy (G): It is an amount of energy capable of doing work during a reaction. (Gibbs free energy) Free-energy change (DG): is a measure of the chemical energy available from a reaction DG = G products - G reactants

DGo = standard free energy change (at 1M conc of reactants & products) DGo' = standard free energy change at pH 7.

Energetics of Chemical Reactions

The difference is given up as heat or work Releases energy The difference is given up as heat or work

- DG = a spontaneous reaction. When a reaction proceeds with release of free energy, the free energy change has a negative value and the reaction is called Exergonic - DG = a spontaneous reaction. Thermodynamically favorable reactions Physiological unidirectional mainly catabolic pathways A B ADP+Pi ATP

Needs energy

Opposite is Endergonic reaction in which there is gain of free energy. +DG = the reaction is not spontaneous and needs the provision of energy. They are thermodynamically unfavorable reactions. Mainly anabolic reactions. B A ADP + Pi ATP

If DG = ZERO the reaction is in equilibrium In this case forward and backward reactions are running in equal speed. A B

Exergonic Reaction Endergonic Reaction Vs Exergonic Endergonic Exergonic Reaction Endergonic Reaction Spontaneous Not Spontaneous Release Free Energy ( -ΔG) Consume Free Energy (+ΔG) Products have less energy than reactants Products have more energy than reactants

Coupling between exergonic and endergonic

Chemical Structure of ATP ATP is a nucleoside triphosphate which contains: Adenine Ribose Three phosphate Groups Adenine Base 3 Phosphates - - - Ribose Sugar

It functions as Mg complex

It is the energy currency of the cell. What Does ATP Do for You? It supplies YOU with ENERGY! It is the energy currency of the cell.

How Do We Get Energy From ATP? By breaking the high- energy bonds between the last two phosphates in ATP On hydrolysis of the terminal phosphate ∆G= -7.3 Kcal/mol

Group Transfer Potential Is the free energy change ∆G that occurs upon transfer of a particular group from a donor molecule to an accepting molecule.

= P Group Transfer Potential High energy Compounds ∆G Kcal/mol Phosphoenol pyruvate -14.8 Carbamoyl phosphate -12.3 1,3 Bisphosphoglycerate -11.8 Creatine phosphate -10.3 ATP ADP + Pi -7.3 ADP AMP + Pi -6.6 Pyrophosphate Glucose-1-phosphate -5.0 = P Group Transfer Potential

NB CoA (acetyl CoA, succinyl CoA) Acetyl lipoamide High energy compounds are not necessarily phosphate-containing. Thiol ester involving: CoA (acetyl CoA, succinyl CoA) S-adenosyl methionine SAM Acetyl lipoamide

Since the concentration of ATP is very small and meets the needs of the body for few seconds, ATP is continuously consumed and regenerated at a very high rate. The ADP-ATP Cycle phosphate removed

A- Phosphorylation at the substrate level The ADP-ATP Cycle A- Phosphorylation at the substrate level ATP is formed by high energy phosphate from compounds higher in the table to ADP In glycolysis: catalyzed by phosphoglyceric kinase and pyruvate kinase.

In TCA cycle: catalyzed by succinate thiokinase.

Creatine phosphate cycle When ATP is plenty skeletal muscles cardiac muscles brain Spermatozoa build high concentration of creatine phosphate (muscle contraction)

Interconversion of adenine nucleotides: Adenylate Kinase ATP + AMP 2 ADP

B- Oxidative phosphorylation This is the greatest source of ATP in aerobic organism. The free energy needed to form ATP is derived from oxidation of the reducing equivalents.

Overview of catabolism FATS POLYSACCHARIDES PROTEINS Stage 1 fatty acids, glycerol glucose, other sugars amino acids Stage 2 acetyl CoA CoA H2O O2 Overview of catabolism, source of all the erengy is what we will spend a lot of time at. ATP synthesis down here, process by which most ATP is made is oxidative phosphorylation, if we go to the top of this we can see the source of the ultimately making ATP are common everyday substances found in the diet that we need to take in in order to sustain life. Three categories of substances provide most of the energy and lots of other things that we need. You see catabolism as a multistage process, first takes macromolecules, breaks them down into smaller ones like these, not a process that yields any energy directly, but sets stage for later catabolism. See from this arrangement that the process of catabolism is a convergent one. Even though this one is simplified, lots of different things are metabolized in such a way to produce a few smaller molecules, this one showing acetyl co A that was derived from the carbons of all three of these, and then by a cycle known as Krebs cycle, a final common pathway, substances which do produce electrons feed into there and that is where ATP is actually made. This overview is something to come back to during the course of this quarter because we will in turn take up the metabolism of carbohydrates, central section here, and get all the way through here, section 5 and 6, in the next section, lipid metabolism, and amino acid metabolism, and nucleotides later on. This is one of the several kind of overview slides that should be used to organize. Stage 3 e– CO2 Krebs cycle oxidative phosphorylation v v ATP ADP + Pi 14

QUESTIONS The standard free energy of hydrolysis of terminal phosphate group of ATP is (A) –7,3 Kcal/mol (B) –8,3 Kcal/mol (C) 10 Kcal/mol (D) +7,3 Kcal/mol

Two examples of substrate level phosphorylation in glucose metabolism are: (A) 1,3 bisphosphoglycerate and phosphoenolpyruvate. (B) Glucose-6 phosphate and Fructo-6-phosphate. (C) 3 phosphoglyceraldehyde and phosphoenolpyruvate. (D) 1,3 diphosphoglycerate and 2-phosphoglycerate.