Introduction to metabolism

Introduction to metabolism following the curriculum of medical biochemistry of MBBS course

1. INTRODUCTION TO METABOLISM Dr. Farhana Atia Associate Professor Department of Biochemistry Nilphamari Medical College, Nilphamari

2. Metabolism Metabolism is the term refers to all chemical reactions that occur in the living cells catalyzed by enzymes, coenzymes, cofactors & regulated by hormones, vitamins Aim Release energy from ingested food Transformation of small organic compound into macromolecule

3. Pathways of Metabolism Pathways of metabolism- Anabolic pathways Catabolic pathways Amphibolic pathways

4. Anabolism Involves in the biosynthesis of larger and more complex molecules from smaller precursors & requires expenditure of energy either in the form of ATP or using reducing equivalents storing NADH/ NADPH Involves in the breakdown of larger molecules like glucose, amino acid, FA & form CO₂, H₂O, NH₃ & energy. commonly involving oxidative reactions; they are exothermic, producing reducing equivalents and ATP(mainly via the respiratory chain). Catabolism

5. Amphibolic pathway occur at the ‘crossroads’ of metabolism, acting as links between the anabolic and catabolic pathways can be either anabolic or catabolic, depending on the energy conditions in the cell

6. Conversion of food energy to ATP

7. Bioenergetics Study of energy changes associated with biochemical reaction. Free energy [G]: Energy available to do work. Standard free energy change [∆G⁰] Exergonic /energy yielding reaction catabolism reaction proceed spontaneously with loss of free energy [∆G negative] Endergonic /energy requiring reaction reaction proceed only if free energy is gained [∆G negative] Coupled with exergonic reaction

8. Transfer of energy Biological system use chemical energy to maintain living process Free energy is obtained by breakdown of complex organic molecules Much of liberated energy is not used directly by the cell But there is a formation of bond between phosphoric acid residue & certain organic compounds Different amount of energy is released on hydrolysis of the bond

9. ATP ATP plays a central role in transfer of free energy The standard free energy [∆G⁰] on hydrolysis of terminal phosphate of ATP is -7.3 kcal/mol This value divides the biochemically important phosphates into 2 groups Low energy phosphates : have G⁰ value smaller than that of ATP. High energy phosphates : G⁰ value is higher than that of ATP. It include ATP.

10. High & Low Energy Phosphate Compounds Compound ∆G⁰ (Kcal/mol) Phosphoenolpyruvate -14.8 Carbamoyl phosphate -12.3 1,3-Bisphosphoglycerate -11.8 Creatine phosphate -10.3 ATP AMP+PPi -7.7 ATP ADP+Pi -7.3 Glucose-1-phosphate -5.0 PPi -4.6 Fructose-6-phosphate -3.8 Glucose-6-phosphate -3.3 Glycerol-3-phosphate -2.2

11. ATP: Energy carrier ATP is able to act as a donor of high energy phosphate [~P ] to form low energy phosphate compounds Likewise, ADP can accept ~P to form ATP Thus ATP/ADP cycle connects those process that generate ~P to those processes that utilize ~P

12. Biologic oxidation Oxidation [removal of electron or H] of biomolecules within biologic system Oxidation is always accompanied by reduction of an electron acceptor Can take place without participation of molecular oxygen [dehydrogenation]

13. Redox potential It is the numerical expression of free energy change during oxidation-reduction. It is the tendency of any redox pair to lose or gain electron [quantitatively expressed as E0 with unit in volt ] More negative RP  tendency to lose electron More positive RP  tendency to accept electron H⁺/H₂ -0.42v NAD⁺/NADH -0.32v FMN/FMNH₂ -0.22v

14. Respiratory Chain Highly organized chain of enzyme & coenzyme in mitochondria Arranged in order of increasing redox potential Collect & transport reducing equivalents (H/electron)

15. Respiratory Chain In respiratory chain biomolecule become oxidized & coenzyme reduced Reduced coenzyme then deliver 2H to RC through which H propagate, sequentially reduce & oxidize every component of chain finally get condensed with molecular oxygen to form H₂O, and the liberated free energy is trapped as ATP (in the machinery for oxidative phosphorylation).

16. Respiratory Chain

17. Component of respiratory chain Four large protein complexes embedded in inner mitochondrial membrane Complex I : NADH-Q oxidoreductase Complex III : Q- cytochrome c oxidoreductase Complex IV : cytochrome c oxidase Complex II : Succinate-Q reductase (some substrate use it instead of complex I) Other component Flavoproteins (I & II) Iron-Sulfur proteins /Fe-S (I, II & III)

18. Reaction in Respiratory Chain Salient feature Substrate: Reduced coenzyme Product: ATP, H₂O Site: All cells with mitochondria Compartment: Inner mitochondria Nature: Catabolic

19. Conversion of food energy to ATP

20. Electron Flow Trough Respiratory Chain

21. Inhibitors of RC Site of inhibition Barbiturates Complex I by blocking the transfer from Fe-S to Q Antimycin A Dimercaprol Complex III H₂S Carbon monoxide Cyanide Complex IV & totally arrest respiration Malonate Competitive inhibitor of complex II Oligomycin Flow of protons through ATP synthase Uncouplers :- 2,4-dinitrophenol Thermogenin Dissociates oxidation in respiratory chain from phosphorylation

22. Phosphorylation Addition of phosphate group to an acceptor molecule by high/ low energy phosphate bond to capture the energy produced during catabolism. 2 types

23. Oxidative phosphorylation Flow of electron through respiratory chain generates ATP by a process called oxidative phosphorylation . Oxidation of reduced coenzyme & phosphorylation of ADP are coupled H+ transport results in an electrochemical gradient Proton motive force : energy released by flow of H + down its gradient is used for ATP synthesis ATP synthase : H + channel that couples energy from H + flow with ATP synthesis

24. Use of ATP Synthetic reaction Muscle contraction Nerve conduction Active transport

25. Phosphorylation at substrate level ATP can also be formed in some situation when free energy is released by a chemical reaction. This is phosphorylation at substrate level. 1,3-DPG 3-DPG ADP ATP

26. Compartments of different metabolic pathway Cytosol Mitochondria Endoplasmic reticulum Glycolysis TCA cycle Protein synthesis HMP shunt RC Oxidative phosphorylation Cholesterol synthesis Glycogenesis β -oxidation Glycogenolysis Ketogenesis Lipogenesis Deamination Transamination Gluconeogenesis Urea cycle Heme synthesis

27. Thank You