AN INTRODUCTION TO METABOLISM

1. CHAPTER 8 AN INTRODUCTION TO METABOLISM

2. METABOLISM • TOTALITY OF AN ORGANISM’S CHEMICAL PROCESSES • METABOLIC PATHWAYS ARE GENERALLY OF TWO TYPES: • 1) CATABOLIC PATHWAYS-release of energy;breaking down molecules • 2) ANABOLIC PATHWAYS- using energy;building molecules

3. ORGANISMS TRANSFORM ENERGY • ENERGY- capacity to do work • KINETIC ENERGY- energy of motion • POTENTIAL ENERGY - stored energy (as in the bonds in a molecule) • ***energy can be transformed from one form to another

4. ENERGY TRANSFORMATIONS: LAWS OF THERMODYNAMICS • THERMODYNAMICS - STUDY OF ENERGY TRANSFORMATIONS • FIRST LAW = ENERGY CAN BE TRANSFERRED AND TRANSFORMED, BUT IT CANNOT BE CREATED OR DESTROYED • 2ND LAW = EVERY ENERGY TRANSFER MAKES THE UNIVERSE MORE DISORDED • ENTROPY - MEASURE OF DISORDER THAT IS PROPORTIONAL TO RANDOMNESS (S)

5. ENERGY SYSTEMS • CLOSED SYSTEM = COLLECTION OF MATTER UNDER STUDY WHICH IS ISOLATED FROM ITS SURROUNDINGS • OPEN SYSTEM = SYSTEM IN WHICH ENERGY CAN BE TRANSFERRED BETWEEN THE SYSTEM AND ITS SURROUNDINGS

6. COMBINING THE FIRST AND 2ND LAW OF THERMODYNAMICS • THE QUANTITY OF ENERGY IN THE UNIVERSE IS CONSTANT, BUT ITS QUALITY IS NOT • ALSO, ENERGY CAN BE TRANSFORMED, BUT PART OF IT IS DISSIPATED AS HEAT, WHICH IS LARGELY UNAVAILABLE TO DO WORK

7. FREE ENERGY: NECESSARY FOR SPONTANEOUS CHANGE • FREE ENERGY (G): AMOUNT OF ENERGY THAT IS AVAILABLE TO DO WORK; IT IS RELATED TO A SYSTEMS’ TOTAL ENERGY (H) AND ENTROPY (S) G = H - TS G = FREE ENERGY H = ENTHALPY OR TOTAL ENERGY T = TEMPERATURE IN °K S = ENTROPY

8. HOW ENERGY IS HARVESTED • THE MAXIMUM AMOUNT OF USABLE ENRGY THAT CAN BE HARVESTED FROM A REACTION IS THE SYSTEM’S FREE ENERGY CHANGE FROM THE INITIAL TO FINAL STATE • DG = D H - TDS • DG = change in free energy • D H = change in total energy • DS = change in entropy • T = absolute temp in °K

9. THE RELATIONSHIP OF FREE ENERGY TO STABILITY

10. FREE ENERGY VIDEO

11. DH = CHANGE IN ENTHALPY • DURING A CHEMICAL REACTION, REACTANT MOLECULES MUST ABSORB ENERGY FOR THEIR BONDS TO BREAK, AND ENERGY IS RELEASED WHEN BONDS FORM. • THE NET ENERGY CONSUMED OR RELEASED WHEN REACTANTS ARE CONVERTED TO PRODUCTS IS THE NET DIFFERENCE BETWEEN THE ENERGY CONSUMED AND RELEASED • **READ PAGE 91

12. “THE BONDS OF REACTANTS BREAK ONLY WHEN THE MOLECULES HAVE ABSORBED ENOUGH ENERGY TO BECOME UNSTABLE. (RECALL THAT SYSTEMS RICH IN FREE ENERGY ARE INTRINSICALLY UNSTABLE, AND UNSTABLE SYSTEMS ARE REACTIVE.) THE ACTIVATION ENERGY IS REPRESENTED BY THE UPHILL PORTION OF THE GRAPH, WITH THE FREE-ENERGY CONTENT OF THE REACTANTS INCREASING. THE ABSORPTION OF THERMAL ENERGY INCREASES THE SPEED OF THE REACTANTS, SO THEY

13. ARE COLLIDING MORE OFTEN AND MORE FORCEFULLY. ALSO, THERMAL AGITATION OF THE ATOMS IN THE MOLECULES MAKES THE BONDS MORE LIKELY TO BREAK. AT THE SUMMIT, THE REACTANTS ARE IN AN UNSTABLE CONDITION KNOW AS THE TRANSITION STATE; THEY ARE PRIMED, AND THE REACTION CAN OCCUR. AS THE MOLECULES SETTLE INTO THEIR NEW BONDING ARRANGEMENTS, ENERGY IS RELEASED TO THE SURROUNDINGS. THIS PHASE OF THE REACTION CORRESPONDS TO THE DOWNHILL PART

14. OF THE CURVE, WHICH INDICATES A LOSS OF FREE ENERGY BY THE MOLECULES. THE DIFFERENCE IN THE FREE ENERGY OF THE PRODUCTS AND REACTANTS IS DG FOR THE OVERALL REACTION, WHICH IS NEGATIVE FOR AN EXERGONIC REACTION.” • PAGE 91, BIOLOGY: 5TH EDITION

15. SIGNIFICANCE OF FREE ENERGY • INDICATES THE MAXIMUM AMOUNT OF A SYSTEM’S ENERGY WHICH IS AVAILABLE TO DO WORK • INDICATES WHETHER A REACTION WILL OCCUR SPONTANEOUSLY OR NOT • A SPONTANEOUS REACTION WILL OCCUR WITHOUT ADDITIONAL ENERGY

16. FREE ENERGY AND EQUILIBRIUM • AS A REACTION APPROACHES EQUILIBRIUM, THE FREE ENERGY OF THE SYSTEM DECREASES • WHEN A REACTION IS PUSHED AWAY FROM EQUILIBRIUM, THE FREE ENERGY INCREASES • WHEN A REACTION REACHES EQUILIBRIUM, DG = 0, BECAUSE THERE IS NO NET CHANGE IN THE SYSTEM

17. FREE ENERGY AND METABOLISM • EXERGONIC REACTIONS - NET LOSS OF FREE ENERGY • ENDERGONIC REACTIONS - NET GAIN OF FREE ENERGY • **IF A CHEMICAL PROCESS IS EXERGONIC, THE REVERSE PROCESS MUST BE ENDERGONIC

18. METABOLIC DISEQUILIBRIUM

19. ENERGY UNITS • JOULE IS THE METRIC UNIT OF ENERGY • JOULE (J) = 0.239 cal • KILOJOULE (kJ) = 1000 J OR 0.239 kcal • CALORIE (cal) = 4.184 J

20. ATP powers cellular work by coupling exergonic and endergonic reactions • ATP IS THE IMMEDIATE SOURCE OF ENERGY THAT DRIVES MOST RXNS INCLUDING: -MECHANICAL WORK (CILIA, MUSCLE CONTRACTION, MITOSIS) -TRANSPORT ( PUMPING IONS ACROSS CELL MEMBRANE) -CHEMICAL WORK - ENDERGOINC PROCESS OF POLYMERIZATION

21. ATP • A NUCLEOTIDE WITH UNSTABLE PHOSPHATE BONDS THAT THE CELL HYDROLYZES FOR ENERGY TO DRIVE REACTIONS WHAT IS ATP MADE OF???

22. HOW ATP PERFORMS WORK:THE MOLECULE ACQUIRING THE PHOSPHATE BECOMES MORE REACTIVE

23. THE ATP/ADP CYCLE

24. THE REGENERATION OF ATP • ATP IS CONTINUALLY REGENERATED BY THE CELL • PROCESS IS RAPID (107 MOLECULES USED AND REGENERATE/SEC/CELL) • REACTION IS ENDERGONIC • ADP + P >>> ATP DG = +31KJ/MOL • THE ENERGY TO DRIVE THE ENDERGONIC REGENERATIO OF ATP COMES FROM THE EXERGONIC PROCESS OF CELL RESPIRATION

25. ENZYMES • ENZYMES SPEED UP METABOLIC REACTIONS BY LOWERING ENERGY BARRIERS • FREE ENERGY CHANGE INDICATES WHETHER A REACTION WILL OCCUR SPONTANEOUSLY

26. ENZYMES • A CHEMICAL REACTION WILL OCCUR SPONTANEOUSLY IF IT RELEASES FREE ENERGY (-DG), BUT MAY BE TOO SLOW FOR LIVING CELLS • BIOCHEMICAL REACTIONS REQUIRE ENZYMES TO SPEED UP AND CONTROL REACTION RATES

27. ENZYME TERMS • CATALYST - ACCELERATES A REACTION WITHOUT BEING PERMANENTLY CHANGED IN THE PROCESS, SO IT CAN BE REUSED • ENZYMES-BIOLOGICAL CATALYSTS MADE OF PROTEIN • ACTIVATION ENERGY-AMT. OF ENERGY THAT REACTANT MOLECUES MUST ABSORB TO START A REACTION (EA) • TRANSITION STATE-UNSTABLE CONDITION OF REACTANT MOLECULES THAT HAVE ABSORBED SUFFICIENT FREE ENERGY TO REACT

28. ENERGY PROFILE OF AN EXERGONIC REACTION • REACTANTS MUST ABSORB ENERGY (EA) TO REACH TRANS. STATE 2) REACTION OCCURS AND ENERGY IS RELEASED AS NEW BONDS FORM 3) DG FOR REACTION IS DIFF. IN FREE ENERGY BTW. PRODUCTS AND REACTANTS

29. WHAT ARE ENZYMES??? • IN ORDER TO MAKE MOLECULES REACTIVE WHEN NECESSARY, CELLS USE CATALYSTS CALLED ENZYMES WHICH: • ARE PROTEINS • LOWER EA, SO THE TRANSITION STATE CAN BE REACHED AT CELL TEMPS. • DO NOT CHANGE THE NATURE OF THE REACTION, ONLY SPEED IT UP

30. ENZYME VIDEO

31. ENZYMES LOWER THE BARRIER OF ACTIVATION ENERGY

32. ENZYMES ARE SUBSTRATE SPECIFIC • ENZYMES ARE SPECIFIC FOR A PARTICULAR SUBSTRATE, AND THAT SPECIFICITY DEPENDS UPON THE ENZYME’S 3-D SHAPE • SUBSTRATE-THE SUBSTANCE AN ENZYME ACTS ON AND MAKES MORE REACTIVE

33. HOW ENZYMES WORK • AN ENZYME BINDS TO ITS SUBSTRATE AND CATALYZES ITS CONVERSION TO PRODUCT. THE ENZYME IS RELEASED IN ORIGINAL FORM • THE SUBSTRATE BINDS TO THE ENZYME’S ACTIVE SITE • SUBSTRATE + ENZYME >> ENZYME-SUBSTRATE COMPLEX >> PRODUCT + ENZYME

34. THE ACTIVE SITE • THIS IS A RESTRICTED REGION OF AN ENZYME MOLECULE WHICH BINDS TO THE SUBSTRATE • IS USUALLY A POCKET OR GROOVE • FORMED WITH ONLY A FEW OF THE ENZYME’S AMINO ACIDS • DETERMINES ENZYME SPECIFITY • CHANGES SHAPE IN RESPONSE TO THE SUBSTRATE • INDUCEDFIT = CHANGE IN SHAPE OF ACTIVE SITE, WHICH IS INDUCED BY THE SUBSTRATE

35. THE CATALYTIC CYCLE OF AN ENZYME

36. IMPORTANT ENZYME FACTS • 1) ENZYMES ARE UNCHANGED DURING REACTION • 2) ACTIVE SITE CAN HOLD TWO OR MORE REACTANTS SO THEY MAY REACT • 3) ACTIVE SITE’S MAY CHANGE SUBSTRATE TO HELP REACTIONS • 4) SIDE CHAINS OF AMINO ACIDS IN THE ACTIVE SITE MAY HELP IN REACTION

37. SUBSTRATE CONCENTRATIONS • THE HIGHER THE SUBSTRATE CONCENTRATION, THE FASTER THE REACTION-UP TO A LIMIT • ENZYME CAN BECOME SATURATED WITH SUBSTRATE(ACTIVE SITES OF ALL ENZYMES ARE ENGAGED) • THE REACTION RATE DEPENDS UPON HOW FAST THE ACTIVE SITES CAN CONVERT SUBSTRATE TO PRODUCT • MORE ENZYMES CAN BE ADDED TO INCREASE REACTION RATE

38. OPTIMIZING ENZYME ACTIVITY • EACH ENZYME HAS OPTIMAL ENVIRONMENTAL CONDITONS THAT FAVOR THE MOST ACTIVE ENZYME CONFORMATION

39. EFFECTS OF TEMPERATURE • OPTIMAL TEMPERATURE ALLOWS THE GREATEST NUMBER OF MOLECULAR COLLISIONS WITHOUT DENATURING THE ENZYME • Reaction rate increases as temp. increases. • Kinetic energy of reactant molecules increases • Optimal temp. range of most human enzymes is 35°-40° C • Excessive heat disrupts weak bonds

40. EFFECTS OF pH • OPTIMAL pH RANGE FOR MOST ENZYMES IS pH 6-8 • SOME ENZYMES OPERATE BEST AT MORE EXTREMES OF pH • EX: PEPSIN, A DIGESTIVE ENZYME FOUND IN THE STOMACH HAS AN OPTIMAL pH OF 2

41. TEMPERATURE AND pH

42. COFACTORS • COFACTORS ARE SMALL NONPROTEIN MOLECULES THAT ARE REQUIRED FOR PROPER ENZYME CATALYSIS • MAY BIND TIGHTLY TO ACTIVE SITE • MAY BIND LOOSELY TO BOTH ACTIVE SITE AND SUBSTRATE • SOME ARE INORGANIC (METAL ATOMS OF ZINC, IRON OR COPPER • SOME ARE ORGANIC AND ARE CALLED COENZYMES

43. ENZYMEINHIBITORS • CERTAIN CHEMICALS CAN SELECTIVELY INHIBIT ENZYME ACTIVITY • INHIBITION MAY BE IRREVERSIBLE IF THE INHIBITOR ATTACHES BY COVALENT BONDS • INHIBITION MAY BE REVERSIBLE IF THE INHIBITOR ATTACHES BY WEAK BONDS

44. COMPETITIVE INHIBITORS • CHEMICALS THAT RESEMBLE AN ENZYME’S NORMAL SUBSTRATE AND COMPETE WITH IT FOR THE ACITVE SITE • BLOCK ACTIVE SITE FROM THE SUBSTRATE • IF REVERSIBLE, THE EFFECT OF THE INHIBITORS CAN BE OVERCOME BY INCREASED SUBSTRATE CONCENTRATION

45. NONCOMPETITIVE INHIBITORS • INHIBITORS THAT DO NOT ENTER THE ENZYME’S ACTIVE SITE, BUT BIND TO ANOTHER PART OF THE ENZYME MOLECULE • CAUSE ENZYME TO CHANGE ITS SHAPE SO THE ACTIVE SITE CANNOT BIND SUBSTRATE • MAY ACT AS METABOLIC POISONS (DDT, MANY ANTIBIOTICS)

46. ENZYME INHIBITION

47. ALLOSTERIC REGULATION • SPECIFIC RECEPTOR SITE ON SOME PART OF THE ENZYME MOLECULE OTHER THAN THE ACTIVE SITE • MOST ENZYMES WITH ALLOSTERIC SITES HAVE TWO OR MORE POLYPEPTIDE CHAINS, EACH WITH ITS OWN ACTIVE SITE. ALLOSTERIC SITE ARE OFTEN LOCATED WHERE THE SUBUNITS JOIN

48. ALLOSTERIC REGULATION

49. COOPERATIVITY • SUBSTRATE MOLECULE THEMSELVES MAY ENHANCE ENZYME ACTIVITY • COOPERATIVITY= SUBSTRATE BINDING TO THE ACTIVE SITE OF ONE SUBUNIT INDUCES CONFORMATIONAL CHANGE THAT HELPS SUBSTRATE BINDING AT THE ACTIVE SITES OF THE OTHER SUBUNITS

50. COOPERATIVITY