An introduction to metabolism

1. An introduction to metabolism

2. An introduction to metabolism Totality of an organisms chemical reactions

3. An introduction to metabolism Totality of an organisms chemical reactions The chemical factory

4. Key concepts • An organism’s metabolism transforms matter and energy, according to the laws of thermodynamics • The free energy change of a reaction tells us whether the reaction occurs spontaneously • ATP powers cellular work by coupling endergonic and exergonic reactions • Enzymes speed up chemical reactions • Regulation of enzyme activity helps control metabolism

5. Matter review • Something that has mass and occupies space • Matter consists of atoms that are bound together to form molecules • Atoms are never created or destroyed in biological systems (Conservation of matter) but molecules can be

6. Energy review • Definition: Energy is the ability to do work • First law of thermodynamics: Energy cannot be created or destroyed but, it can be converted to other forms • Forms Potential: stored energy Kinetic: energy in motion

7. Energy review • Definition: Energy is the ability to do work • First law of thermodynamics: Energy cannot be created or destroyed but, it can be converted to other forms • Forms Chemical energy Kinetic

8. Energy review • Definition: Energy is the ability to do work • First law of thermodynamics: Energy cannot be created or destroyed but, it can be converted to other forms • Forms Heat and light Chemical energy

9. Energy review • Definition: Energy is the ability to do work • First law of thermodynamics: Energy cannot be created or destroyed but, it can be converted to other forms • Second law of thermodynamics: • Some energy becomes unusable with every energy transfer • Another way to state this: every energy transfer increases entropy (a measure of disorder and randomness) • I.e. hot pan and cold sink

10. What does this have to do with metabolism?

11. Metabolism Metabolism involves metabolic pathways that change in matter and energy Begin with a specific molecule which is then altered in a series of defined steps. Each step is catalyzed by an enzyme.

12. Metabolism Metabolism involves metabolic pathways that change in matter and energy • Anabolic pathways build complicated molecules from simple molecules. They consume energy! • Catabolic pathways breakdown molecules. They release energy!

13. An organism’s metabolism transforms matter and energy, according to the laws of thermodynamics

14. The free energy change of a reaction tells us whether the reaction occurs spontaneously

15. The free energy change of a reaction tells us whether the reaction occurs spontaneously The energy available to do work

16. The free energy change of a reaction tells us whether the reaction occurs spontaneously This means that the reaction does not require energy…it doesn’t necessarily happen fast though.

17. Free energy change • Unstable systems have a high G, stable systems have a low G All systems will go to a more stable state…unless something prevents this from happening

18. Free energy change • Unstable systems have a high G, stable systems have a low G All systems will go to a more stable state…unless something prevents this from happening

19. Free energy change All systems will go to a more stable state…unless something prevents this from happening • Unstable systems have a high G, stable systems have a low G • Change in free energy of a system is symbolized by ∆G • ∆G=G final state - G initial state • The ∆G is negative when the process involves a loss of free energy. This occurs spontaneously. Equilibrium is the maximum stability

20. Reactants Amount of energy released (∆G < 0) Energy Free energy Products Progress of the reaction (a) Exergonic reaction: energy released Products Amount of energy required (∆G > 0) Energy Free energy Reactants Progress of the reaction (b) Endergonic reaction: energy required Free energy change and chemical reactions • Exergonic reaction • Proceeds with a net release of energy • ∆G is negative • Occurs spontaneously • Endergonic reaction • Absorb free energy • ∆G is positive • Not spontaneous (requires energy)

21. The free energy change of a reaction tells us whether the reaction occurs spontaneously

22. ATP powers cellular work by coupling exergonic and endergonic reactions

23. Types of cellular work • Chemical work (pushing of endergonic reactions) • Transport work • Mechanical work

24. Types of cellular work • Chemical work (pushing of endergonic reactions) • Transport work • Mechanical work Cells accomplish all of these things by energy coupling- using an exergonic reaction to drive an endergonic one • ATP is usually involved • Adenine triphosphate • Contains a ribose sugar, adenosine, and three phosphate groups • Bonds with phosphate groups can be broken to release energy (generates ADP + Pi)

25. How ATP performs chemical work NH2 ∆G = +3.4 kcal/mol NH3 + Glu Glu Typically ATP aids in the driving endergonic chemical reactions through phosphorylation • Transfers a phosphate group to the reactant • Reactant becomes unstable • Reactant reacts forming a new product Glutamic acid Glutamine Ammonia ATP phosphorylates glutamic acid, making the amino acid less stable. P 1 ADP ATP + + Glu Glu NH2 Ammonia displaces the phosphate group, forming glutamine. P NH3 P + + i Glu Glu

26. Membrane protein P P i Solute transported Solute (a) Transport work: ATP phosphorylates transport proteins ADP + ATP P i Vesicle Cytoskeletal track ATP Protein moved Motor protein (b) Mechanical work: ATP binds noncovalently to motor proteins, then is hydrolyzed How ATP performs transport and mechanical work

27. ATP + H2O Energy for cellular work (endergonic, energy-consuming processes) Energy from catabolism (exergonic, energy-releasing processes) ADP P + i Regeneration of ATP

28. ATP powers cellular work by coupling exergonic and endergonic reactions

29. Enzymes speed up metabolic reactions by lowering energy barriers

30. Enzymes speed up metabolic reactions by lowering energy barriers A macromolecule, typically a protein, that speeds up a chemical reaction without being used up

31. Activation energy • All chemical reactions involve bond formation and breaking • Bonds need to be in an unstable (high free energy state) to change • An initial investment in energy is required to destabilize bonds • New bonds formed will be more stable (energy is released)

32. Activation energy Even in exergonic reactions, activation energy is a barrier A B C D Transition state EA A B C D Reactants Free energy A B ∆G < O C D Products Progress of the reaction

33. 2 Substrates Enzyme-substrate complex Enzyme Products How do enzymes function? • Substrate binds to the enzyme’s active site • Substrate specificity is based on protein shape • While they are bound the enzyme converts the reactant to the product • After the product is created, the enzyme releases it and can catalyze another reaction • Most metabolic reactions are reversible, the same enzyme can catalyze the reverse reaction

34. 2 Substrates Enzyme-substrate complex Enzyme Products How does this interaction speed up the rate of a chemical reaction? • Enzymes orient reactants properly for the reaction to occur • Enzymes can stretch the substrate (causing unstable bonds) • Enzymes can create micro environments • The active site can participate directly in the chemical reaction

35. Optimal temperature for typical human enzyme Optimal temperature for enzyme of thermophilic (heat-tolerant) bacteria Rate of reaction 40 0 60 100 20 80 Temperature (ºC) (a) Optimal temperature for two enzymes Optimal pH for trypsin (intestinal enzyme) Optimal pH for pepsin (stomach enzyme) Rate of reaction 4 5 6 7 8 9 10 0 1 2 3 pH (b) Optimal pH for two enzymes Remember, proteins are sensitive to environmental conditions

36. What other factors impact enzyme function? Cofactors-non-protein helpers aid catalytic activity • If organic called a coenzyme i.e. Catalase, an antioxidant that neutralizes free radicals in the cell, contains an iron atom which aids in bringing the substrate to the transition state

37. Substrate Active site Competitive inhibitor Enzyme Noncompetitive inhibitor (c) Noncompetitive inhibition (b) Competitive inhibition (a) Normal binding What other factors impact enzyme function? Inhibitors • Competitive inhibitors bind to the enzyme’s active site • Non-competitive inhibitors bind elsewhere on the molecule, but change the shape of the active site • Can be reversible or irreversible (impacts can very)

38. Enzymes speed up metabolic reactions by lowering energy barriers

39. Regulation of enzyme activity helps control metabolism

40. Regulation of enzyme activity helps control metabolism • Allosteric • Cooperativity • Positive and negative feedbacks

41. Active site (one of four) Allosteric enyzme with four subunits Regulatory site (one of four) Activator Active form Stabilized active form Oscillation Non- functional active site Inhibitor Inactive form Stabilized inactive form (a) Allosteric activators and inhibitors Substrate Stabilized active form Inactive form (b) Cooperativity: another type of allosteric activation Regulation of enzyme activity helps control metabolism Cells can regulate biochemical pathways by • Making more or less of an enzyme • Regulating enzyme function • Cooperativity • Substrate bind to the active site of one subunit of a multi sub-unit enzyme • Amplifies the catalytic response • Allosteric regulation • similar to non-competitive inhibition (molecules bind at an allosteric site to alter the shape of the active site) • Can inhibit or stimulate enzyme function

42. Regulation of enzyme activity helps control metabolism A Negative feedback  Enzyme 1 Feedback regulation B D Enzyme 2 Excess D blocks a step D D C Enzyme 3 D (a) Negative feedback W Enzyme 4 X Positive feedback + Enzyme 5 Excess Z stimulates a step Z Y Z Z Enzyme 6 Z (b) Positive feedback

43. Regulation of enzyme activity helps control metabolism

44. Key concepts • An organism’s metabolism transforms matter and energy, according to the laws of thermodynamics • The free energy change of a reaction tells us whether the reaction occurs spontaneously • ATP powers cellular work by coupling endergonic and exergonic reactions • Enzymes speed up chemical reactions • Regulation of enzyme activity helps control metabolism

45. Concept map Cohesion Water High specific heat Hydrogen bonds

46. Concept map Water forms Hydrogen bonds give water special properties including High specific heat Cohesion

47. Metabolism concept map cell Exergonic Enzyme inhibitor Metabolism Chemical reaction Catabolic Metabolic pathway Enzymes ATP Allosteric Metabolic regulation Cooperativity Feedback anabolic Endergonic