Introduction to Metabolism

1. Introduction to Metabolism

2. Metabolism • The sum of the chemical changes that convert nutrients into energy and the chemically complex products of cells • Hundreds of enzyme reactions organized into discrete pathways • Substrates are transformed to products via many specific intermediates • Metabolic maps portray the reactions

3. A Common Set of Pathways • Organisms show a marked similarity in their major metabolic pathways • Evidence that all life descended from a common ancestral form • There is also significant diversity • Autotrophs use CO2; Heterotrophs use organic carbon; Phototrophs use light; Chemotrophs use Glc, inorganics use S and obtain chem energy through food generated by phototrophs.

4. The Sun is Energy for Life • Phototrophs use light to drive synthesis of organic molecules • Heterotrophs use these as building blocks • CO2, O2, and H2O are recycled

6. Metabolism • Metabolism consists of catabolism and anabolism • Catabolism: degradative pathways • Usually energy-yielding! • “destructive metabolism” • FUELS -> -> CO2 + H2O + useful energy • Anabolism: biosynthetic pathways • energy-requiring! • “constructive metabolism” • Useful energy + small molecules --> complex molecules

8. Organization in Pathways • Pathways consist of sequential steps • The enzymes may be: • Separate • Form a multienzymecomplex • A membrane-bound system • New research indicates that multienzyme complexes are more common than once thought

10. Catabolism and Anabolism • Catabolic pathways converge to a few end products • Anabolic pathways diverge to synthesize many biomolecules • Some pathways serve both in catabolism and anabolism and are called amphibolicpathways

11. Digestion of food polymers: • enzyme-catalyzed hydrolysis • Glycolysis: • glucose catabolism • generate ATP without consuming oxygen (anaerobic) • Citric Acid Cycle: • metabolism of acetyl-CoA derived from pyruvate, fatty acids, and amino acids • acetyl oxidized to CO2 • operates under aerobic conditions • reduction of coenzymes NAD+ and FAD; energy used to produce ATP • Oxidative phosphorylation: • reduction of molecular oxygen by NADH and FADH2 • energy of reduced compounds used to pump protons across a cell membrane • potential energy of electrochemical gradient drives phosphorylation of ADP to ATP

12. Comparing Pathways • Anabolic & catabolic pathways involving the same product are not the same • Some steps may be common to both • Others must be different - to ensure that each pathway is spontaneous • This also allows regulation mechanisms to turn one pathway and the other off

15. METABOLIC REGULATION Regulated by controlling: • Amounts of enzymes • Catalytic activities • Accessibility of substrates

17. The ATP Cycle • ATP is the energy currency of cells • In phototrophs, light energy is transformed into the light energy of ATP • In heterotrophs, catabolism produces ATP, which drives activities of cells • ATP cycle carries energy from photosynthesis or catabolism to the energy-requiring processes of cells

20. Redox in Metabolism • NAD+ collects electrons released in catabolism • Catabolism is oxidative - substrates lose electrons, usually H- ions • Anabolism is reductive - NADPH provides the electrons for anabolic processes, and the substrates gain electrons

21. WHY ATP? • Free energy is released when ATP is hydrolyzed. • This energy drives reactions that need it (eg. muscle contraction) • Recall coupled reactions • ATP has a higher phosphoryl transfer potential

22. RECURRING MOTIFS IN METAB • Certain compounds keep on recurring or appearing in metabolic reactions and their functions are the same in the processes • Metab looks complicated but reactions are actually limited and repeating.

23. ACTIVATED CARRIERS • These species help carry out the metabolic reactions, even nonfavorable ones, at times • Example: ATP (activated carrier of phosphoryl groups)

24. Activated carriers of electrons for fuel oxidation: e- acceptors! • Aerobic systems: O2 is the final e- acceptor, but this does not occur directly • Fuels first transfer e- to carriers: pyridine molecules or flavins. NAD+: nicotinamide adenine dinucleotide

25. Activated carriers of electrons for fuel oxidation: e- acceptors! FAD: Flavin adenine dinucleotide

26. Activated carrier of electrons for reductive biosynthesis: e- donors! NADPH: common electron donor R is phosphate group

27. Activated carrier of two-carbon fragments COENZYME A: carrier of acyl groups

28. Activated carrier of two-carbon fragments

30. VITAMINS • Many vitamins are "coenzymes" - molecules that bring unusual chemistry to the enzyme active site • Vitamins and coenzymes are classified as "water-soluble" and "fat-soluble" • The water-soluble coenzymes exhibit the most interesting chemistry

34. Key Reactions in Metabolism

35. 1. REDOX reactions • Electron carriers are needed!

36. 2. LIGATION reactions • Bond formation facilitated by ATP cleavage

37. 3. ISOMERIZATION reactions

38. 4.GROUP TRANSFER

39. 5.HYDROLYTIC reactions • Bond cleavage by addition of H2O

40. 6.ADDITION of functional groups to double bonds or REMOVAL of groups to form double bonds • Uses lyases

41. GLYCOLYSIS

43. Glycolysis • 1897: Hans and Eduard Buchner (Sucrose cell-free experiments; fermentation can take place outside of living cells) METABOLISM became simple chemistry • Glycolysis: “Embden-Meyerhof pathway”

44. The all-important Glucose • The only fuel the brain uses in non-starvation conditions • The only fuel red blood cells can use • WHY? • Evolutionary: probably available for primitive systems

45. The products and their fates

46. Glycolysis • AKA Embden-Meyerhof-ParnasPathway • Involves the oxidation of glucose • Products: • 2 Pyruvate • 2 ATP • 2 NADH • Cytosolic

47. Glycolysis • Anaerobic • The entire process does not require O2

48. Glycolysis: General Functions • Provide energy in the form of ATP • Generate intermediates for other pathways: • Hexose monophosphate pathway • Glycogen synthesis • Pyruvate dehydrogenase • Fatty acid synthesis • Krebs’ Cycle • Glycerol-phosphate (TG synthesis)

49. Specific functions of glycolysis • Red blood cells (RBCs) • Rely exclusively for energy • Skeletal muscle • Source of energy during exercise, particularly high intensity exercise • Adipose tissue • Source of glycerol-P for TG synthesis • Source of acetyl-CoA for FA synthesis • Liver • Source of acetyl-CoA for FA synthesis • Source of glycerol-P for TG synthesis

50. Regulation of Cellular Glucose Uptake • Brain & RBC: • The GLUT-1 transporter has high affinity for glucose and is always saturated. • Ensures that brain and RBC always have glucose. • Liver: • The GLUT-2 glucose transporter has low affinity and high capacity. • Uses glucose when fed at rate proportional to glucose concentration • Muscle & Adipose: • The GLUT-4 transporter is sensitive to insulin