Cellular Metabolism

1. Cellular Metabolism • Energy as it relates to Biology • Metabolism • Catabolism (ATP production) • Glycolysis and the TCA Cycle • Anabolism (Synthetic pathways) • Protein Synthesis

2. Metabolism • Definition = “All chemical reactions that take place within an organism.” • Metabolic pathways = network of linked reactions • Basic feature: coupling of exergonic rxs with endergonic rxs. (direct vs. indirect coupling)

3. Review: • Energy = capacity to do work • Usually from ATP • Enzymes = biological catalyst • Lower activation energy • Return to original state • Opportunity for control

4. Metabolism Catabolism Energy Anabolism Synthesis Energy transferred commonly measured in calories: 1 cal =  1 g of H2O by 1° C 1 Kcal =  temp. of 1L H2O by 1o C. = Calorie (capital C) Energy released in catabolic reactions is trapped in 1) Phosphate bonds 2) Electrons

5. Metabolic pathways: Network of interconnected chemical reactions Linear pathway Intermediates Circular pathway Branched pathway

6. Control of Metabolic Pathways (Chapter 6) • Enzyme concentration (already covered) • Enzyme modulators - Feedback- or end product inhibition - Hormones - Other signaling molecules • Different enzymes for reversible reactions • Enzyme isolation • Energy availability (ratio of ADP to ATP)

7. Catabolic Pathways: ATP-Regeneration Amount of ATP produced reflects on usefulness of metabolic pathways: • Aerobic pathways • Anaerobic pathways Different biomolecules enter pathway at different points

8. ATP Cycle ATP = Energy Carrier of Cell (not very useful for energy storage) ATP : ADP ratio determines status of ATP synthesis reactions

9. Glycolysis • From 1 glucose (6 carbons) to 2 pyruvate (3 carbons) molecules • Main catabolic pathway of cytoplasm • Does not require O2  common for (an)aerobic catabolism • Starts with phosphorylation of Glucose to Glucose 6-P • (“Before doubling your money you first have to invest!”)

12. The Steps of Glycolysis Net gain?

13. Pyruvate has 2 Possible Fates: Anaerobic catabolism:Pyruvate Lactate Aerobic catabolism:Pyruvate Citric Acid Cycle

15. Intermediate Step

16. Glycolysis

18. Citric Acid Cycle Other names ? Takes place in ? Energy Produced: 1 ATP 3 NADH 1 FADH2 Waste – 2 CO2 Electron transport System

19. NADH NADH NADH FADH2 Energy Yield of Krebs Cycle

20. Final step:Electron Transport System • Chemiosmotic theory / oxidative phosphorylation • Transfers energy from NADH and FADH2 to ATP (via e- donation and H+ transport) • Mechanism:Energy released by movement of e- through transport system is stored temporarily in H+ gradient • NADH produces a maximum of 2.5 ATP FADH2 produces a maximum of 1.5 ATP • 1 ATP formed per 3H+ shuttled through ATP Synthase

21. Organelles

22. Electron Transport Chain • On the inner membrane of the mitochondria • Protein complexes including enzymes and iron-containing proteins called cytochromes • Chemiosmotic Theory • Movement of electrons through the etc to produce ATP

23. Steps to produce ATP • Pairs of high-energy electrons pass from complex to complex along the etc. • Energy released by these reactions is used to pump H+ from the mitochondrial matrix into the intermembrane space. • The movement of protons creates a concentration gradient • As the protons move down their concentration gradient into the matrix potential energy stored in the concentration gradient is transferred to the high –energy bond of ATP

24. Oxidative Phosphorylation • Oxygen is required as the final electron and proton acceptor

26. ATPsynthase • When the protons move back into the mitochondrial matrix through a pore in ATPsynthase stored energy is converted into chemical-bond energy • The ATPsynthase transfers KE to the high-energy phosphate bond of ATP • A portion of this energy transfer is released as heat and absorbed into the blood

29. Electron Transport Chain

35. Summary of CHO catabolism Cellular Respiration Maximum potential yield for aerobic glucose metabolism: 30-32 ATP synthesized from ADP H2O is a byproduct

36. Glycogen Synthesis Gluconeogenesis Made from glucose Stored in all cells but especially in • Liver (keeps 4h glycogen reserve for between meals) • Skeletal Muscle  muscle contraction Glycolysis in reverse From glycerol, aa and lactate All cells can make G-6-P, only liver and Kidney can make glucose

37. Water Soluble Vitamins • B1 (Thiamine) • Part of coenzyme cocarboxylase • Transformation of pyruvic acid to acetyl CoA • Deficits • Beriberi • Decreased appetite • Vision disturbances • Unsteady gait • Loss of memory and confusion • Fatigue • tachycardia

38. Water Soluble Vitamins • B2 (Riboflavin) • FAD and FMN • Hydrogen acceptors in body • Deficits • Cracking of lips • Tongue turns purple red and shiny • Light sensitivity • Decreased energy

39. Water Soluble Vitamins • B3 (Niacin) • Constituent of NAD • Deficits • Listlessness • Headache • Weight loss and loss of appetite • Sore red tongue and lips • Nausea • Vomiting • Diarrhea • Photosensitivity • Cracked and ulcerated skin

40. Water Soluble Vitamins • B6 (Pyridoxine) • Coenzyme pyridoxal phosphate • Functions in amino acid metabolism • Formation of antibodies and hemoglobin • Deficits • Increased risk of heart disease • Seborrhea around eyes and mouth • In infants: nervous irritability and convulsions

41. Water Soluble Vitamins • B5 (Pantothenic acid) • Coenzyme A • Deficits • Loss of appetite • Abdominal pain • Depression • Muscle spasms

42. Water Soluble Vitamins • Biotin • Coenzyme for Krebs cycle • Deficits • Scaly skin • Muscle pain • Pallor • Anorexia • Nausea • Fatigue • Elevated blood cholesterol

43. Water Soluble Vitamins • C (Ascorbic Acid) • Antioxidant • Formation of connective tissue • Converts tryptophan to serotonin • Enhances iron absorption • Deficits • Joint pains and poor both and tooth growth • Poor wound healing • scurvy

44. Water Soluble Vitamins • B12 (Cyanocobalamin) • Coenzyme in gastrointestinal cells, nervous tissue and bone marrow • Synthesis of DNA • Division of erythrocytes • Deficit • Pernicious Anemia • Pallor • Anorexia • Dyspnea • Weight loss

45. Water Soluble Vitamins • Folic Acid • Coenzymes for synthesis of methionine and other amino acids • DNA synthesis • Formation of red blood cells • Formation of normal neural tube in embryonic development • Deficits • Megaloblastic anemia • Gastrointestinal disturbances • Diarrhea • Spina bifida in new born • Low birth weight • Neurological deficits • Increased risk of heart attack and stroke

46. Fat Soluble Vitamins • A (Retinol) • Synthesis of photoreceptor pigments • Development of teeth and bone • Antioxidant • Deficits • Night blindness • Dry skin and hair • Dry eyes • Defects to developing embryo

47. Fat Soluble Vitamins • D (Antirachitic factor) • Functionally a hormone • Increases calcium in blood by enhancing absorption • Acts with PTH to remove calcium from bones • Assists in blood clotting mechanism • Deficits • Demineralization of bones and teeth • Rickets or osteomalacia • Restless muscle syndrome

48. Fat Soluble Vitamins • E (Antisterility factor) • Antioxidant for free radicals • Prevents oxidation of fatty acids and cholesterol • Prevents atherosclerosis • Deficits • Possible decrease in life span • K (Coagulation vitamin) • Formation of clotting proteins • Deficits • Easy bruising and prolonged bleeding

49. Protein Catabolism • Proteases • Peptidases • Deamination (removal of the NH3) • NH3 becomes urea • Pyruvate, Acetyl CoA, TCA intermediates are left.

50. Transamination