MCS Metabolism Class Notes

1. what is metabolism: - chemical processes that occur within a living organism in order to maintain life - reactions that turn food into energy 2. what are the four essential macromolecules and what are they broken down into: - proteins -> amino acids - fats -> fatty acids - carbohydrates -> glucose - nucleic acids -> nucleotides 3. how are the 4 macromolecules obtained: - through food - we break down food during digestion into components that make up the macromolecules 4. what is metabolism the balance of: - the balance of breakdown and building up of macromolecules 5. what is catabolism: - breaking down of molecules for energy 6. what is anabolism: - building up of molecules - required energy - come from the food we eat (glucose) - cellular respiration 7. what regulates catabolism and anabolism: - hormones 8. explain the steps of glycolysis: 1. glucose phosphorylated using ATP which releases ADP. forms glucose 6 phosphate (G6P). is a irreversible reaction catalysed by hexokinase 2. G6P is converted to fructose 6 phosphate in a reversible reaction 3. F6P is phosphorylated using ATP which releases ADP. forms fructose 1,6 bisphosphate. catalysed by phosphofructokinase 4. F1,6BP undergoes series of reversible reactions to form Phosphoenolpyruvic acid (PEP) 5. PEP is irreversible converted to pyruvate. catalysed by pyruvate kinase. ADp takes a phosphate to release ATP 9. what are the reactions that form PEP from F1,6BP: 1. F1,6BP reversible converts to DHAP(dihydroxyacetone phosphate) and G3P (glyceraldehyde 3-phosphate) [DHAP and G3P also reversible convert to each other 2. G3P irreversibly converts to 1,3 BPG (1,3 bisphosphoglycerate) 3. 1,3BPG reversibly converts to 3PG (3,phosphoglyceric acid) 4. 3PG reversibly converts to 2PG (same) 1/5 5. 2PG reversible converts to PEP 10. What are the products of glycolysis: - 2 pyruvate - 2 ATP - 2 NADH 11. why does glycolysis need to be regulated: - when cells lack energy -> glycolysis needs to be increased - when cells have lots of energy -> glycolysis needs to be reduced - when blood glucose level high -> glycolysis needs to be increased - when blood glucose level high -> glycolysis needs to be reduced 12. what reactions control regulation in glycolysis: - the ones with irreversible reaction - conversion of glucose to G6P - conversion of F6P to F1,6Bp - conversion of 2 PEP to 2 pyruvate 13. explain hexokinase inhibition in the glycolytic pathway: - inhibited by G6P - high concs of G6P signal that cell no longer need glucose so glucose will be left in the blood - glucokinase (in liver) is not inhibited by G6P but it phosphorylates glucose when it is abundant - glucokinase provides G6P for synthesis of glycogen (storage form of glucose) 14. explain the inhibition of phosphofructokinase in the glycolytic pathway: is inhibited allosterically - high conc of ATP lower its affinity for fructose 6 phosphate - AMP overcomes the inhibitory action of ATP so the activity of phosphofructokinase increases when the ATP/AMP ratio is lowered 15. explain the inhibition of pyruvate kinase in the glycolytic pathway: - the L-type isozyme of pyruvate kinase found in liver and M type in muscle and brain are activated by F1,6BP to enable them to process incoming high concs of intermediates in the glycolytic pathway - ATP allosterically inhibits L and M to slow down glycolysis when the energy charge is high - alanine allosterically inhibits pyruvate kinases to signal that building blocks are abundant 16. what is beriberi: - neurological and cardiovascular disorder caused by a dietary deficiency of thiamine (vitamine B1) - the levels of pyruvate and alpha-ketoglutarate in the blood are higher than normally especially after ingestion of glucose 2/5 - causes: alcohol abuse, xtreme nausea/vomiting in pregnancy, people with AIDS, after bariatric surgery 17. Where does the Krebs cycle occur?: mitochondrial matrix 18. explain the steps of the krebs cycle: 1. pyruvate is oxidised to Acetyl-COa using pyruvate dehydrogenase complex 2. acetyl-coa reacts with oxaloacetate to form citrate (6c) catalysed by citrate synthase 3. citrate is isomerised into isocitrate using aconitase enzyme 4. isocitrate is oxidised to alpha-ketoglutarate using isocitrate dehydrogenase. Nad is reduced to NADH and CO2 is released 5. alpha-ketoglutarate is converted into succinyl COa using alpha-ketoglutarate dehydrogenase. NAD is reduced to NADH. CO2 is released 6. succinyl COa is converted into succinate by succinyl COa synthase. GTP is released 7. succinate is converted into fumarase using succinate dehydrogenase. FADH2 is released 8. fumarase is converted into malate using fumarase enzyme 9. malate is converted into oxaloacetate by malate dehydrogenase. NAD is reduced to NADH 19. what are the two main regulators of the krebs cycle: - allosteric enzymes - isocitrate dehydrogenase - alpha-ketoglutarate dehydrogenase 20. explain isocitrate dehydrogenase regulation of krebs cycle: - is allosterically stimulated by ADP, this enhanced the enzymes affinity for substances - NADH inhibits isocitrate dehydrogenase by displacing NAD+ - ATP inhibits isocitrate dehydrogenase 21. explain alpha-ketoglutarate dehydrogenase regulation of krebs cycle: alpha-ketoglutarate dehydrogenase is inhibited by its catalytic products: succinyl COa and NADH - alpha-ketoglutarate dehydrogenase is inhibited by a high energy charge. so, the rate of the krebs cycle is reduced when the cell has a high conc of ATP 22. Mitochondria structure: outer membrane intermembrane space folded inner membrane matrix 3/5 23. give the overall steps of the electron transport chain: 1. inner membrane contains 4 sets of enzyme complexes 2. NADH and FADH2 from krebs cycle donate electrons to the enzyme complexes and the electrons travel from the first complex to the fourth 3. movement of electron generates energy 4. this energy is used to pump H+ ions into the intermembrane space from the matrix of the mitochondria 5. the continuous pumping of H+ causes the generation of a higher conc of H+ in intermembrane space vs the matrix. this makes the intermembrane space positively charged and matrix negatively. electrochemical gradient 6. the H+ can't cross into matrix as inner membrane of mitochondria is not permeable to ions 7. ATP synthase is used as a transporter and transports H+ into matrix 8. the flow of H+ is used to phosphorylate ADP to ATP 24. explain the 1st complex in the ETC: - is NADH dehydrogenase complex -is an L shaped protein complex - one arm of the L is in the intermembrane space and the other is in the matrix - this complex removes hydrogen from NADH - and receives electrons from NADH and transports it further along the chain 25. explain the second complex in the ETC: - is succinate dehydrogenase complex - removes hydrogen from succinate forming fumarase (krebs cycle) - FADH2 is produced which is used to donate electrons to the chain 26. explain the third complex in the ETC: - is cytochrome reductase - cytochromes are proteins which have haems as prosthetic grps with iron core - the complex contains cytochromes B, C1 and C - role: accepts electrons and transports them to cytochrome C - cytochrome C then transports electrons to complex 4 27. explain the 4th complex in the ETC: - is cytochrome C oxidase - haem and copper containing complex - receives electrons from cytochrome C and uses the electrons for the reduction of O2 to H2O 28. how many H+ are pumped from NADH and FADH2 in the ETC: - electrons from NADH pump 3 H+ into intermembrane space therefore can make 3 ATP - FADH2 makes 2 ATP 29. explain the ATP synthase structure: - consists of two multi-subunit components: Fo and F1, which are linked by a stalk 4/5 - Fo spans the lipid bilayer, forming a channel through which protons can cross the membrane - F1 collects the free energy derived from proton movement down the electrochemical gradient by catalysing the synthesis of ATP 30. explain the regulation of the ETC: - regulated by phosphorylation - conc of ADP determines the rate of oxidative phosphorylation - unless ADP is phosphorylated to ATP, electrons don't flow through ETC to O2 - oxidative phosphorylation is coupled to the consumption of ATP 5/5