BISC330L Lecture 23 Intro to Metabolism Chapter 15 BISC330L 2nd half metabolism BISC 330L BIOCHEMISTRY USC SPRING 2014 NEW VERSION Metabolism The focus for the remainder of the course will be on metabolism and we will seek an answer to the following quesPon How does a cell extract energy from its environment Fact a hummingbird can store enough energy in its body to y 500 miles between meals Why do we need energy to perform mechanical work muscle contracGon cellular movement acGve transport of molecules and ions across biological membranes synthesis of macromolecules from simple precursors How do we get energy animals plants How do we get energy Glucose metabolism Chapter 16 How do we get energy The Citric Acid Cycle Chapter 17 How do we get energy OxidaGve phosphorylaGon Chapter 18 How do we get energy animals plants ATP How do we get energy Photosynthesis Chapter 19 How do we get energy The Calvin Cycle Chapter 20 How do we get energy 1 2 3 5 ATP 4 ATP Metabolism The number of life sustaining chemical reacGons that occur within cells is vast 1000 even for a simple E coli bacterial cell Metabolism Many many reacGons Common moGfs that make the process as a whole understandable Common moGfs in metabolism A universal currency for energy ATP metabolic reacGons Two general classes those that convert energy from fuel into useful forms CATABOLIC fuel carbohydrates fats those that require energy in order to proceed ANABOLIC CO2 H2O energy energy simple precursor complex molecules metabolic reacGons ReacGon coupling allows thermodynamically unfavorable reacGons to be driven by favorable reacGons recall G H system T S system Ch 1 G GO RT x ln C D A B Ch 8 metabolic reacGons For coupled reacGons the overall free energy change is an addiGve property example A B A B C D GO 21 kJ mol GO 34 kJ mol C D GO 13 kJ mol Coupled reacGons and ATP hydrolysis triphosphate adenine ribose ATP H2O ATP H2O ADP Pi G0 30 5 kJ mol AMP PPi G0 45 6 kJ mol ATP hydrolysis drives metabolic reacGons A B A ATP H2O GO 16 7 kJ mol K eq B A 10 G0 5 69 1 15 x 10 3 B ADP Pi GO 13 8 kJ mol K eq 2 67 x 102 By coupling the conversion of A to B w ATP hydrolysis the equilibrium raGo of B to A changes by a factor of 105 allowing the reacGon to proceed Why is ATP such an e cient phosphoryl group donor ATP H2O ADP Pi G0 30 5 kJ mol 1 Resonance stabilizaPon orthophosphate Pi has a number of resonance forms of similar energy ATP has a very limited number of resonance forms of similar energy structure shows an unfavorable example Why is ATP such an e cient phosphoryl group donor ATP H2O ADP Pi G0 30 5 kJ mol 2 ElectrostaPc repulsion At pH 7 ATP s triphosphate unit carries 4 negaPve charges in close proximity Repulsion is reduced when ATP is hydrolyzed Why is ATP such an e cient phosphoryl group donor ATP H2O ADP Pi G0 30 5 kJ mol 3 StabilizaPon due to hydraPon Water binds more e ciently to ADP and Pi than it does ATP Other biological phosphoryl group donors Other biological phosphoryl group donors Molecules with greater phosphoryl transfer potenPal than ATP can be used to convert ADP to ATP through phosphorylaPon CreaGne phosphate enables strenuous exercise creaGne phosphate ADP ATP creaGne GO 12 6 kJ mol ATP uGlizaGon during strenuous exercise Cellular NTPs are interconvertable kinase NDP ADP nucleoside monophosphate Some other NTPs GTP UTP CTP NMP ATP NDP ATP nucleoside diphosphate NTP ADP kinase note that these reacPons are readily reversible and that the direcPon is dictated by the concentraPons of the reactants this means that GTP can be converted to ATP readily and this becomes important later when we visit the citric acid cycle ATP is the primary donor of free energy for metabolic and other biochemical reacPons ATP turnover is very high in the body each molecule lasts about a minute before being consumed The total amount in the body is 100 grams however strenuous exercise consumes 500 grams minute ATP regeneraPon must therefore be highly e cient ATP regeneraPon Carbon containing fuel molecules like glucose or fats are oxidized to CO2 and the energy released is used to convert ADP and Pi to ATP OxidaGon of carbon fuels OxidaPon of carbon containing fuels drives ATP regeneraPon The more reduced the carbon group is the more energy released during oxidaPon OxidaGon of carbon fuels Fuel molecules are complex but oxidaPon takes place one carbon at a Pme Q which is the bejer fuel Carbon compound oxidaGon releases energy Shown is the net reacPon for oxidaPon of GAP to 3 phosphoglyceric acid to see how ATP is generated we need to look at the complete 2 step reacPon Step 1 carbon oxidaPon generates an acyl phosphate group with electron transfer to NAD to form NADH NADH will be discussed later Other biological phosphoryl group donors The reacPon product from step 1 1 3 BPG has very high phosphoryl transfer potenPal Step 2 Cleavage of 1 3 BPG is then coupled to synthesis of ATP from ADP Key point the energy of oxida on is rst trapped in a high phosphoryl transfer compound and then used to form ATP This is called substrate level phosphoryla on OxidaGon of carbon fuels also generates ATP through the formaGon of ion gradients Also a 2 step process 80 of ATP is generated in this manner oxidaPve phosphorylaPon Ch 18 Energy from food is extracted in three stages Stage 1 Large complex molecules are processed into usable units Fats are broken down to fajy acids and glycerol Polysaccharides are processed to glucose and other simpler sugars Proteins are hydrolyzed to amino acids No energy is generated here This is Diges on Energy from food is extracted in three stages Stage 2 Numerous small carbon compounds are degraded to a common end product acetyl CoA Some energy ATP is generated in this step but some is also consumed as we will see Energy from food is extracted in three stages Stage 3 The acetyl group of acetyl CoA is completely oxidized to CO2 Electrons are released captured by intermediates NAD and FAD and used to power a proton gradient that synthesizes ATP Common moGfs in metabolism Limited number of acGvated intermediates The kinds of reacGons involved is small Regulatory mechanisms are highly conserved across all forms of life AcGvated intermediates in metabolism ATP NADH and NADPH FADH2 Acetyl CoA Electron acceptors NAD and NADP Structure adenosine like molecules containing an addiPonal ribose group and a reacPve group reacPve group nicoPnamide ring which is synthesized from the vitamin niacin NAD NADP R H R PO3 2 Electron acceptor NAD