I. Glycolysis- CytoplasmA. Overview1. Glucosea) Hexokinase- control the flow of carbon by alternating the Km- modified by +/- modulators to control the flow2. G-6-P3. F-6-Pa) Phosphofructokinase4. F-1,6-BP5. 13-PGP6. PEPa) Pyruvate kinase7. PyruvateB. Control of Glycolysis1. Hexokinase regulatory ligands (Kinase is talking about movement of protons):a) glucose-6-P - negative modulator, product that inhibits itselfb) G-6-P feeds back to the enzyme and is a negative modulator, slowing the reaction2. PFK- has a number of modulatorsa) ATP- (negative modulator) if have plenty of ATP in the cell, do not need it to be activeb) AMP- (positive modulator) means that ATP concentration is decreasing, so it is a positive modulator for the enzyme to make more ATPc) G-6-P – (positive modulator) will feed forward to make sure that this gets going, helping glycolysis to move alongd) citrate- (negative modulator ) *first compound in the Krebs Cycle, therefore downstream – if accumulates downstream, will feedback and tell this enzyme to make lesse) F-2,6-BP (postitive modulator- only a modulator not used for anything else)- this molecule is produced by F-6-P by the enzyme Phosphofructokinase-2 and is an incredible positive modulator- moves as fast as possible. G-6-P will turn on the phosphofructase 2 to turn on that enzyme to make more F-2,6-BP3. Pyruvate Kinasea) ATP- negative modulator- have plenty of ATP, doesn’t need to be activeb) F-1,6-BP- feed forward positive modulator- upstream, tells glycolysis to speed upc) Alanine- negative modulator from Protein breakdown, if you have this, you will not have to break down glucose for energy.II. Gluconeogenesis- slightly different path of pyruvate back to glucose- highly costlyIII. Pyruvate moved into the mitochondria (pre Krebs cycle)A. Pyruvate transported into mitochondria with 3 carbons and binds to pyruvate dehydrogenase (means electrons are getting transferred)1. Important to note: PDH has multiple peptides- many active sites, multiple regulatory sitesB. Reaction:1. Pyruvate (3C) + NAD + CoA (B-vitamin complex)  Acetyl CoA (2C with high energy bond) + NADH +CO2 (first step where we produce CO2)2. first reaction that consumes pyruvateIV. Krebs Cycle or TCA cycle or Citric acid Cycle (founded with radio-tracers)A. Acetyl-CoA (2C) converted to citrate (6C) with the intermediate oxaloacetate (4C)- oxaloacetate is always in excess1. this reaction is controlled by enzyme= citrate synthase (the PFK of Krebs)B. 7 reactions in Cycle1. Citrate (6C) (combination of oxoacetate and Aceyl CoA)  isocitrate (6C)2. Isocitrate (6C) --> alphaketoglutarate (5C)a) CO2 released hereb) Isocitrate dehydrogenase (IDH) – pair of electrons is moved from isocitrate to NAD to form NADH3. Alphaketoglutanate (5C)  Succinyl- Coa (4C)a) Co2 released here (two came in and 2 left .. these carbons are now the carbons from oxaloacetate, pyruvate is now gone)b) enzyme adds CoA to the carbon chainc) Alphaketoglutodehydrogenase (alphaKGDH)- takes electrons from alphaketogluterate and added to NAD to make NADH4. Succinyl CoA (4C)  Succinate (4C)a) An enzyme causes the release of the CoA and provides GDP with energy to make GTP and is stored in GTP5. Succinate  Fumaratea) Succinate dehydrogenase (SDH)- takes electrons from Succinate and makes Flavoadeninedinucleotide FADH2 from FAD6. Fumarate  Malate (4C)7. Malate  Oxaloacetate (4C)a) Malate dehydrogenase (MDH)- takes electrons from malate and makes NADH from NADC. Control points1. Isocitrate dehydrogenase (IDH)a) ADP- positive modulator- means do not have enough ATP so have to speed it up2. Malate dehydrogenase (MDH)a) ATP- negative modulator3. Citrate synthasea) Succinyl CoA- negative modulator for citrate synthaseD. Products1. 1 GTP, 3 NADH, 1 FADH2 for every one pyruvateE. Pathway stays the same for energy production from fatty acids and proteins1. Fatty acid- chopped to 2 carbon units that can be made into Acetyl CoA for Krebs Cyclea) Process: called Beta oxidationb) fatty acid + enzyme: Beta-oxidase  2 carbon units that added to vitamin CoA make Acetyl CoA2. Protein- every amino acid can be taken apart my dehydrogenase and converted to a different compound of the krebs cycle, some can come in as malate, alophaketoglutarate, succinyl etc.BY 330 1st Edition Lecture 7 Outline of Last Lecture B. 2nd law of thermodynamicsC. Control of Energy in GlycolysisD. Energy change in cellsOutline of Current Lecture I. GlycolysisA. OverviewB. Control of GlycolysisII. GluconeogenesisIII. Pyruvate into MitochondriaA. Pyruvate is transported into Mitochondria as 3 carbon unitB. ReactionIV. Krebs CycleA. Acetyl CoA converted to citrateB. 7 reactions in the cycleC. Control pointsD. ProductsE. Pathways remain the same for Fatty acid and Protein energy productionCurrent LectureI. Glycolysis- CytoplasmA. Overview1. GlucoseThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.a) Hexokinase- control the flow of carbon by alternating the Km- modified by +/- modulators to control the flow2. G-6-P 3. F-6-P a) Phosphofructokinase4. F-1,6-BP 5. 13-PGP6. PEPa) Pyruvate kinase7. Pyruvate B. Control of Glycolysis1. Hexokinase regulatory ligands (Kinase is talking about movement of protons):a) glucose-6-P - negative modulator, product that inhibits itselfb) G-6-P feeds back to the enzyme and is a negative modulator, slowing the reaction2. PFK- has a number of modulators a) ATP- (negative modulator) if have plenty of ATP in the cell, do not need it to be activeb) AMP- (positive modulator) means that ATP concentration is decreasing, so it is a positive modulator for the enzyme to make more ATPc) G-6-P – (positive modulator) will feed forward to make sure that this gets going, helping glycolysis to move alongd) citrate- (negative modulator ) *first compound in the Krebs Cycle, therefore downstream – if accumulates downstream, will feedback and tell this enzyme to make lesse) F-2,6-BP (postitive modulator- only a modulator not used for anything else)- this molecule is produced by F-6-P by the enzyme Phosphofructokinase-2 and is an incredible positive modulator- moves as fast as possible. G-6-P will turn on the phosphofructase 2 to turn on that enzyme to make more F-2,6-BP3. Pyruvate Kinase a) ATP- negative modulator- have plenty of ATP, doesn’t need to be activeb) F-1,6-BP- feed forward positive modulator- upstream, tells