Download presentation
Presentation is loading. Please wait.
1
Chapter 11: Glycolysis -ose -ase
amylose sucrose lactose glucose fructose amylase -ose disaccharides -ase Active transport passive transport Low [Glc] High [Glc] Low [Glc] “Enjoy the chemical elegance of metabolism”
2
Chapter 11: Glycolysis Defined: Glucose is converted anaerobically to the three carbon acid pyruvate (only top half diagram) Net Reaction: Glucose + 2 ADP + 2 NAD+ + 2 Pi 2 Pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H2O 1-4 = hexose (6C) stage: 2 ATP’s consumed. 5-10 = triose 2(3C) stage: 4 ATP’s produced. Net: 2 ATP’s. Max energy when pyruvate from glycolysis enters Citric Acid Cycle Makes reducing eqivalents NADH and QH2 (FADH2)
3
Glyceraldehyde-3-phosphate dehydrogenase
Glucose ATP Phosphorylation Hexokinase The Pathway ADP Glucose-6-phosphate Isomerization Glucose-6-phosphate isomerase Fructose-6-phosphate ATP Phosphofructokinase-1 Phosphorylation ADP Fructose-1,6-bisphosphate Cleavage Aldolase Dihydroxyacetone phosphate Isomerization Trios phosphate isomerase Glyceraldehyde-3-phosphate Glyceraldehyde-3-phosphate NAD+ + Pi Glyceraldehyde-3-phosphate dehydrogenase NAD+ + Pi Oxidation and Phosphorylation NADH + H+ NADH + H+ 1,3-bisphosphoglycerate 1,3-bisphosphoglycerate ADP Substrate Level Phosphorylation Phosphoglycerate kinase ADP ATP ATP 3-phosphoglycerate 3-phosphoglycerate Phosphoglycerate mutase Rearrangement 2-phosphoglycerate 2-phosphoglycerate Enolase H2O H2O Dehydration phosphoenolpyruvate phosphoenolpyruvate ADP ADP ATP Pyruvate kinase Substrate Level Phosphorylation ATP pyruvate pyruvate
4
Glycolysis: Step 1, Hexokinase
I-III IV Isozymes Different inhibition profiles Location, Km Control point Can’t leave the cell
5
Glucose 6-Phosphate Isomerase
Glycolysis: Step 2 Glucose 6-Phosphate Isomerase Aldose Opens the chain during the rxn CH2OH Ketose OH Stereospecific: uses -Glc; produces -D-fructose-6-phosphate
6
Step 3, Phosphofructokinase-1
First COMMITted step of glycolysis -anomer PFK-1 Phosphofructokinase-1 Other 6-C sugars can enter and convert to fru-6-phos fructose, mannose, etc. Metabolically irreversible rxn. It is an allosteric enzyme and a REGULATory CONTROL step for glycolysis (AMP and citrate).
7
Glycolysis: Steps 2 and 3 Opens the chain during the rxn PFK-1
CH2OH OH utilizes 100% -anomer Stereospecific: uses -Glc; produces 100% -D-fructose-6-phosphate 36% -fructose % -fructose
8
Glycolysis: Step 4, Aldolase
Fig 11.5 Mech Rxn is near equilibrium, so not a control point Basic residue or metal withdraws an e- polarizing C2 carbonyl Basic residue removes a proton from the C4 hydroxyl group 1 2 3 4 5 6 Rapid depletion of 2 products in subsequent steps drives rxn
9
Step 5, Triose Phosphate Isomerase
Ketose Aldose near equil. Only G3P, not DHAP, can be utilized in step 6 Now have 2 molecules G3P for step 6 Consumption in step 6 maintains steady state conc. of G3P Ketose-aldose conversion is diffusion controlled After conversion, C-1=C-6, C-2=C-5, C-3=C4 (see textbook)
10
Step 5, Triose Phosphate Isomerase
Ketose Aldose near equil.
11
Glyceraldehyde 3-Phosphate Dehydrogenase
Glycolysis: Step 6 Glyceraldehyde 3-Phosphate Dehydrogenase from Pi Higher group transfer potential than ATP Oxidation has neg G, some energy conserved in acid anhydride linkage Oxidation is coupled to phosphorylation to conserve energy, instead of oxidation to free carbonic acid and energy loss
12
Step 7, Phosphoglycerate Kinase
First ATP generating step Substrate level phosphorylation- Nucleotide diphosphate phosphorylated Donor is not a nucleotide Near equilibrium rxn. Reversibility is important for reverse step in glucose synthesis (gluconeogenesis). Really steps 6&7 couple oxidation to phosphorylation of ADP
13
Glycolysis: Step 8, Phosphoglycerate Mutase -cofactor independant
iPGM -cofactor independant dPGM -cofactor dependant
14
Step 9, Enolase phosphomonoester Enol-phosphate ester
PEP: Very high P-group transferpotential
15
Glycolysis: Step 10, Pyruvate Kinase
2nd sub level phosphorylation 3rd metabolically irreverible rxn Reg allosteric and covalent modification
16
Glyceraldehyde-3-phosphate dehydrogenase
Glucose #1 ATP Phosphorylation Hexokinase ADP Glucose-6-phosphate Three Metabolically Irreversible Reactions Isomerization Glucose-6-phosphate isomerase Fructose-6-phosphate #3 ATP Phosphofructokinase-1 Phosphorylation ADP Fructose-1,6-bisphosphate Cleavage Aldolase Dihydroxyacetone phosphate Isomerization Trios phosphate isomerase Glyceraldehyde-3-phosphate Glyceraldehyde-3-phosphate NAD+ + Pi NAD+ + Pi Glyceraldehyde-3-phosphate dehydrogenase Oxidation and Phosphorylation NADH + H+ NADH + H+ 1,3-bisphosphoglycerate 1,3-bisphosphoglycerate ADP Substrate Level Phosphorylation Phosphoglycerate kinase ADP ATP ATP Most are near equilibrium 3-phosphoglycerate 3-phosphoglycerate Phosphoglycerate mutase Rearrangement 2-phosphoglycerate 2-phosphoglycerate Enolase H2O H2O Dehydration phosphoenolpyruvate phosphoenolpyruvate ADP ADP #10 ATP Pyruvate kinase Substrate Level Phosphorylation ATP pyruvate pyruvate
17
Energetics of Glycolysis
Hexokinase Phosphofructokinase 1 10. Pyruvate Kinase Enter the Le Chatelier Few large -G steps, irreversible, regulated * * * Most are near equilibrium and have G close to zero Steps 2, 4, 5, 6, 7, 8, 9
18
Physiological Regulation of Glycolysis
Hormones Involved High blood [Glc], insulin released Low blood [Glc], glucagon released Insulin Independent Uptake Brain Liver Red Blood Cells Insulin Dependent Uptake Muscle Adipose
19
Regulation of Glycolysis by Cellular Import
Hexose Transporters transport glucose into cells in an insulin dependent manner [Glucose] high in bloodsteam and low inside most cells- passive transport Exceptions Small intestine Kidney Which cell types are affected? High Insulin hormone and [Glc] stimulate increased rate of glucose intake Insulin binds receptor, GLUT4 hexose transporter able to bind cell surface
20
Enzymatic Regulation of Glycolysis
Not moving forward, stop converting ATP Cellular rxns are converting ATP and ADP, make more ATP You’ve committed! Bi-phosphated furanoses, keep pathway moving CAC intermediates, slow down, there is already adequate supply of energy Regulation network samples the condition of the cytoplasm and applies Principles of Supply and Demand
21
Glycolysis: Hexokinase Isozymes
Hexokinases (I-III) -regulated negatively by Glc-6-P -if later steps slow down, Glc-6P builds up I-III IV Isozymes Different inhibition profiles Location, Km Control point Glucokinase (IV) in Liver -regulated negatively by Fru-6-P -pulls glucose out of bloodstream until equil -liver can produce more Glc-6-P -converts Glucose to Glycogen storage Can’t leave the cell with negative charge
22
Regulation of Phosphofructokinase-1
Large oligomeric enzyme bacteria/mammals - tetramer yeast - octamer ATP - product of pathway - allosteric inhibitor AMP - allosteric activator - relieves inhibition by ATP Citrate - feedback inhibitor - regulates supply of pyruvate - links Glycolysis and CAC Fru-2,6-bisphosphate - strong activator - produced by PFK-2 when excess fru-6-phosphate - indirect means of substrate stimulation or feed forward activation
23
Regulation of Pyruvate Kinase
+ F 1,6 BP Inactivation by covalent modification -blood [Glc] drops, glucagon released -liver protein kinase A (PKA) turned on -PKA phosphorylates pyruvate kinase Allosteric (feed-forward) activation Fructose-1,6-bisphosphate -allosterically activates -produced in step three -links control steps together Allosteric inhibition by ATP -product of pathway and CAC High blood [Glc] Low blood [Glc]
Similar presentations
