3 CarbohydratesCarbohydrates are called carbohydrates because they are essentially hydrates of carbon (i.e. they are composed of carbon and water and have a composition of (CH2O)n.The major nutritional role of carbohydrates is to provide energy and digestible carbohydrates provide 4 kilocalories per gram. No single carbohydrate is essential, but carbohydrates do participate in many required functions in the body.
9 Glycolysis What is glycolysis? Ten step metabolic pathway to convert glucose into two moleculesof pyruvate and two moleculeseach of NADH and ATP. All carbohydrates to be catabolizedmust enter the glycolytic pathway.- Glycolysis is central in generatingboth energy and metabolicintermediaries.
10 The Glycolysis Pathway Major anaerobic pathway in all cellsNAD+ is the major oxidantRequires PO4Generates 2 ATP’s per glucose oxidizedEnd product is lactate (mammals) or ethanol (yeast)Connects with Krebs cycle via pyruvate
11 Phase I. Energy Investment. Enzymes = hexokinase or glucokinase 1- Glucose is phosphorylated. Glucose enters a cell through a specific glucose transport process. It is quickly phosphorylated at the expense of an ATP. The investment of an ATP here is called “priming.”Enzymes = hexokinase orglucokinase2. Isomerization of glucose 6-phosphateEnzyme = phosphoglucoisomerase
13 Enzyme = phosphofructokinase 3- Second phosphorylationEnzyme = phosphofructokinaseATP ADPfructose 1,6 bisphosphatesecond ATP investmenthighly exergonic, essentiallyirreversible, G°´= kJ/mole- highly regulated, modulating carbonflux through glycolysis in responseto energy and carbon requirements
14 4- Cleavage to two triose phosphates Enzyme = aldolase HC=O H2COPHCOH O=CHCOP CH2OHHglyceraldehyde dihydroxyacetone3-phosphate phosphatewhere P = phosphate cleaves a 6C sugar to 2 3C sugars G°´= kJ/mole, driven by next Rx.
17 only glyceraldehyde 3-phosphate can be used further in glycolysis. allows interconversion of two triose phosphate productsof aldolase cleavageonly glyceraldehyde 3-phosphate can be used furtherin glycolysis. aldose-ketose isomerization similarto phosphoglucoisomerase rxnallows dihydroxyacetone phosphate to be metabolizedas glyceraldehyde 3-phosphatereversible,G°´= +7.5 kJ/mole.This is important in gluconeogenesis
18 Second Phase: End of First Phase: Production of two glyceraldehyde ****************************************End of First Phase: Production of two glyceraldehyde3-phosphate molecules from oneglucose molecule with theexpenditure of two ATPs. Therefore: the energy yields of thefollowing steps are multipled by two.*****************************************Second Phase:
19 + 6- Oxidation of glyceraldehyde 3-phosphate Enzyme= glyceraldehyde-3-phosphatedehydrogenaseOHOPOOH NAD NADH OOPOH C=OO HCOHH2CO- P+glyceraldehyde 3-phosphate ,3 bisphosphoglycerate-addition of phosphate, oxidation,production of NADH, formation ofhigh energy compound
20 - first substrate level phosphorylation, yielding ATP 7- Transfer of phosphate to make ATPEnzyme = phosphoglycerate kinaseO=C-O- P O=C-OH PHC-OH + P HC-OH PH2C-O-P P H2C-O-P PAdenosine Adenosine1,3PG ADP phosphoglycerate ATP- first substrate level phosphorylation,yielding ATP- 2 1,3 bis PG yield 2 ATPs, thus so farATP yield = ATP input- high free energy yield, G°´= -18.8kJ/mole drives several of the previous steps.
21 8- Phosphate shift setup Enzyme= phosphoglycerate mutase - shifts phosphate from position 3 to 2- reversible, ΔG = kJ/mole
22 9- Generation of second very high energy compound Enzyme = enolase -- little energy change in this reaction,ΔG = +1.7 kJ/mole because theenergy is locked into enolphosphate
23 phosphoenolpyruvate pyruvate second substrate level phosphorylation 10- Final generation of ATPEnzyme = pyruvate kinasePO H ADP ATP O-OOC-C=CH OOC-C-CH3phosphoenolpyruvate pyruvatesecond substrate level phosphorylationyielding ATP- highly exergonic reaction,irreversible, ΔG = kJ/mole.
28 Regulation of Glycolysis 6-phosphofructokinase-1Allosteric enzymenegative allosteric effectorsCitrate , ATPPositive allosteric effectorsAMP, fructose1,6-bisphosphate, fructose2,6- bisphosphateChanges in energy state of the cell (ATP and AMP)
30 Regulation of Glycolysis Pyruvate KinaseAllosteric enzymeInhibited by ATP.Isoenzyme in liveractivated by fructose 1,6 bisphosphateinhibited by alanineRegulated by phosphorylation and dephosphorylationHexokinaseDifferent isoenzymesHexokinase IVglucose 6-phosphate is an allosteric inhibitorpromote biosynthesis