Outline

Introduction (Figure 13.1)

> Anaerobic Metabolism

Glycolysis Overview (Figure 13.3)

> Relation to Other Pathways

> > Entry Point for Hexose Sugars (Figure 13.12)
> > Energy Investment/Generation (Figure 13.2)

> Anaerobic/Aerobic Glycolysis

> > Early Atmosphere
> > Reoxidize NADH to Maintain Steady State
> > Fermentation (no net change in oxidation state) = Anaerobic Glycolysis

> > > Pyruvate/Lactate
> > > Alcohol DH

> > Respiration (oxidative breakdown and energy release by reaction with oxygen)
> > Respiration Using Oxygen = Aerobic Glycolysis

> Crucial Early Experiments

> > Buchners - 1897 - Cell Free fermentation
> > Harden/Young - 1905 Phosphate Stimulates fermentation of glucose
> > Embden/Meyerhof/Warburg - 1930s - Reactions of glycolysis

> Strategy of Glycolysis

> > Glycolysis occurs in cytosol
> > Overview (Figure 13.3)
> > 1,3BPG and PEP energy of hydrolysis (Figure 3.7)
> > Types of phosphorylation

> > > Substrate-level (Glycolysis)
> > > Oxidative phosphorylation (Driven by electron transport)
> > > Photophosphorylation (Photosynthesis)

Reactions of Glycolysis

> Energy Investment (Figure)

> > Reaction 1 - Structures / Enzyme / Summary
> > Reaction 2 - Structures / Enzyme / Summary
> > Reaction 3 - Structures / Enzyme / Summary
> > Reaction 4 - Structures / Enzyme / Summary (Figure 13.4)
> > Reaction 5 - Structures / Enzyme / Summary

> Energy Generation (Figure on page 454)

> > Reaction 6 - Structures / Enzyme / Summary (Figure 13.5)
> > Reaction 7 - Structures / Enzyme / Summary
> > Reaction 8 - Structures / Enzyme / Summary
> > Reaction 9 - Structures / Enzyme / Summary
> > Reaction 10 - Structures / Enzyme / Summary

> Overall Summary (Table 13.1)

Metabolic Fates of Pyruvate (Pyruvate/Lactate/Ethanol Metabolism)

> Lactate Metabolism

> > Lactate Dehydrogenase Reaction
> > Isoenzymes of Lactate Dehydrogenase

> Ethanol Metabolism

> > Pyruvate decarboxylase / Alcohol dehydrogenase (Figure)

> > > Thiamine pyrophosphate requirement

Energy And Electron Balance Sheets (Figure 13.6)

ATP Energy Summaries of Glycolysis

> Glucose -> 2 Lactate (lactic acid fermentation)
> Glucose -> 2 Ethanol (alcoholic fermentation)
> Glucose -> 2 Pyruvate (aerobic subtotal)
> 2 NADH -> 6 ATP (aerobic conversion)
> Glucose -> 2 Pyruvate overall (oxidative)

> Metabolism to lactate or ethanol non-oxidative

> More ATPs from Citric Acid Cycle (38 total)

Regulation of Glycolysis

> The Pasteur Effect

> > Inhibition of glycolysis by oxygen
> > Intermediates after F6P decrease with O 2

> Oscillations of Glycolytic Intermediates

> > Activity of glycolysis depends on adenylate energy charge (Figure 13.8)

> Allosteric Regulation of Phosphofructokinase

> > PFK Activator = Fructose-2,6-bisphosphate (Figure 13.9)

> > > PFK-2

> > > > Phosphorylation/dephosphorylation - Figure 16.7

> > Other PFK Activators = AMP, ADP
> > PFK Inhibitors = ATP and Citrate
> > PFK is the enzyme through which adenylate energy charge is controlled

> Control of Pyruvate Kinase

> > Inhibitors = ATP and Acetyl CoA
> > Feedforward Activation by F1,6BP

> Glycolysis as Both a Catabolic and an Anabolic Pathway

> (Relationship of Glycolysis to Other Metabolic Pathways)

> > Biosynthetic intermediates from glycolysis (Figure 13.10)
> > Regulatory relationships with other pathways (Figure 13.11)

Entry of Other Sugars into the Glycolytic Pathway

Catabolism of Other Saccharides

> Monosaccharide Metabolism (Figure 13.12)
> Galactose Utilization (Summary)

> > Derived from Lactose
> > Conversion to glucose-6-phosphate (Figure 13.13)

> > > Galactose-1-phosphate formation by galactokinase
> > > UDP-galactose formation (UDP-Glc:GalP uridylyl transferase)
> > > UDP-glucose formation (UDP-galactose 4-epimerase) (Figure 13.14)
> > > Galactose-1-phosphate release (UDP-Glc:GalP uridylyl transferase)
> > > Conversion to glucose-6-phosphate (phosphoglucomutase)

> > Lactose synthesis in milk

> > > Lactose synthase

> > Galactosemia

> Fructose Utilization

> > Fructose-6-phosphate (from hexokinase)

> > Fructose-1-phosphate (from fructokinase then cleavage by aldolase B)

> Mannose Utilization

> > Mannose-6-phosphate formation (catalyzed by hexokinase)

> > Conversion of mannose-6-phosphate to fructose-6-phosphate

> Disaccharide Metabolism (See Figure)

> > Maltose ->2 Glucose (catalyzed by maltase)

> > Lactose -> Galactose + Glucose (catalyzed by lactase)

> > Sucrose -> Fructose + Glucose (catalyzed by sucrase)

> > Lactose intolerance

> > Bacterial sucrose enzyme (sucrose phosphorylase)

> Glycerol Metabolism

> > From fat digestion

> > Glycerol kinase (glycerol -> glycerol-3-phosphate)

> > Glycerol-3-phosphate dehydrogenase (glycerol-3-phosphate -> DHAP)

Catabolism of Polysaccharides

> Hydrolytic and Phosphorolytic Cleavages (Figure 13.15)

> > Phosphorylase vs. phosphatase
> > Energy considerations

> Starch and Glycogen Digestion

> > -Amylase (Figure 13.16)

> > > In saliva
> > > Cleaves internal (1,4) linkages of starch and glycogen
> > > Limit Dextrin

> Glycogen Mobilization (Glycogen Breakdown)

> > Glycogen phosphorylase
> > Starch phosphorylase
> > Debranching activity (Figure 13.17)
> > Conversion of glucose-1-phosphate to glucose-6-phosphate

> > > Phosphoglucomutase

> Regulation of Glycogen Breakdown (Figure 13.18)

> > Structure of glycogen phosphorylase

> > > Phosphorylation by phosphorylase b kinase (Calmodulin effects)
> > > Dephosphorylation by phosphorylase phosphatase

> > Control of Phosphorylase Activity

> > > Phosphorylase b kinase activation by cAMP-dependent protein kinase
> > > Reciprocal effect on glycogen synthesis
> > > Role of epinephrine
> > > Kinase cascade

> > Proteins in the Glycogenolytic Cascade

> > > Adenylate cyclase
> > > cAMP-dependent protein kinase
> > > Phosphorylase b kinase
> > > Calmodulin (Figure 13.20)
> > > Glycogen phosphorylase

> > Nonhormonal Control of Glycogenolysis

> > Activation of glycogen phosphorylase b by AMP