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 O2

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