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GLYCOLYSIS
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GLUCOSE TRANSPORTERS Transporter Location Characteristics
Na+/glucose transporters Gut Glucose-sodium symport Na+ independent facilitated diffusion-transporters GLUT1 All cells, RBCs, brain Low Km GLUT2 Liver, b cells of pancreas, kidney, intestine High Km GLUT3 Brain, most cell types GLUT4 Muscle, adipose tissue Insulin-dependent translocation to plasma membrane GLUT5 Intestine, liver Fructose absorption
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METABOLIC FATES OF GLUCOSE
Catabolized to produce ATP Stored as glycogen in liver and muscles Converted to fatty acids and stored as triglycerides in adipose tissue
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CARBOHYDRATE CATABOLISM
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GLYCOLYSIS A two-phase pathway in which
Glucose is oxidized into pyruvate NAD+ is reduced to NADH + H+ ATP is synthesized by substrate-level phosphorylation Pyruvate Moves on to the Krebs cycle in an aerobic environment Is reduced to lactate in an anaerobic environment
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GLYCOLYSIS – The phases
Glucose Fructose 1,6-bisphosphate 2 ATP I. Energy investment phase 2 Pyruvate 4 ATP 2 NADH II. Energy generation phase
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GLYCOLYSIS Step I. ATP ADP GLUCOSE 6- PHOSPHATE GLUCOSE Hexokinase
Glucokinase GLUCOSE
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Hexokinase/Glucokinase
Found in most tissues Broad specificity Low Km Low Vmax Makes glucose available to tissues at low blood glucose levels
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Hexokinase/Glucokinase
Found in liver and b cells of pancreas Broad specificity High Km High Vmax Clears glucose from blood after meals and at blood glucose levels > 100 mg/dl
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Phosphoglucose isomerase
GLYCOLYSIS Step II. FRUCTOSE 6- PHOSPHATE Phosphoglucose isomerase GLUCOSE 6- PHOSPHATE
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GLYCOLYSIS Step III. ATP ADP FRUCTOSE 1, 6- BISPHOSPHATE
Phosphofructo-kinase I ATP ADP FRUCTOSE 6- PHOSPHATE
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GLYCOLYSIS Steps IV, V. Aldolase DIHYDROXACETONE PHOSPHATE
GLYCERALDEHYDE 3-PHOSPHATE DIHYDROXACETONE PHOSPHATE Triose phosphate isomerase FRUCTOSE 1, 6- BISPHOSPHATE
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GLYCOLYSIS Step VI. Pi NAD+ NADH + H+ 1,3- BISPHOSPO-GLYCERATE
Glyceraldehyde 3-phosphate dehydrogenase GLYCERALDEHYDE 3-PHOSPHATE
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Phosphoglycerate kinase
GLYCOLYSIS Step VII. 3- PHOSPHO-GLYCERATE Phosphoglycerate kinase ADP ATP 1,3- BISPHOSPHO-GLYCERATE
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SUBSTRATE-LEVEL PHOSPHORYLATION
High-energy phosphate groups are transferred directly from phosphorylated substrates to ADP
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2, 3- BISPHOSPHOGLYCERATE
Phosphoglycerate kinase ADP ATP Phosphatase H2O P-OH 2, 3- BISPHOSPHO-GLYCERATE Mutase
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ARSENATE POISONING GLYCOLYSIS CONTINUES… ENERGY IS DEPLETED
GLYCERALDEHYDE 3-PHOSPHATE Pi Pi ARSENATE Glyceraldehyde 3-phosphate dehydrogenase NAD+ GLYCOLYSIS CONTINUES… ENERGY IS DEPLETED H+ + NADH 1,3- BISPHOSPOGLYCERATE ADP ATP 3- PHOSPHOGLYCERATE
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Phosphoglycerate mutase
GLYCOLYSIS Step VIII. 3- PHOSPHO-GLYCERATE 2- PHOSPHO-GLYCERATE Phosphoglycerate mutase
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GLYCOLYSIS Step IX. H2O Enolase PHOSPHOENOLPYRUVATE
2- PHOSPHO-GLYCERATE FLOURIDE
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GLYCOLYSIS Step X. PHOSPHOENOLPYRUVATE PYRUVATE ATP ADP
Pyruvate kinase ADP ATP PYRUVATE PHOSPHOENOLPYRUVATE
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2 PYRUVATE + 2NADH + 2H+ + 2ATP + 2H2O
GLYCOLYSIS: SUMMARY GLUCOSE + 2NAD+ +2Pi + 2ADP 2 PYRUVATE + 2NADH + 2H+ + 2ATP + 2H2O
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THE FATES OF PYRUVATE ANAEROBIC CONDITIONS AEROBIC CONDITIONS
Reduced to lactate (In RBCs, the kidney medulla, lens and cornea of the eye, testes, leukocytes and in muscles during intensive exercise) AEROBIC CONDITIONS oxidative decarboxylation to Acetyl CoA (in tissue with high oxidative capacity e.g. cardiac muscle, brain etc. )
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ANAEROBIC CONDITIONS PYRUVATE LACTATE lactate dehydrogenase NADH + H+
GLYCERALDEHYDE 3-PHOSPHATE 1,3- BISPHOSPHO-GLYCERATE LACTATE NADH + H+ NAD+ lactate dehydrogenase PYRUVATE
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ANAEROBIC GLYCOLYSIS GLUCOSE + 2Pi + 2ADP
2 Lactate + 2ATP + 2H2O + 2H+
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Pyruvate dehydrogenase complex
AEROBIC GLYCOLYSIS ACETYL CoA Pyruvate dehydrogenase complex (E1 + E2 + E3) CoA-SH NADH + H+ NAD PYRUVATE
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For each molecule of glucose entering glycolysis, two molecules of acetyl CoA enter the Krebs cycle
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REGULATION OF GLYCOLYSIS
Hexokinase/Glucokinase Phosphofructokinase Pyruvate Kinase
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REGULATION OF HEXOKINASE
GLUCOSE ATP Hexokinase _ ADP GLUCOSE 6- PHOSPHATE
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REGULATION OF GLUCOKINASE
GLUCOSE + ATP Glucokinase _ ADP GLUCOSE 6- PHOSPHATE FRUCTOSE 6- PHOSPHATE
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REGULATION OF GLUCOKINASE
GLUCOSE ATP ADP GLUCOSE 6- PHOSPHATE Glucokinase Glucokinase Nucleus GKRP GK FRUCTOSE 6- PHOSPHATE
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REGULATION OF PHOSPHOFRUCTOKINASE 1
FRUCTOSE 6- PHOSPHATE _ ATP, CITRATE + AMP, Fructose 2,6 bisphosphate Phosphofructokinase 1 FRUCTOSE 1,6- BISPHOSPHATE
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REGULATION OF PHOSPHOFRUCTOKINASE 1
FRUCTOSE 6- PHOSPHATE Phosphofructokinase 2 Starvation Glucagon cAMP Protein kinase Well fed state Insulin cAMP protein kinase P Kinase Phosphatase FRUCTOSE 2,6- BISPHOSPHATE
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REGULATION OF PYRUVATE KINASE
FRUCTOSE 1,6- BISPHOSPHATE + Pyruvate kinase PYRUVATE
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REGULATION OF PYRUVATE KINASE
PHOSPHOENOLPYRUVATE Starvation Glucose Glucagon cAMP Protein kinase A P Pyruvate kinase GLUCONEOGENESIS PYRUVATE
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GLYCOLYSIS AND OTHER METABOLIC PATHWAYS
GLUCOSE GLUCOSE 6 PHOSPHATE 1, 3 BISPHOSPHOGLYCERATE 3 PHOSPHOGLYCERATE PYRUVATE ACETYL CoA 5-C sugars TCA cycle Glu & other amino acids Serine 2, 3 BPG Alanine Glycerol-P Fatty acids TGs
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THANK YOU!
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