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GLYCOLYSISGLYCOLYSIS
TransporterTransporter LocationLocation CharacteristicsCharacteristics
Na+/glucose transporters
Gut Glucose-sodium symport
Na+ independent facilitated diffusion-transporters
GLUT1 All cells, RBCs, brain Low Km
GLUT2 Liver, cells of pancreas, kidney, intestine
High Km
GLUT3 Brain, most cell types Low Km
GLUT4 Muscle, adipose tissue
Insulin-dependent translocation to plasma membrane
GLUT5 Intestine, liver Fructose absorption
GLUCOSE GLUCOSE TRANSPORTERSTRANSPORTERS
METABOLIC FATES OF METABOLIC FATES OF GLUCOSEGLUCOSE
• Catabolized to produce ATP • Stored as glycogen in liver and
muscles• Converted to fatty acids and stored
as triglycerides in adipose tissue
CARBOHYDRATE CARBOHYDRATE CATABOLISMCATABOLISM
GLYCOLYSISGLYCOLYSIS• 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
GLYCOLYSIS – The GLYCOLYSIS – The phasesphases
Glucose
Fructose 1,6-bisphosphate
2 ATPI. Energy investment phase
2 Pyruvate
4 ATP
2 NADH
II. Energy generation phase
GLYCOLYSISGLYCOLYSISStep I.Step I.
GLUCOSE GLUCOSE 6- PHOSPHATE
ATP ADP
HexokinaseGlucokinase
Hexokinase/GlucokinaseHexokinase/Glucokinase
Hexokinase– Found in most tissues– Broad specificity
– Low Km
– Low Vmax
Makes glucose available to tissues at low blood glucose levels
Hexokinase/GlucokinaseHexokinase/GlucokinaseGlucokinase
–Found in liver and cells of pancreas–Broad specificity
–High Km
–High Vmax
Clears glucose from blood after meals and at blood glucose
levels > 100 mg/dl
GLYCOLYSISGLYCOLYSISStep II.Step II.
GLUCOSE 6- PHOSPHATE
FRUCTOSE 6- PHOSPHATEPhosphoglucose
isomerase
GLYCOLYSISGLYCOLYSISStep III.Step III.
FRUCTOSE 6- PHOSPHATE
FRUCTOSE 1, 6- BISPHOSPHATEPhosphofructo
-kinase I
ATP
ADP
GLYCOLYSISGLYCOLYSISSteps IV, V.Steps IV, V.
FRUCTOSE 1, 6- BISPHOSPHATE
Triose phosphat
e isomerase
Aldolase
GLYCERALDEHYDE 3-PHOSPHATE
DIHYDROXACETONE PHOSPHATE
GLYCOLYSISGLYCOLYSISStep VI.Step VI.
GLYCERALDEHYDE 3-PHOSPHATE
1,3- BISPHOSPO-GLYCERATE
PiNAD+ NADH + H+
Glyceraldehyde 3-phosphate
dehydrogenase
GLYCOLYSISGLYCOLYSISStep VII.Step VII.
1,3- BISPHOSPHO-GLYCERATE 3- PHOSPHO-GLYCERATEPhosphoglycerate
kinase
ADP ATP
SUBSTRATE-LEVEL PHOSPHORYLATION
High-energy phosphate groups are transferred directly from phosphorylated substrates to ADP
1,3- BISPHOSPHO-GLYCERATE
3- PHOSPHO-GLYCERATEPhosphoglycerate
kinase
ADP ATP
2, 3- BISPHOSPHO-GLYCERATE
Mutase Phosphatase
H2O
P-OH
2, 3- BISPHOSPHOGLYCERATE2, 3- BISPHOSPHOGLYCERATE
Pi
ARSENATE POISONINGARSENATE POISONING
GLYCERALDEHYDE 3-PHOSPHATE
1,3- BISPHOSPOGLYCERATE
3- PHOSPHOGLYCERATE
Glyceraldehyde 3-phosphate
dehydrogenase
PiNAD+
H+ + NADH
ADP
ATP
ARSENATE
GLYCOLYSIS CONTINUES…
ENERGY IS DEPLETED
GLYCOLYSISGLYCOLYSISStep VIII.Step VIII.
3- PHOSPHO-GLYCERATE
2- PHOSPHO-GLYCERATE
Phosphoglycerate mutase
FLOURIDE
GLYCOLYSISGLYCOLYSISStep IX.Step IX.
PHOSPHOENOLPYRUVATEEnolase
H2O
2- PHOSPHO-GLYCERATE
GLYCOLYSISGLYCOLYSISStep X.Step X.
PHOSPHOENOLPYRUVATE
Pyruvate kinase
ADPATP
PYRUVATE
GLYCOLYSIS: SUMMARYGLYCOLYSIS: SUMMARY
GLUCOSE + 2NAD+ +2Pi + 2ADP
2 PYRUVATE + 2NADH + 2H+ + 2ATP + 2H2O
THE FATES OF PYRUVATETHE FATES OF PYRUVATE
• ANAEROBIC CONDITIONSReduced to lactate(In RBCs, the kidney medulla, lens and cornea
of the eye, testes, leukocytes and in muscles during intensive exercise)
• AEROBIC CONDITIONSoxidative decarboxylation to Acetyl CoA (in tissue with high oxidative capacity e.g. cardiac muscle, brain etc. )
ANAEROBIC CONDITIONSANAEROBIC CONDITIONS
PYRUVATE LACTATE
NADH + H+ NAD+
lactate dehydrogenase
GLYCERALDEHYDE 3-PHOSPHATE
1,3- BISPHOSPHO-GLYCERATE
ANAEROBIC GLYCOLYSISANAEROBIC GLYCOLYSIS
GLUCOSE + 2Pi + 2ADP
2 Lactate + 2ATP + 2H2O + 2H+
AEROBIC GLYCOLYSISAEROBIC GLYCOLYSIS
PYRUVATE ACETYL CoAPyruvate
dehydrogenase complex
(E1 + E2 + E3)
CoA-SH NADH + H+
NAD
For each molecule of glucose entering glycolysis, two molecules of acetyl CoA enter the Krebs cycle
REGULATION OF REGULATION OF GLYCOLYSISGLYCOLYSIS
•Hexokinase/GlucokinaseHexokinase/Glucokinase•PhosphofructokinasePhosphofructokinase•Pyruvate KinasePyruvate Kinase
REGULATION OF REGULATION OF HEXOKINASEHEXOKINASE
GLUCOSE
GLUCOSE 6- PHOSPHATE
ATP
ADP
Hexokinase
_
GLUCOSE
GLUCOSE 6- PHOSPHATE
ATP
ADP
Glucokinase
FRUCTOSE 6- PHOSPHATE
+
_
REGULATION OF REGULATION OF GLUCOKINASEGLUCOKINASE
Nucleus
GKRP
GLUCOSE
Glucokinase
FRUCTOSE 6- PHOSPHATE
ATP
ADP
GLUCOSE 6- PHOSPHATE GK
Glucokinase
REGULATION OF REGULATION OF GLUCOKINASEGLUCOKINASE
REGULATION OF PHOSPHOFRUCTOKINASE
1FRUCTOSE 6- PHOSPHATE
FRUCTOSE 1,6- BISPHOSPHATE
Phosphofructokinase 1+ AMP, Fructose AMP, Fructose 2,6 2,6 bisphosphatebisphosphate
_ ATP, ATP, CITRATECITRATE
REGULATION OF PHOSPHOFRUCTOKINASE
1FRUCTOSE 6- PHOSPHATE
FRUCTOSE 2,6- BISPHOSPHATE
Phosphatase
Well fed state InsulincAMPprotein kinase
Starvation Glucagon cAMP Protein kinase
Phosphofructokinase 2
KinaseP
REGULATION OF REGULATION OF PYRUVATE KINASEPYRUVATE KINASE
FRUCTOSE 1,6- BISPHOSPHATE
PYRUVATE
Pyruvate kinase
+
REGULATION OF PYRUVATE KINASEPYRUVATE KINASE
PHOSPHOENOLPYRUVATE
PYRUVATE
Starvation Glucose Glucagon cAMP Protein kinase A
Pyruvate kinase
P
GLUCONEOGENESIS
GLYCOLYSIS AND OTHER METABOLIC GLYCOLYSIS AND OTHER METABOLIC PATHWAYSPATHWAYSGLUCOSE
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
THANK YOU!