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

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