1 Metabolism of Carbohydrates The Energy Metabolism of Glucose Entry of other Carbohydrates into Glycolysis Pyruvate Metabolism Biosynthesis of Carbohydrates

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Metabolism of CarbohydratesMetabolism of Carbohydrates

The Energy Metabolism of Glucose

Entry of other Carbohydrates into Glycolysis

Pyruvate Metabolism

Biosynthesis of Carbohydrates

Regulation of Carbohydrate Metabolism

The Energy Metabolism of Glucose

Entry of other Carbohydrates into Glycolysis

Pyruvate Metabolism

Biosynthesis of Carbohydrates

Regulation of Carbohydrate Metabolism

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Metabolism of carbohydratesMetabolism of carbohydrates

All organisms obtain energy from the oxidation of glucose and other carbohydrates.

In some cells and organisms, glucose is the major or sole source of energy:

brainbrain

erythrocyteserythrocytes

many bacteriamany bacteria

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Carbohydrate metabolismCarbohydrate metabolism

GlycolysisGlycolysisThe main pathway for glucose oxidation. It forms pyruvate anaerobically.

Phosphogluconate pathwayPhosphogluconate pathwayAn auxiliary route for glucose oxidation in animals. It produces ribose-5-phosphate.

GluconeogenesisGluconeogenesisPathway for the synthesis of glucose from pyruvate.

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Energy metabolism of glucoseEnergy metabolism of glucose

Glycogen (animals)Starch (plants)

Glucose Pyruvate Acetyl CoA

Lactate

Ethanol

Ribose-5-phosphate+ NADPH + H+

Disaccharides

ATP +NADH + H+

catabolism

anabolism

phosphogluconatepathway

glycolysis

gluconeo-genesis

aerobic

anaerobic,muscles

anaerobic,yeast

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GlycolysisGlycolysis

First stage of carbohydrate catabolism.

Simple sugars are broken down to pyruvate.

Anaerobic process - no oxygen needed.

All life uses this process.

RequiresRequires

glucose, 2 ADP, 2 ATP, 2 NADglucose, 2 ADP, 2 ATP, 2 NAD++, 2 PO, 2 PO44==

10 different enzymes10 different enzymes

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First five reactions of glycolysisFirst five reactions of glycolysis

glucose

glucose-6-P

fructose-6-P

fructose-1,6-bisP

glyceraldehyde-3-P dihydroxyacetone-P

ATP

ADP

ATP

ADP

6 carbonstage

Requiresenergy

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Reactions of glycolysisReactions of glycolysis

1,3-bisphosphoglycerate

3-phosphoglycerate

2-bisphosphoglycerate

phosphoenolpyruvate

pyruvate

glyceraldehyde-3-P

ATPADP

ATPADP

NAD+

NADH + H+

H2O

Pi

3 carbonstage

Double thissince two pyruvateare made.

3 carbonstage

Double thissince two pyruvateare made.

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Overall glycolysisOverall glycolysis

glucose 2 ADP + 2 PO4= + 2 NAD+

2 pyruvate + 2 NADH + 2 H2O + 2 ATP

Net energy produced is 2 ATPNet energy produced is 2 ATP

In addition, the two pyruvate can go on to the citric acid cycle to produce more energy.

10 enzymes

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Entry of other carbohydratesinto glycolysis


Dietary carbohydratesDietary carbohydrates

PolysaccharidesPolysaccharidesStarches and glycogen are

hydrolyzed to glucose by amylase in the mouth.

DisaccharidesDisaccharidesMaltose, sucrose and lactose.

Each is hydrolyzed to a different pair of monosaccharides.

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DisaccharidesDisaccharides

maltose + H2O 2 glucose

sucrose + H2O fructose + glucose

lactose + H2O glucose + galactose

maltase

invertase(bacteria)

sucrase(animals)

lactase

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FructoseFructoseEnters glycolysis by two different pathways depending on the tissue.

Skeletal musclesSkeletal musclesThe glycolytic enzyme, hexokinase accepts fructose as a substrate but with only 5% of the affinity of glucose.

It only requires one phosphoryl transfer step to enter glycolysis.

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FructoseFructose

Liver CellsLiver CellsThey have another enzyme, fructokinase.

• It has a stronger affinity for fructose.

• It catalyzes phosphoryl group transfer from ATP to produce fructose-1-phosphate.

An aldolase-type cleavage and additional phosphorylation must also occur.

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GalactoseGalactoseFive reactions are required to transform it into glucose-6-phosphate.

Galactose

Galactose-1-phosphate

UDP-galactose UDP-glucose

Glucose-1-phosphate

Glucose-6-phosphate

galactokinase

galactose-1-phosphate uridyl

transferaseUDP-galactose-4-epimerase

UDP-glucosepyrophosphorylase

Phospho-glucomutase

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Pyruvate metabolismPyruvate metabolism

Glycolysis ends with the production of two pyruvate per molecule of glucose.

Several things can happen to the pyruvate based on the organism and cellular conditions.

FermentationFermentation - subsequent processing under anaerobic conditions.

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FermentationFermentation

An anaerobic process beyond glycolysis.

In our body it is used to make NAD+ when there is not enough oxygen.

NAD+ must be regenerated from NADH or glycolysis will stop.

We’ll look at two types of fermentation:

Lactate and Ethanol.Lactate and Ethanol.

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Lactate fermentationLactate fermentation

LactateLactateProduced by muscles when the body can’t supply enough oxygen.

pyruvatepyruvate lactatelactate

Anaerobic conversion of pyruvate to lactate permits regeneration of NAD+.

Body can then make more ATP - at a cost.Creates an oxygen debt.

Body must take in extra O2 to oxidize lactate.

NADH + HNADH + H++NADNAD++

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Alcohol fermentationAlcohol fermentation

Used by anaerobic bacteria to obtain additional energy from glucose.

pyruvatepyruvate

acetaldehyde + COacetaldehyde + CO22

ethanolethanol

pyruvatepyruvatedecarboxylasedecarboxylase

alcoholalcoholdehydrogenasedehydrogenase

NADH + HNADH + H++

NADNAD++

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Biosynthesis of carbohydratesBiosynthesis of carbohydrates

GluconeogenesisGluconeogenesisSynthesis of glucose from

noncarbohydrate precursors.

• The liver is the major site for glucose synthesis in higher animals. Pyruvate, lactate, glycerol and some amino acids act as precursors.

• In microorganisms, it is synthesized from acetate and propionate.

• Plants produce it photosynthetically.

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Biosynthesis of carbohydratesBiosynthesis of carbohydrates

Skeletal musclesGlycogen

glucose-6-Pexercise

restglucose-6-P

pyruvate

lactate

Skeletal musclesGlycogen

glucose-6-Pexercise

restglucose-6-P

pyruvate

lactate

LiverGlycogen

glucose-6-P

glucose-6-P

pyruvate

lactate

LiverGlycogen

glucose-6-P

glucose-6-P

pyruvate

lactate

glucose

Muscles lack enzyme needed to convert pyruvate toglucose-6-P. Must be sent to liver.

Blood

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GluconeogenesisGluconeogenesis

Stage I

mit

och

on

dri

a

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Glycogen

Glucose

UDP-glucose

+ UDP

H O2Pi

ATP

H O2

Pi

Fructose-1,6-bisphosphate

Glyceraldehyde-3-phosphate

Phosphoenolpyruvate

3-Phosphoglycerate

2-Phosphoglycerate

Glucose-1-phosphate

Glucose-6-phosphate

Fructose-6-phosphate

ATP

Stage III

Stage II

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The process is sometimes called ‘reverse glycolysis’ but that is a misnomer.

Only seven of the ten steps in glycolysis are reversible. The three steps to be bypassed are:

1. glucose + ATP glucose-6-phosphate + ADP

3. fructose-6-phosphate + ATP fructose-1,6 -bisphosphate + ADP

10. PEP + ADP pyruvate + ATP

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Bypass I.Bypass I. Pyruvate Phosphoenolpyruvate

• This reaction has the highest energy barrier of any reaction in the pathway.

• In higher animals, it begins with pyruvate in the mitochondrial matrix.

• Pyruvate is carboxylated to oxaloacetate by pyruvate carboxylase.

• Only mitochondria have the proper enzyme and it requires biotin as a cofactor.

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Bypass I.Bypass I. Overall reaction

pyruvate + phosphoenolpyruvate +

ATP + GTP ADP + GDP + Pi

Gluconeogenesis from lactate is also an important anabolic process.

It requires initial conversion to pyruvate as shown earlier and requires the same amount of ATP and GTP.

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Bypass IIBypass IIFructose-1,6-bisphosphate Fructose-6-phosphate

PhosphofructokinasePhosphofructokinase

• Major regulatory enzyme in glycolysis.

• Catalyzes the irreversible phosphoryl transfer from ATP to fructose-6-phosphate.

In gluconeogenesis, the phosphoryl group is removed by hydrolysis, catalyzed by fructose-1,6-bisphosphatase.

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Fructose-6-phosphate

Fructose-1,6-bisphosphate

ATP

H2O

Pi

phospho-fructokinase

fructose-1,6-bisphosphatase

glu

con

eog

en

esi

sgly

coly

sis

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Bypass III.Bypass III.Glucose-6-phosphate Glucose + Pi

The final step is the removal of the phosphoryl group from glucose-6-phosphate. The enzyme, glucose-6-phosphatase catalyzes this hydrolysis.

glucose-6-phosphate + H2O glucose + Pi

glucose-6-phosphatase

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Synthesis of disaccharidesand polysaccharides

Synthesis of disaccharidesand polysaccharides

Activation of glucose and galactose.Activation of glucose and galactose.

• Not all glucose is immediately required for energy or other metabolic uses.

• Higher animals store excess as glycogen which is mobilized when needed for energy or other uses.

• In plants, glucose is the building block for sucrose, starch and cellulose.

• Nucleotide diphosphate sugars are used for synthesis.

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Activation of glucose and galactose

Activation of glucose and galactose

Nucleotide diphosphate sugars (NDP sugars)Nucleotide diphosphate sugars (NDP sugars)

Used primarily to mark sugars to be set aside for bisynthetic purposes.

Synthesis of NDP-glucose.Synthesis of NDP-glucose.

NTP + glucose-1-phosphate NDP-glucose + PP i

NTP = nucleotide triphosphate, ATP, UTP or GTPEnzyme = UDP-glucose pyrophosphorylase

ADP-glucose pyrophosphorylaseGDP-glucose pyrophosphorylase

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Synthesis of UDP-galactoseSynthesis of UDP-galactose

Two possible routesTwo possible routes

Isomerization of UDP-glucoseIsomerization of UDP-glucose

UDP-glucose UDP-galactose

Enzyme = UDP-glucose-4-epimerase

Exchange of UDPExchange of UDP

galactose-1-phosphate + UDP-glucose UDP-galactose + glucose-1-P

Enzyme = glactose-1-phosphate uridyl transferase

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Synthesis of glycogenSynthesis of glycogen

Glucose, activated and tagged by attachment of UDP is added to the nonreducing ends of an existing glycogen.

Glycogen synthase catalyzes the formation of a new (1 4) glycosidic linkage.

UDP-glucose + (glucose)n + H2O

(glucose)n+1 + UDP

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Synthesis of starchSynthesis of starch

Similar to glycogen formation except glucose is activated by ADP, not UDP.

Starch synthase catalyzes the addition of glucose to an existing starch molecule by formation of (1 4) glycosidic linkage.

ADP-glucose + (glucose)n

(glucose)n+1 + ADP

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Synthesis of lactoseSynthesis of lactose

This disaccharide is actively synthesized in the mammary glands of mammals.

It is produced by combining activated galactose with glucose using lactose synthase. A (1 4) linkage results.

UDP-galactose + glucose

UDP + lactose

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Synthesis of sucroseSynthesis of sucrose

Sucrose is present in most fruits and vegetables. It is produced by a two step process.

UDP-glucose + fructose-6-phosphate

sucrose-6-phosphate + UDP sucrose + Pi

sucrose-6-phosphatesynthase

phosphatase

H2O

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Synthesis of celluloseSynthesis of cellulose

Cellulose- major structural polysaccharide in cell walls of plants and some bacteria.

It’s synthetic route is similar to starch except a (1 4) linkage is produced.

UDP-glucose or GDP-glucose + (glucose)n

UDP or GDP + (glucose)n+1

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Regulation of glycolysisRegulation of glycolysis

As with all metabolic pathways, glycolysis is under constant control by the body.

The process is regulated by three enzymes:

hexokinasehexokinaseinhibited by glucose 6-phosphate

phosphofructokinasephosphofructokinaseinhibited by ATP and citrate

pyruvate kinasepyruvate kinaseinhibited by ATP

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Regulation of glycolysisRegulation of glycolysis

glucose

glucose 6-phosphate

fructose 6-phosphate

fructose 1,6-bisphosphate

phosphoenolpyruvate

pyruvate

feedback inhibitionhexokinasehexokinase

phosphofructokinasephosphofructokinase

pyruvate kinasepyruvate kinase

Documents

1 Metabolism of Carbohydrates The Energy Metabolism of Glucose Entry of other Carbohydrates into Glycolysis Pyruvate Metabolism Biosynthesis of Carbohydrates