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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
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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Entry of other carbohydratesinto glycolysis
Entry of other carbohydratesinto glycolysis
DisaccharidesDisaccharides
maltose + H2O 2 glucose
sucrose + H2O fructose + glucose
lactose + H2O glucose + galactose
maltase
invertase(bacteria)
sucrase(animals)
lactase
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Entry of other carbohydratesinto glycolysis
Entry of other carbohydratesinto glycolysis
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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Entry of other carbohydratesinto glycolysis
Entry of other carbohydratesinto glycolysis
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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Entry of other carbohydratesinto glycolysis
Entry of other carbohydratesinto glycolysis
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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GluconeogenesisGluconeogenesis
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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GluconeogenesisGluconeogenesis
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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GluconeogenesisGluconeogenesis
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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GluconeogenesisGluconeogenesis
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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GluconeogenesisGluconeogenesis
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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GluconeogenesisGluconeogenesis
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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GluconeogenesisGluconeogenesis
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
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