Download Document

Metabolism of Carbohydrates
The Energy Metabolism of Glucose
Entry of other Carbohydrates into
Glycolysis
Pyruvate Metabolism
Biosynthesis of Carbohydrates
Regulation of Carbohydrate Metabolism
1
Metabolism 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:
brain
erythrocytes
many bacteria
2
Carbohydrate metabolism
Glycolysis
The main pathway for glucose oxidation.
It forms pyruvate anaerobically.
Phosphogluconate pathway
An auxiliary route for glucose oxidation in
animals. It produces ribose-5-phosphate.
Gluconeogenesis
Pathway for the synthesis of glucose from
pyruvate.
3
Energy metabolism of glucose
Lactate
Disaccharides
gluconeogenesis
anabolism
Glycogen (animals)
Starch (plants)
Glucose
catabolism
phosphogluconate
pathway
Pyruvate
glycolysis
ATP +
NADH + H+
anaerobic,muscles
aerobic
Acetyl CoA
anaerobic,yeast
Ethanol
Ribose-5-phosphate
+ NADPH + H+
4
Glycolysis
First stage of carbohydrate catabolism.
Simple sugars are broken down to pyruvate.
Anaerobic process - no oxygen needed.
All life uses this process.
Requires
glucose, 2 ADP, 2 ATP, 2 NAD+, 2 PO4=
10 different enzymes
5
First five reactions of glycolysis
glucose
ATP
ADP
ATP
ADP
glucose-6-P
fructose-6-P
6 carbon
stage
Requires
energy
fructose-1,6-bisP
glyceraldehyde-3-P
dihydroxyacetone-P
6
Reactions of glycolysis
NAD+
NADH + H+
ADP
ATP
glyceraldehyde-3-P
1,3-bisphosphoglycerate
3-phosphoglycerate
ADP
ATP
Pi
3 carbon
stage
Double this
2-bisphosphoglycerate
since two
H2O
pyruvate
phosphoenolpyruvate
are made.
pyruvate
7
Overall glycolysis
glucose 2 ADP + 2 PO4= + 2 NAD+
10 enzymes
2 pyruvate + 2 NADH + 2 H2O + 2 ATP
Net energy produced is 2 ATP
In addition, the two pyruvate can go on to the
citric acid cycle to produce more energy.
8
Entry of other carbohydrates
into glycolysis
Dietary carbohydrates
Polysaccharides
Starches and glycogen are hydrolyzed
to glucose by amylase in the mouth.
Disaccharides
Maltose, sucrose and lactose. Each is
hydrolyzed to a different pair of
monosaccharides.
9
Entry of other carbohydrates
into glycolysis
Disaccharides
maltase
maltose + H2O
sucrose + H2O
lactose + H2O
2 glucose
invertase
(bacteria)
sucrase
(animals)
lactase
fructose + glucose
glucose + galactose
10
Entry of other carbohydrates
into glycolysis
Fructose
Enters glycolysis by two different
pathways depending on the tissue.
Skeletal muscles
The 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.
11
Entry of other carbohydrates
into glycolysis
Fructose
Liver Cells
They have another enzyme, fructokinase.
• It has a stronger affinity for fructose.
• It catalyzes phosphoryl group transfer
from ATP to produce fructose-1phosphate.
An aldolase-type cleavage and additional
phosphorylation must also occur.
12
Entry of other carbohydrates
into glycolysis
Galactose
Five reactions are required to transform it
into glucose-6-phosphate.
Galactose
Glucose-6-phosphate
Phosphoglucomutase
galactokinase
Galactose-1-phosphate
galactose-1phosphate uridyl
transferase
UDP-galactose
Glucose-1-phosphate
UDP-galactose
-4-epimerase
UDP-glucose
pyrophosphorylase
UDP-glucose
13
Pyruvate 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.
Fermentation - subsequent processing
under anaerobic conditions.
14
Fermentation
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.
15
Lactate fermentation
Lactate
Produced by muscles when the body can’t
supply enough oxygen.
pyruvate
NADH + H+
lactate
NAD+
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.
16
Alcohol fermentation
Used by anaerobic bacteria to obtain
additional energy from glucose.
pyruvate
pyruvate
decarboxylase
NADH + H+
NAD+
acetaldehyde + CO2
alcohol
dehydrogenase
ethanol
17
Biosynthesis of carbohydrates
Gluconeogenesis
Synthesis 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.
18
Biosynthesis of carbohydrates
Skeletal muscles
Glycogen
glucose-6-P
exercise
glucose-6-P
Blood
Liver
Glycogen
glucose-6-P
rest
glucose
glucose-6-P
pyruvate
pyruvate
lactate
lactate
Muscles lack enzyme needed to convert pyruvate to
glucose-6-P. Must be sent to liver.
19
Gluconeogenesis
Phosphoenolpyruvate
Stage I
Oxaloacetate
Pyruvate
Lactate
Malate
mitochondria
Pyruvate
Pyruvate
Malate
Phosphoenol
pyruvate
Pyruvate
Oxaloacetate
Oxaloacetate
20
Gluconeogenesis
Glycogen
UDP-glucose
Stage III
ATP
Glucose-1-phosphate + UDP
Glucose-6-phosphate
Glucose
Fructose-6-phosphate
Pi
HO
2
ATP
P
i
HO
2
Stage II
Fructose-1,6-bisphosphate
Glyceraldehyde-3-phosphate
3-Phosphoglycerate
2-Phosphoglycerate
Phosphoenolpyruvate
21
Gluconeogenesis
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
10. PEP + ADP
fructose-1,6
-bisphosphate + ADP
pyruvate + ATP
22
Gluconeogenesis
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.
23
Gluconeogenesis
Bypass I. Overall reaction
pyruvate +
ATP + GTP
phosphoenolpyruvate +
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.
24
Gluconeogenesis
Bypass II
Fructose-1,6-bisphosphate
Fructose-6-phosphate
Phosphofructokinase
• 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.
25
Gluconeogenesis
glycolysis
ATP
phosphofructokinase
Pi
fructose-1,6bisphosphatase
H2O
gluconeogenesis
Fructose-6-phosphate
Fructose-1,6-bisphosphate
26
Gluconeogenesis
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-6phosphatase
glucose-6-phosphate + H2O
glucose + Pi
27
Synthesis of disaccharides
and polysaccharides
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.
28
Activation of glucose and galactose
Nucleotide diphosphate sugars (NDP sugars)
Used primarily to mark sugars to be set aside
for bisynthetic purposes.
Synthesis of NDP-glucose.
NTP + glucose-1-phosphate
NDP-glucose + PPi
NTP = nucleotide triphosphate, ATP, UTP or GTP
Enzyme = UDP-glucose pyrophosphorylase
ADP-glucose pyrophosphorylase
GDP-glucose pyrophosphorylase
29
Synthesis of UDP-galactose
Two possible routes
Isomerization of UDP-glucose
UDP-glucose
UDP-galactose
Enzyme = UDP-glucose-4-epimerase
Exchange of UDP
galactose-1-phosphate + UDP-glucose
UDP-galactose +
glucose-1-P
Enzyme = glactose-1-phosphate uridyl transferase
30
Synthesis 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
31
Synthesis 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
32
Synthesis 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
33
Synthesis of sucrose
Sucrose is present in most fruits and
vegetables. It is produced by a two step
process.
UDP-glucose + fructose-6-phosphate
sucrose-6phosphate
synthase
H2O
phosphatase
sucrose-6-phosphate + UDP
sucrose + Pi
34
Synthesis 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
35
Regulation of glycolysis
As with all metabolic pathways, glycolysis is
under constant control by the body.
The process is regulated by three enzymes:
hexokinase
inhibited by glucose 6-phosphate
phosphofructokinase
inhibited by ATP and citrate
pyruvate kinase
inhibited by ATP
36
Regulation of glycolysis
feedback inhibition
glucose
hexokinase
glucose 6-phosphate
fructose 6-phosphate
phosphofructokinase
fructose 1,6-bisphosphate
phosphoenolpyruvate
pyruvate
pyruvate kinase
37