Transcript Chem 150 Unit 12

Chem 150
Unit 12 - Metabolism
Metabolism is the sum total of all the reactions that take place
in a living cell. These reactions are used to extract energy and
materials form the environment (catabolism), and to use this
energy and these materials to produce new molecules
(anabolism ) that will sustain the cell and allow it to to
propagate itself. There are literally thousands of reactions
involved in metabolism, but we will focus our attention on a
core set of reactions that will allow us to understand some of
core principals that define metabolism.
Introduction
In this unit we will look at some themes which define
metabolism.
• There are literally thousands of chemical reactions that
take place in a living cell
• If you wrote the chemical equations for all of these
reactions down on a single piece of paper, it would look
something like this:
View the Metabolic Chart
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Introduction
Some of the themes include:
• The reactions are arranged into pathways, where the
product for one reaction is the reactant (substrate) for the
next reaction.
• The arrangement of reactions looks very much like a wiring diagram,
•
•
•
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but instead of tracing the flow of electrons, the metabolic pathways
trace the flow of atoms and molecules.
Every chemical reaction in metabolism is catalyzed by an
enzyme.
• The enzymes are used like valves to control the flow of material
through the pathways.
Nonspontaneous reactions are driven by coupling them to
spontaneous reactions.
An outside source of energy is needed drive metabolism
Pathways, Energy, and Coupled Reactions
Metabolic reactions are arranged in pathways
• The product of one reaction is the substrate for the next
reaction in the pathway.
• There are different topologies for metabolic pathways.
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Pathways, Energy, and Coupled Reactions
The molecules that are placed along the pathway are the
intermediates in the reactions
• Other reactants and products are usually represented by
side arrows
• This reaction
equation could also be written asaldehyde
alcohol
NAD+
CH3
CH2
CH3
alcohol dehydrogenase
enzyme
OH
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O
OH
ethanol
CH3 CH2
ethanol
NADH + H+
C
H
ethanal
(acetaldehyde)
O
+
NAD+
CH3 C H
acetaldehyde
+
NADH + H+
Pathways, Energy, and Coupled Reactions
When two reactions are connected through a common
intermediate, they are said to be coupled.
• The coupling of reactions allows spontaneous reactions to
drive nonspontaneous reactions.
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Pathways, Energy, and Coupled Reactions
The phosphorylation of ADP can be coupled to the
dephosphorylation of 1,3-Bisphosphoglycerate:
O
O
C
O
P
O
O
C
OH
O
O
H C
+
OH
H2O
H C
O
CH2
O
P
O
O
O
1,3-bisphosphoglycerate
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+
OH
CH2
O
P
HO
P
O
O
O
3-phosphoglycerate
Pi
O
Gº = -11.8 kcal/mol
Pathways, Energy, and Coupled Reactions
The phosphorylation of ADP can be coupled to the
dephosphorylation of 1,3-Bisphosphoglycerate:
ADP
+
Pi
1,3-bisphosphoglycerate + H2O
ADP + Pi + 1,3-bisphosphoglycerate + H2O
ATP
+
Gº = + 7.3 kcal/mol
H2O
3-phosphoglycerate
+
Gº = -11.8 kcal/mol
Pi
ATP + H2O + 3-phosphoglycerate + Pi
OH
ADP + 1,3-bisphosphoglycerate
ATP + 3-phosphoglycerate
CH3 CH2
ethanol
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Gº = -4.5 kcal/mol
Overview of Metabolism
Metabolism
• The sum of all reactions that take place in a living
organism.
View the Metabolic Chart
Metabolism = Catabolism + Anabolism
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•
Catabolism - larger molecules are broken down into
smaller ones in a process that usually releases energy
•
Anabolism - larger molecules are made from small ones in
a process the usually requires energy
Overview of Metabolism
One of the common links between catabolism and anabolism
is ATP.
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ATP is used to shuttle chemical energy from catabolism to
anabolism.
Overview of Metabolism
One of the common links between catabolism and anabolism
is ATP.
•
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ATP is used to shuttle chemical energy from catabolism to
anabolism.
Overview of Metabolism
•
This is done by coupling the spontaneous reactions in
catabolism to the phosphorylation of ADP to produce ATP:
ADP + Pi
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ATP +
H2O
² G = +7.3 kcal/mol
And then coupling the unfavorable reactions in anabolism
to the hydrolysis of ATP:
ATP +
H2O
ADP + Pi
² G = -7.3 kcal/mol
ATP +
H2O
AMP + PPi
² G = -7.6 kcal/mol
Overview of Metabolism
The biological oxidation/reduction agents NAD+ and FAD are
also used to shuttle energy from the favorable oxidations that
take place in catabolism, to the unfavorable reductions that
take place in anabolism
catabolism
anabolism
A is oxidized
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B is reduced
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Overview of Metabolism
Catabolism
• Occurs in stages.
• Occupies the center of
the metabolic chart.
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Overview of Metabolism
The reactions from Acetyl-Co and below require molecular
oxygen (O2).
• These reactions take place in a specialized organelle
called the mitochondria.
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Digestion
Digestion is the first stage of metaboism in which large
molecule are broken done in small molecules that can be
absorbed into the blood in the small intestine.
• Most of these reactions are hydrolysis reactions
• Proteins are hydrolyzed in to amino acids
• Polysaccharides are hydrolyzed into monosaccharides
• Triglycerides are hydrolyzed into fatty acids and glycerol.
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Glycolysis
Glycolysis is a series of 10 coupled reactions
• The pathway starts with glucose that comes into a cell from
the blood and is immediately phosphorylated to glucose-6phosphate.
• The phosphorylation traps the glucose in the cell.
• The pathway then goes on to split (lyse) the the 6-carbon
glucose molecule into two 3-carbon molecules and to
oxidize these to α-keto acids (Pyruvic acid).
• The energy released in the pathway is used to produce two
types of energy rich molecules:
• Two molecules of ADP are phosphorylated to ATP.
• Two molecules of NAD+ are reduced to NADH/H+.
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Glycolysis
Step 1: Glucose is brought
into the cell and
phosphorylated.
• The phosphorylation is
coupled to the
hydrolysis of ATP.
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Glycolysis
Step 2: Glucose-6phosphate (an
aldohexose) is isomerized
to fructose-6-phosphate (a
ketohexose).
• This reaction occurs
near equilibrium, which
allows it to go in either
direction.
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Glycolysis
Step 3: Fructose-6phosphate is
phosphorylated to
fructose-1,6-bisphosphate.
• This reaction is coupled
to the hydrolysis of ATP.
• This sets things up for
the cleavage, which
occurs in the next step.
• So far 2 ATP’s have
been used instead of
produced.
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Glycolysis
Step 4: Fructose-1,6bisphosphate splits into two
three carbon
monosaccharides
• Glyceraldehyde-3-phophate.
• Dihydroxyacetone phosphate
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Glycolysis
Step 5: Dihydroxyacetone phosphate is isomerized to
glyceraldehyde-3-phosphate.
• The last five reactions in glycolysis start with
glyceraldehyde-phosphate.
• The remaing reactions will couple the oxidation of
glyceraldhyde-3-phosphate to the production of ATP and
NADH/H+.
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Glycolysis
Step 6: Glyceraldehyde-3phosphate is oxidized to 1,3Bisphosphoglycerate.
• The oxidation of the
aldehyde to an acid is
coupled to the reduction of
NAD+ to NADH/H+ and the
phosphorylation of the acid
to a mixed phosphate
anhydride.
• The hydrolysis of a
phosphate anhydride has
a large negative ΔG.
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Glycolysis
Step 7: The hydrolysis of the
phosphate from 1,3bisphosphoglycerate is
coupled to the
phosphorylation of ADP to
generate ATP
• Since two 1,3bisphosphoglycerates are
produced per glucose
molecule, the two ATP’s
that were invested in the
first part of glycolysis have
now been recovered.
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Glycolysis
The remaining three steps will convert the phosphate ester in
3-phosphoglycerate into a phosphate whose hydrolysis can
be coupled to the phosphorylation of ADP to produce ATP.
• Phosphate esters do not have a large enough negative ΔG
to be coupled to the phosphorylation of ADP.
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Glycolysis
Step 8: 3-Phosphoglycerate
is isomerized to 2phosphoglycerate.
• The phosphate ester is
moved form carbon 3 to
carbon 2.
• Like most isomerization
reactions, this reaction can
go in either direction.
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Glycolysis
Step 9: 2-Phosphoglycerate
is dehydrated to form
phosphoenolpyruvate.
• The dehydration of the
alcohol produces a double
bond between carbons 2
and 3.
• This produces a
phosphate with a large
negative free energy for
hydrolysis, which can now
be coupled to the
phosphorylation of ADP.
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Glycolysis
Step 10: The hydrolysis of the
phosphate from
phosphoenolpyruvate is
coupled to the phosphorylation
of ADP.
• The hydroxyl group that is
produced next to the carboncarbon double-bond
spontaneously isomerizes to
a ketone.
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Glycolysis
The net reaction for coupling all ten steps in glycolysis:
• The energy released in the pathway is used to produce two
types of energy rich molecules:
CH OH
• Two
molecules of ADP are phosphorylated to ATP.
O O
O
+
+.
• Two molecules +of 2NAD
are reduced
to
NADH/H
NAD + 2 ADP + 2 P
2 CH C C OH + 2NADH/H + 2 ATP
2
+
OH
i
3
OH
OH
OH
glucose
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pyruvate
+
Glycolysis
Fates of pyruvate when molecular oxygen cannot be used to
reoxidize the NADH/H+ back to NAD+.
• The fermentation pathways provide away of reoxidizing
NADH/H+ back to NAD+, so that it can be used to keep
glycolysis going.
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Gluconeogenesis
Gluconeogenesis is the synthesis
of glucose from pyruvate
• It uses 7 out of the 10
reactions from glycolysis.
• The remaining three have too
large a negative free energy to
be reversed.
• These include steps
‣ 1, 3 and 10
• Alternative reactions are used
to get around these falls.
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Glycogen Metabolism
When glucose is not needed to meet energy needs, it can be
stored as the polysaccharide glycogen and used for future
energy needs.
• The liver and the muscles are where glycogen is
synthesized and stored.
• The muscles store it for future muscular activity.
• The liver stores it to help regulate blood glucose levels.
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Glycogen Metabolism
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Citric Acid Cycle
If an organism can utilize molecular oxygen to accept
electrons from the reduced nucleotides NADH/H+ and FADH2,
then the pyruvate from glycolysis can be completely oxidized
to CO2 and H2O.
• These reactions occur within a cellular organelle called the
mitochondria.
• The first step in the complete oxidation is the
decarboxylation of pyruvate to produce Acetyl-S-CoA.
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Citric Acid Cycle
The Acetyl-CoA is fed into the citric acid cycle, where its two
carbons are oxidized to CO2.
• In the process
• 3 more NAD+ are reduced to NADH/H+
• 1 FAD is reduced to FADH2
• 1 GDP is phosphorylated to GTP
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Citric Acid Cycle
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Citric Acid Cycle
The net reaction for coupling all 8 steps in glycolysis:
O
CH3 C
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CoA
+
3 NAD+ + FAD +
GDP + Pi
2 CO2 + CoA + 3 NADH/H+ + FADH2 + GTP
Electron Transport Chain and
Oxidative Phosphorylatioin
The reoxidation of the NADH/H+ to NAD+ and FADH2 to FAD
using molecular oxygen (O2) as the oxidizing agent, is carried
out by the electron transport chain.
• The electron transport chain is located within the inner
membrane of mitochondria.
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Electron Transport Chain and
Oxidative Phosphorylatioin
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Electron Transport Chain and
Oxidative Phosphorylatioin
The reoxidation of the NADH/H+ to NAD+ and FADH2 to FAD
using molecular oxygen (O2) as the oxidizing agent, is carried
out by the electron transport chain.
• The energy released in the reoxidation is coupled to the
synthesis of ATP from ADP and Pi by the enzyme ATP
synthase.
• The coupling involves the creation of a hydrogen ion concentration
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gradient across the inner mitochondrial membrane.
The energy for synthesizing the ATP comes from allowing the the
hydrogen ions to flow back across the membrane.
The End