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Food is…..
……….. Energy !
Review concepts
Catabolism: Metabolic reaction pathways that break down
food molecules and release biochemical energy.
Anabolism: Metabolic reactions that build larger biological
molecules from smaller pieces.
** Refer to sections 21.1 and 21.2
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Review concepts
Many metabolic reactions are redox
Reactions.
Coenzymes continuously cycle between
their oxidized and reduced forms.
Ex: NAD+ and NADH/H+
NADP+ and NADPH+/H+
FAD/FADH2
Review concepts
Exergonic and Endergonic reactions:
∆G = ∆H – T∆S
Spontaneous reactions release free energy,
which is available to do work. Exergonic reactions have
A negative G value. Endergonic reactions are a nonspontaneous
reaction or process that absorbs free energy and has a positive ∆G.
** Refer to sections 21.1 and 21.2
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What is Acetyl-S-CoA ?
An important metabolic intermediate for breakdown of
all classes of food.
It is a thiol and can react with acids to form a thioester.
Aids in transfer of acetyl groups, (i.e acetyltransferase )
23.2 Glucose Metabolism: An Overview
•
•
•
When glucose enters a cell from the bloodstream, it is
immediately converted to glucose 6-phosphate.
Once this phosphate is formed, glucose is trapped within the
cell because phosphorylated molecules cannot cross the cell
membrane.
Like the first step in many metabolic pathways, the formation
of glucose-6-phosphate is highly exergonic and not reversible
in the glycolytic pathway, thereby committing the initial
substrate to subsequent reactions.
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Glucose-6-phosphate can enter the pentose phosphate
pathway. This multistep pathway yields two products
of importance to our metabolism
One is a supply of the coenzyme NADPH, a
reducing agent that is essential for various
biochemical reactions.
The other is ribose 5-phosphate, which is
necessary for the synthesis of nucleic acids (DNA
and RNA).
When energy is needed, glucose 6-phosphate
undergoes glycolysis to pyruvate and then to acetyl-S-coA,
which enters the citric acid cycle.
23.3 Glycolysis
Step 1. Conversion of Glucose Æ Glucose-6-phosphate
Step 2. Glucose-6-phosphate Æ Pyruvate (via several steps of
Glycolysis pathway)
Step 3. Pyruvate Æ Acetyl-ScoA
Following: Glucose to Acetyl-ScoA (formation of the –6-phos
phate is highly exergonic, and irreversible)
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23.3 Glycolysis
Glycolysis is a series of 10 enzyme-catalyzed reactions
that break down glucose molecules.
The net result of glycolysis is the production of two
pyruvate molecules, two ATPs, and two NADH/H+s.
Glycolysis
• Steps 1-5 of glycolysis break one glucose molecule down into
two D-glyceraldehyde 3-phosphate fragments.
• An investment of 2 ATP molecules is required.
• Steps 6-10 occur twice for each glucose that enters in at step 1.
• Steps 6-10 produce: 2 pyruvates, 4 ATPs, 2 NADH/H+ per
glucose molecule
For complete reactions of glucose to pyruvate: Figure 23.3, page
720 of text
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23.5 What happens to Pyruvate?
• A decarboxylation reaction
• NAD+ reduces to NADH
• S-CoA is dehydrogenated
•Why do we call this an oxidation?
Structure of the multienzyme complex Pyruvate
Dehydrogenase, has a core
of 24 proteins.
What happens to Pyruvate?
Anaerobic: In the absence of oxygen.
If electron transport slows because of insufficient oxygen,
NADH concentration increases, NAD+ is in short supply,
and glycolysis cannot continue.
An alternative way to reoxidize NADH is essential because
glycolysis, the only available source of fresh ATP, must
continue. The reduction of pyruvate to lactate solves the
problem.
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21.7 What happens to Acetyl-SCoA?
21.7 Citric Acid Cycle (a.k.a TCA cycle, Krebs cycle)
-Takes place in mitochondria.
The acetyl group is converted
To CO2 (redox?)
-Cyclic pathway, why?
Explain the reaction from the Citric
Acid cycle and the enzyme class that will act as
catalysts.
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Net result of the Citric Acid
Cycle
The net result of the citric acid cycle is:
-Production of four reduced coenzyme
molecules, 3 NADH and 1 FADH2
-Conversion of an acetyl group to two
CO2 molecules
-Production of one energy-rich
molecule (GTP)
The eight steps of the citric acid cycle are shown in
greater detail on Section 21.8 of your text.
23.7 Regulation of Glucose Metabolism and
Energy Production
• Normal blood glucose
concentration a few hours after a
meal ranges roughly from 65 to
110 mg/dL.
• Hypoglycemia: Lower-than
normal blood glucose
concentration.
• Hyperglycemia: Higher-than
normal blood glucose
concentration.
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•
•
•
Two hormones from the pancreas have the major
responsibility for blood glucose regulation.
The first, insulin, is released when blood glucose
concentration rises.
The second hormone, glucagon, is released when blood
glucose concentration drops.
23.8 Metabolism in Fasting and Starvation
• The metabolic changes in the absence of food begin with a
gradual decline in blood glucose concentration
accompanied by an increased release of glucose from
glycogen.
• All cells contain glycogen, but most is stored in liver cells
(about 90 g in a 70-kg man) and muscle cells (about 350 g
in a 70-kg man). Free glucose and glycogen represent less
than 1% of our energy reserves and are used up in 15–20
hours of normal activity (3 hours in a marathon race).
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• During the first few days of
starvation, protein is used
up at a rate as high as 75
g/day.
• Lipid catabolism is
mobilized, and acetyl-SCoA
molecules derived from
breakdown of lipids
accumulate.
• Acetyl-SCoA begins to be
removed by a new series of
metabolic reactions that
transform it into ketone
bodies.
As starvation continues, the brain and other tissues are able to
switch over to producing up to 50% of their ATP from
catabolizing ketone bodies instead of glucose. By the 40th day
of starvation, metabolism has stabilized at the use of about 25 g
of protein and 180 g of fat each day. So long as adequate water
is available, an average person can survive in this state for
several months; those with more fat can survive longer.
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23.9 Metabolism in Diabetes Mellitus
• Diabetes mellitus: A chronic condition due to either
insufficient insulin or failure of insulin to activate crossing
of cell membranes, by glucose.
• The symptoms by which diabetes is usually detected are
excessive thirst accompanied by frequent urination,
abnormally high glucose concentrations in urine and blood,
and wasting of the body despite a good diet. These
symptoms result when available glucose does not enter
cells where it is needed.
• Type II diabetes is thought to result when cell membrane
receptors fail to recognize insulin. Drugs that increase either
insulin or insulin receptor levels are an effective treatment
because more of the undamaged receptors are put to work.
• Type I diabetes is classified as an autoimmune disease, a
condition in which the body misidentifies some part of itself as
an invader. Gradually, the immune system wrongly identifies
pancreatic beta cells as foreign matter, develops antibodies to
them, and destroys them. To treat Type I diabetes, the missing
insulin must be supplied by injection.
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Blood glucose concentration in
glucose tolerance test
for normal and diabetic individuals.
Metabolism of
TriAcylGlycerols
Pathways that break down
molecules (catabolism) are
shown in light brown, and
synthetic pathways
(anabolism) are shown in
blue. Connections to other
pathways or intermediates
of metabolism are shown in
green.
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25.5 Oxidation of Fatty Acids
•
•
•
•
Once a fatty acid enters the cytosol of a cell that needs
energy, three successive processes must occur.
1. Activation: The fatty acid must be activated by
conversion to fatty acyl-SCoA. Some energy from ATP
must initially be invested in converting the fatty acid to
fatty acyl-SCoA, a form that breaks down more easily.
2. Transport: The fatty acyl-SCoA must be transported into
the mitochondrial matrix where energy generation will occur.
Carnitine, a transmembrane protein found only in the
mitochondrial membrane, specifically moves fatty acyl-SCoA
across the membrane into the mitochondria.
3. Oxidation: The fatty acyl-SCoA must be oxidized by
enzymes in the mitochondrial matrix to produce acetyl-SCoA
plus the reduced coenzymes to be used in ATP generation.
The oxidation occurs by repeating the series of four reactions
which make up the β-oxidation pathway.
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β-Oxidation refers to the oxidation of the carbon atom β to the
thioester linkage in two steps of the pathway.
• STEP 1: The first β−oxidation: The oxidizing agent FAD
removes hydrogen atoms from the carbon atoms α and β to
the C=O group in the fatty acyl-SCoA, forming a carbon–
carbon double bond.
• STEP 2: Hydration: A water molecule adds across the newly
created double bond to give an alcohol with the –OH group on
the β-carbon.
• STEP 3: The second β−oxidation: NAD+ is the oxidizing
agent for conversion of the β−ΟΗ group to a carbonyl group.
• STEP 4: Cleavage to remove an acetyl group: An acetyl
group is split off and attached to a new coenzyme A molecule,
leaving behind an acyl-SCoA that is two carbon atoms shorter.
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The four steps of the β-oxidation pathway:
25.6 Energy from Fatty Acid Oxidation
• The total energy output from fatty acid catabolism is
measured by the total number of ATPs produced. Current
best estimates are that 2.5 ATPs result from each NADH
and 1.5 ATPs from each FADH2.
• The β-oxidation pathway produces 1 NADH and 1 FADH2
or 4 ATPs per cycle.
• Each acetyl-SCoA produces 3 NADH, 1 FADH2 and 1
ATP or 10 ATPs per acetyl-SCoA.
• Lauric acid, CH3(CH2)10COOH, has 12 carbons.
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• After initial activation (-2 ATP), five β-oxidations (5x4 ATP =
+20 ATP) will change lauric acid into 6 acetyl-SCoA
molecules (6x10 ATP = + 60 ATP). The total energy yield is
78 ATP per lauric acid.
• 1 mole (200g) lauric acid yields 78 moles ATP
• 1 mole (180g) glucose yields 30-32 moles ATP
• Fats and oils yield 9 Calories per gram
• Carbohydrates yield 4 Calories per gram
• Each gram of glycogen can hold as much as 2 grams of water
so fats are almost 7 times more energy dense than
carbohydrates in the body.
Practice questions section
C6H12O6 + 6 O2 → 6 CO2 + 6 H2O ∆G = – 686 kcal/mol
The oxidation of glucose, shown above, is an important reaction in the
body. This reaction is
1.
2.
3.
4.
endergonic, as represented by energy diagram (a).
exergonic, as represented by energy diagram (a).
endergonic, as represented by energy diagram (b).
exergonic, as represented by energy diagram (b).
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In the pathways for the digestion of food and the production of
biochemical energy, the oxidation of Acetyl-SCoA occurs in
1. stage 1: digestion.
2. stage 2: Acetyl-SCoA
production.
3. stage 3: citric acid cycle.
4. stage 4: ATP production.
21.5 Write the products of Hydrolysis:
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What is the general class of enzyme that catalyzes this process ?
21.24 In which step is a coenzyme
needed? Identify the coenzyme. b)
In which step is carbon dioxide
evolved and a hydrogen ion added?
c) Which of the structures shown
can be described as a beta-keto
acid?
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Normal metabolism as well as unusual stresses
can produce reactive oxygen species capable of injuring cells.
In the induction stage of the Atkins diet ketosis is induced in
which blood glucose levels drop and blood ketone bodies
increase. Which of the compounds below are ketone bodies?
OH
O
|
||
CH3–CH–CH2–C–O–
3-Hydroxybutyrate
O
O
||
||
CH3–C–CH2C–O–
Acetoacetate
1.
2.
3.
4.
Acetone
Acetone and acetoacetate
3-Hydroxybutyrate
All of the above
O
||
CH3–C–CH3
Acetone
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When blood glucose levels rise following a meal, which of the
following events occurs first?
1.
2.
3.
4.
Blood levels pass through normal to below normal.
Glycolysis occurs to replenish the ATP supplies.
Glucose is absorbed by the cells.
Insulin levels rise.
The conjugate base of the bile acid cholic acid and cholesterol are
shown below. To what general class of compounds do they
belong?
1.
2.
3.
4.
Eicosanoids
Fatty acids
Glycolipids
Steroids
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