Transcript Metabolism and Energy Production

Chapter 24 Metabolic Pathways
for Lipids and Amino Acids
24.1
Digestion of Triacylglycerols
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1
Digestion of Fats
(Triacylglycerols)
In the digestion of fats (triacylglycerols),
 Bile salts break fat globules into smaller particles
called micelles in the small intestine.
 Pancreatic lipases hydrolyze ester bonds to form
monoacylglycerols and fatty acids, which recombine
in the intestinal lining.
 Fatty acids bind with proteins forming lipoproteins to
transport triacylglycerols to the cells of the heart,
muscle, and adipose tissues.
2
Digestion of Triacylglycerols
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Fat Mobilization
Fat mobilization
 Breaks down
triacylglycerols in adipose
tissue.
 Forms fatty acids and
glycerol.
 Hydrolyzes fatty acid
initially from C1 or C3 of
the fat.
triacylglycerols + 3 H2O
glycerol + 3 fatty acids
4
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Metabolism of Glycerol
Glycerol from fat digestion
 Adds a phosphate from ATP to form glycerol-3phosphate.
 Undergoes oxidation of the –OH group to
dihydroxyacetone phosphate.
 Becomes an intermediate used in glycolysis and
gluconeogenesis.
Glycerol + ATP + NAD+
dihydroxyacetone phosphate + ADP + NADH + H+
5
Oxidation of Glycerol
glyerol
kinase
H2C OH
H2C OH
C OH + ATP
C OH O
+
ADP
H2C O P O-
H2C OH
Oglycerol
glycerol-3-phosphate
NAD+
dehydrogenase
NADH + H+
H2C OH
C O O
dihydroxyacetone phosphate
H2C O P OOglycolysis
gluconeogenesis
6
Learning Check
Give answers for the following questions on fat
digestion.
1. What is the function of bile salts in fat digestion?
2. Why are the triacylglycerols in the intestinal lining
coated with proteins to form chylomicrons?
3. How is glycerol utilized?
7
Solution
1. What is the function of bile salts in fat digestion?
Bile salts break down fat globules allowing
pancreatic lipases to hydrolyze the triacylglycerol.
2. Why are the triacylglycerols in the intestinal lining
coated with proteins to form chylomicrons?
The proteins coat the triacylglycerols to make water
soluble chylomicrons that move into the lymph and
bloodstream.
3. How is glycerol utilized?
Glycerol adds a phosphate and is oxidized to an
intermediate of the glycolysis and gluconeogenesis
pathways.
8
Chapter 24 Metabolic Pathways
for Lipids and Amino Acids
24.2
Oxidation of Fatty acids
24.3
ATP and Fatty Acid Oxidation
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Fatty Acid Activation
Fatty acid activation
 Allows the fatty acids in the cytosol to enter the
mitochondria for oxidation.
 Combines a fatty acid with CoA to yield fatty acyl
CoA that combines with carnitine.
Fatty acyl
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Transport of Fatty Acyl CoA
 Fatty acyl-CoA forms fatty acyl-carnitine that
transports the fatty acyl group into the matrix.
 The fatty acyl group recombines with CoA for
oxidation.
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Summary of Fatty Acid Activation

Fatty acid activation is complex, but it regulates
the degradation and synthesis of fatty acids.
Fatty acyl
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Beta-Oxidation of Fatty Acids
Fatty acyl CoA undergoes
β oxidation in a cycle of four
 
reactions.
In reaction 1, oxidation
 Removes H atoms from the
 and  carbons.
 Forms a trans C=C bond.
 Reduces FAD to FADH2.
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Beta-Oxidation of Fatty Acids
In reaction 2 of
 
β oxidation, hydration
 Adds water across
the trans C=C
bond.
 Forms a hydroxyl
group (—OH) on
the  carbon.
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Beta-Oxidation of Fatty Acids
In reaction 3 of β
oxidation, a second
oxidation
 Oxidizes the
hydroxyl group.
 Forms a keto
group on the 
carbon.

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Beta()-Oxidation of Fatty Acids
In Reaction 4 of βoxidation, acetyl CoA
is cleaved
 By splitting the bond
between the  and
 carbons.
 To form a shortened
fatty acyl CoA that
repeats steps 1 - 4
of -oxidation.
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Learning Check
Match the reactions of -oxidation with each:
1) oxidation 1
2) hydration
3) oxidation 2
4) acetyl CoA cleaved
A.
B.
C.
D.
E.
Water is added.
FADH2 forms.
A two-carbon unit is removed.
A hydroxyl group is oxidized.
NADH forms.
17
Solution
Match the reactions of -oxidation with each:
1) oxidation 1
2) hydration
3) oxidation 2
4) acetyl CoA cleaved
A.
B.
C.
D.
E.
2
1
4
3
3
Water is added.
FADH2 forms.
A two-carbon unit is removed.
A hydroxyl group is oxidized.
NADH forms.
18
Beta()-Oxidation of Myristic
(C14) Acid
19
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Beta()-Oxidation of Myristic
(C14) Acid (continued)
C14
6
cycles
7 Acetyl
CoA
20
Fatty Acid Length and
-Oxidation
The length of a fatty acid
 Determines the number of oxidations
 Determines the total number of acetyl CoA groups.
Carbons in
Acetyl CoA
-Oxidation Cycles
Fatty Acid
(#C/2)
(#C/2 –1)
12
6
5
14
7
6
16
8
7
18
9
8
21
Learning Check
A. The number of acetyl CoA groups produced by
the complete -oxidation of palmitic acid (C16 ):
1) 16
2) 8
3) 7
B. The number of oxidation cycles to completely
oxidize palmitic acid (C16 ):
1) 16
2) 8
3) 7
22
Solution
A. The number of acetyl CoA groups produced by
the complete -oxidation of palmitic acid (C16 ):
2) 8
(16 C/2 = 8)
B. The number of oxidation cycles to completely
oxidize palmitic acid (C16 ):
3) 7
(16 C/2 -1 = 7)
23
ATP and -Oxidation
Activation of a fatty acid requires
2 ATP
One cycle of oxidation of a fatty acid produces
1 NADH
3 ATP
1 FADH2
2 ATP
Acetyl CoA entering the citric acid cycle produces
1 Acetyl CoA
12 ATP
24
ATP for Lauric Acid C12
ATP production for lauric acid (12 carbons):
Activation of lauric acid
-2 ATP
6 Acetyl CoA
6 acetyl CoA x 12 ATP/acetyl CoA
72 ATP
5 Oxidation cycles
5 NADH x 3ATP/NADH
5 FADH2 x 2ATP/FADH2
Total
15 ATP
10 ATP
95 ATP
25
Learning Check
The total ATP produced from the -oxidation of
stearic acid (C18) is
1) 108 ATP
2) 146 ATP
3) 148 ATP
26
Solution
The total ATP produced from the -oxidation of
stearic acid (C18) is:
2) 146 ATP
Activation
9 Acetyl CoA
8 NADH
8 FADH2
x 12 ATP
x 3 ATP
x 2 ATP
-2 ATP
108 ATP
24 ATP
16 ATP
146 ATP
27
Chapter 24 Metabolic Pathways for
Lipids and Amino Acids
24.4
Ketogenesis and Ketone Bodies
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Ketogenesis
In ketogenesis
 Large amounts of acetyl CoA accumulate.
 Two acetyl CoA molecules combine to form
acetoacetyl CoA.
 Acetoacetyl CoA hydrolyzes to acetoacetate, a
ketone body.
 Acetoacetate reduces to -hydroxybutyrate or
loses CO2 to form acetone, both ketone bodies.
30
Reactions of Ketogenesis
Ketone bodies
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Ketosis
Ketosis occurs
 In diabetes, diets high
in fat, and starvation.
 As ketone bodies
accumulate.
 When acidic ketone
bodies lowers blood
pH below 7.4
(acidosis).
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Ketone Bodies and Diabetes
In diabetes
 Insulin does not
function property.
 Glucose levels are
insufficient for energy
needs.
 Fats are broken
down to acetyl CoA.
 Ketogenesis
produces ketone
bodies.
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Learning Check
In ketogenesis, match the type of reaction with
1) oxidation 2) reduction 3) decarboxylation
A. acetoacetate produces acetone
B. acetoacetate produces β-hydroxybutyrate
34
Solution
In ketogenesis, match the type of reaction with
1) oxidation 2) reduction 3) decarboxylation
A. acetoacetate produces acetone
3
B. acetoacetate produces β-hydroxybutyrate 2
35
Chapter 24 Metabolic Pathways for
Lipids and Amino Acids
24.5
Fatty Acid Synthesis
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36
Lipogenesis: Fatty Acid Synthesis
Lipogenesis
 Is the synthesis of fatty acids from acetyl CoA.
 Occurs in the cytosol.
 Uses reduced coenzyme NADPH (NADH with a
phosphate group).
 Requires an acyl carrier protein (ACP).
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Synthesis of Malonyl CoA
For fatty acid synthesis,
 Acetyl CoA combines with bicarbonate to form
malonyl CoA.
 ATP hydrolysis provides energy.
O
acetyl CoA
||
carboxylase
CH3—C—S—CoA + HCO3- + ATP
acetyl CoA
O
O
||
||
-O—C—CH —C—S—CoA + ADP + P + H+
2
i
malonyl CoA
38
Acetyl and Malonyl Acyl
Carrier Proteins (ACP)
Active forms of acetyl ACP and malonyl-ACP are
produced by combining with acyl carrier proteins (ACP).
O
║
CH3—C—S—CoA + HS-ACP
O
║
CH3—C—S—ACP + HS-CoA
acetyl-ACP
O
O
||
||
-O—C—CH —C—S—CoA + HS-ACP
2
O
O
||
||
-O—C—CH —C—S—ACP + HS-CoA
2
malonyl-ACP
39
Fatty Acid Synthesis: Condensation
and Reduction
In reactions 1 and 2 of fatty
acid synthesis
 Condensation (1) by a
synthase combines
acetyl-ACP with malonylACP to form acetoacetylACP (4C) and CO2.
 Reduction(2) converts a
ketone to an alcohol using
NADPH.
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Fatty Acid Synthesis: Dehydration
and Reduction
In reactions 3 and 4 of
fatty acid synthesis
 Dehydration(3) forms a
trans double bond.
 Reduction (4) converts
the double bond to a
single bond using
NADPH.
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Fatty Acid Synthesis (Lipogenesis)
Cycle Repeats
Fatty acid synthesis
continues as
 Malonyl-ACP
combines with the
four-carbon butyrylACP to form a sixcarbon-ACP.
 The carbon chain
lengthens by two
carbons each cycle.
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Fatty Acid Synthesis (Lipogenesis)
Cycle Completed
Fatty acid synthesis
 Is completed
when palmitoyl
ACP reacts with
water to give
palmitate (C16)
and free ACP.
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Summary of Lipogenesis
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Fatty Acid Length
In fatty acid synthesis
 Shorter fatty acids undergo fewer cycles.
 Longer fatty acids are produced from palmitate using
special enzymes.
 Unsaturated cis bonds are incorporated into a 10carbon fatty acid that is elongated further.
45
Regulation of Fatty Acid Synthesis
In fatty acid synthesis
 A high level of blood glucose and insulin stimulates
glycolysis and pyruvate oxidation.
 More acetyl CoA is available to form fatty acids.
46
Comparing -Oxidation and Fatty
Acid Synthesis
TABLE 24.1
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Learning Check
Match each with the description below:
1) mitochondria
2) cytosol
3) glucagon
4) insulin
5) acetyl ACP
6) malonyl ACP
A.
B.
C.
D.
E.
F.
Site of fatty acid synthesis.
Site of -oxidation.
Starting material for lipogenesis.
Compound added to elongate acyl-ACP.
Activates -oxidation.
Activates lipogenesis.
48
Solution
Match each with the description below:
1) mitochondria
2) cytosol
3) glucagon
4) insulin
5) acetyl ACP
6) malonyl ACP
A. 2 Site of fatty acid synthesis.
B. 1 Site of -oxidation.
C. 5,6 Starting material for lipogenesis.
D. 6 Compound added to elongate acyl-ACP.
E. 3 Activates -oxidation.
F. 4 Activates lipogenesis.
49
Chapter 24 Metabolic Pathways for
Lipids and Amino Acids
24.6
Digestion of Proteins
24.7
Degradation of Amino Acids
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Digestion of Proteins
The digestion of proteins (stage 1)
 Begins in the stomach where HCl in stomach acid
activates pepsin to hydrolyze peptide bonds.
 Continues in the small intestine where trypsin and
chymotrypsin hydrolyze peptides to amino acids.
 Is complete as amino acids enter the bloodstream
for transport to cells.
51
Digestion of Proteins
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Learning Check
Match the end products of digestion with the types of
food:
1. amino acids
2. fatty acids and glycerol
3. glucose
A. fats
B. proteins
C. carbohydrates
53
Solution
Match the end products of digestion with the types of
food:
1. amino acids
2. fatty acids and glycerol
3. glucose
A. fats
B. proteins
C. carbohydrates
2. fatty acids and glycerol
1. amino acids
3. glucose
54
Proteins in the Body
Proteins provide
 Amino acids for
protein synthesis.
 Nitrogen atoms for
nitrogen-containing
compounds.
 Energy when
carbohydrate and
lipid resources are
not available.
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Transamination
In transamination
 Amino acids are degraded in the liver.
 An amino group is transferred from an amino acid
to an -keto acid, usually -ketoglutarate.
 The reaction is catalyzed by a transaminase or
aminotransferase.
 A new amino acid, usually glutamate, and a new
-keto acid are formed.
56
A Transamination Reaction
NH3+
O
alanine
|
||
aminotransferase
CH3—CH—COO- + -OOC—C—CH2—CH2—COOalanine
O
||
CH3—C—COO- +
pyruvate
-ketoglutarate
NH3+
|
-OOC—CH—CH —CH —COO2
2
glutamate
57
Oxidative Deamination
Oxidative deamination
 Removes the amino group as an ammonium ion from
glutamate.
 Provides -ketoglutarate for transamination.
NH3+
glutamate
|
dehydrogenase
-OOC—CH—CH —CH —COO- + NAD+ + H O
2
2
2
glutamate
O
||
-OOC—C—CH —CH —COO- + NH + + NADH
2
2
4
-ketoglutarate
58
Learning Check
Write the products from the transamination of
-ketoglutarate by aspartate.
NH3+
|
-OOC—CH—CH —COO2
aspartate
O
||
-OOC—C—CH —CH —COO2
2
-ketoglutarate
59
Solution
Write the products from the transamination of
-ketoglutarate by aspartate.
O
||
-OOC—C—CH —COO2
oxaloacetate
NH3+
|
-OOC—CH—CH —CH —COO2
2
glutamate
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Chapter 24 Metabolic Pathways
for Lipids and Amino Acids
24.8
Urea Cycle
O
||
H2N—C—NH2
urea
61
Urea Cycle
The urea cycle
 Detoxifies ammonium ion from amino acid
degradation.
 Converts ammonium ion to urea in the liver.
O
||
H2N—C—NH2 urea
 Provides 25-30 g urea daily for urine formation in
the kidneys.
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Carbamoyl Phosphate
Carbamoyl phosphate is formed
 In the mitochondria, when ammonium ion reacts
with CO2 from the citric acid cycle, 2 ATP, and
water.
carbomyl phosphate
synthetase
NH4+ + CO2 + 2ATP + H2O
O
O
||
||
H2N—C—O—P—O- + 2ADP + Pi
|
Ocarbamoyl phosphate
63
Reaction 1 Transfer of
Carbamoyl Group
In reaction 1 of the urea cycle,
 The carbamoyl group is transferred to ornithine to
form citrulline.
 Citrulline moves across the mitochondrial
membrane into the cytosol.
64
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Reaction 2 Condensation with
Aspartate
In reaction 2 of the urea
cycle,
 That takes place in the
cytosol, citrulline
combines with
aspartate.
 Hydrolysis of ATP to
AMP provides energy.
 The N in aspartate is
part of urea.
Cytosol
65
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Reaction 3 Cleavage of Fumarate
In reaction 3 of the urea cycle, fumarate
 Is cleaved from argininosuccinate.
 Enters the citric acid cycle.
66
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Reaction 4 Hydrolysis Forms
Urea
In reaction 4 of the urea
cycle,
 Arginine is hydrolyzed
 Urea forms.
 Ornithine returns to the
mitochondrion to pick
up another carbamoyl
group to repeat the
urea cycle.
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Urea Cycle
68
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Summary of Urea Cycle
The urea cycle converts:
 Ammonium ion to urea
 Aspartate to Fumarate
 3ATP to 2ADP, AMP, 4Pi
NH4+ + CO2 + 3ATP + aspartate + 2H2O
urea + 2ADP + AMP + 4Pi + fumarate
69
Learning Check
Identify the site for each as:
1) mitochondrion
2) cytosol
A.
B.
C.
D.
E.
Formation of urea.
Formation of carbamoyl phosphate.
Aspartate combines with citrulline.
Fumarate is cleaved.
Citrulline forms.
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Solution
Identify the site for each as:
1) mitochondrion
2) cytosol
A. 2
B. 1
C. 2
D. 2
E. 1
Formation of urea.
Formation of carbamoyl phosphate.
Aspartate combines with citrulline.
Fumarate is cleaved.
Citrulline forms.
71
Chapter 24 Metabolic Pathways
for Lipids and Amino Acids
24.9
Fates of the Carbon Atoms from
Amino Acids
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Carbon Atoms from Amino Acids
When needed, carbon skeletons of amino acids are used
to produce energy by forming intermediates of the citric
acid cycle.
 Three-carbon skeletons
alanine, serine, and cysteine
 Four-carbon skeletons
aspartate, asparagine
 Five-carbon skeletons
glutamine, glutamate, proline,
arginine, histidine
pyruvate
oxaloacetate
glutamate
73
Glucogenic and Ketogenic Amino
Acids
Amino acids are classified as
 Glucogenic if they generate pyruvate or
oxaloacete, which can be used to synthesize
glucose.
 Ketogenic if they generate acetoacetyl CoA or
acetyl CoA, which can form ketone bodies or fatty
acids.
74
Amino Acid Pathways to Citric
Acid Intermediates
Ketogenic
Glucogenic
75
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Amino Acid Pathways to Pyruvate
and Oxaloacetate
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Glucogenic Amino Acids that Form
Intermediates of the Citric Acid Cycle
77
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Learning Check
Match each the intermediate with the amino acid that
provides its carbon skeleton.
1) pyruvate 2) fumarate 3) -ketoglutarate
A.
B.
C.
D.
cysteine
glutamine
aspartate
serine
78
Solution
Match each the intermediate with the amino acid that
provides its carbon skeleton.
1) pyruvate 2) fumarate 3) -ketoglutarate
A. 1
B. 3
C. 2
D. 1
cysteine
glutamine
aspartate
serine
79
Learning Check
Identify each as glucogenic (G) or ketogenic (K)
A. alanine
B. lysine
C. phenylalanine
D. aspartate
E. glutamate
80
Solution
Identify each as glucogenic (G) or ketogenic (K)
A. G alanine
B. K lysine
C. K phenylalanine
D. G aspartate
E. G glutamate
81
Chapter 24 Metabolic Pathways
for Lipids and Amino Acids
24.10
Synthesis of Amino Acids
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Sources of Amino Acids
 Essential amino acids must be obtained in the diet.
 Nonessential amino acids are synthesized in the
body.
TABLE 24.3
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83
Synthesis of Amino Acids
 In humans, transamination of compounds from
glycolysis or the citric acid cycle produces
nonessential amino acids.
84
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Synthesis of Glutamine
 Glutamine is synthesized by adding another amino
group to glutamate.
NH3+
|
-OOC—CH—CH —CH —COO- + NH + ATP
2
2
3
glutamine
synthetase
glutamate
NH3+
O
|
||
-OOC—CH—CH —CH —C—NH + ADP + P
2
2
2
i
glutamine
85
Learning Check
Match each amino acid with the intermediate needed for
its synthesis:
1) alanine 2) glutamate 3) aspartate
A. pyruvate
B. oxaloacetate
C. -ketoglutarate
86
Solution
Match each amino acid with the intermediate needed for
its synthesis:
1) alanine 2) glutamate 3) aspartate
A. 1 pyruvate
B. 3 oxaloacetate
C. 2 -ketoglutarate
87
Phenylketonurea (PKU)
In phenylketonurea (PKU)
 The gene that converts phenylalanine to tyrosine is
defective.
 Phenylalanine forms phenylpyruvate
(transamination), which goes to phenylacetate
(decarboxylation).
 High levels of phenylacetate cause severe mental
retardation.
 A diet low in phenylalanine and high in tyrosine is
recommended.
88
Phenylketonurea (PKU)
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89
Overview of Metabolism
In metabolism
 Catabolic pathways degrade large molecules.
 Anabolic pathway synthesize molecules.
 Branch points determine which compounds are
degraded to acetyl CoA to meet energy needs or
converted to glycogen for storage.
 Excess glucose is converted to body fat.
 Fatty acids and amino acids are used for energy
when carbohydrates are not available.
 Some amino acids are produced by transamination.
90
91
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