Chapter 18 Metabolic Pathways
Chapter 18 Metabolic Pathways
Chapter 18 Metabolic Pathways
1
Metabolism
Metabolism involves
all chemical reactions that
provide energy and
substances needed for growth
catabolic reactions that
break down large, complex
molecules to provide energy
and smaller molecules
anabolic reactions that use
ATP energy to build larger
molecules
2
Stages of Metabolism
3
Stages of Metabolism
4
Cell Structure and Metabolism
5
Cell Components and Function
6
ATP and Energy
7
Hydrolysis of ATP
8
ATP and Muscle Contraction
Muscle fibers
contain the protein fibers actin and myosin
contract (slide closer together) when a nerve impulse
increases Ca2+
obtain the energy for contraction from the hydrolysis of
ATP
return to the relaxed position as Ca2+ and ATP decrease
9
ATP and Muscle Contraction
10
Stage 1: Digestion of Carbohydrates
In stage 1,
carbohydrates begin digestion in the mouth
-glycosidic bonds in amylose and amylopectin are
hydrolyzed by enzymes released from salivary glands
smaller polysaccharides such as dextrins, maltose, and glucose
are produced
11
Stage 1: Digestion of Carbohydrates
In stage 1,
digestion continues in the small intestine, where enzymes
hydrolyze dextrins to maltose and glucose
maltose, lactose, and sucrose are hydrolyzed to
monosaccharides, mostly glucose, which enter the bloodstream
for transport to the cells
12
Carbohydrate Digestion
13
Digestion of Fats
14
Digestion of Triacylglycerols
15
Digestion of Proteins
16
Digestion of Proteins
17
Oxidation and Reduction
reduction reactions
require coenzymes that pick up 2 H or loss of oxygen
18
Metabolic Pathways:
Oxidation and Reduction
19
Coenzyme NAD+
20
Structure of Coenzyme NAD+
NAD+
contains ADP, ribose, and
nicotinamide
is reduced to NADH when
NAD+ accepts 2H+ and 2
e
21
NAD+ Participates in Oxidation
22
Coenzyme FAD
Reduction
23
Structure of Coenzyme FAD
24
Structure of Coenzyme FAD
25
Coenzyme A
O O
|| ||
CH3C + HSCoA CH3CSCoA
26
Structure of Coenzyme A
27
Coenzyme A: Synthesis of Acetyl CoA
28
Learning Check
29
Solution
30
Types of Metabolic Reactions
31
Stage 2: Glycolysis
Stage 2: Glycolysis
is a metabolic pathway
that uses glucose, a
digestion product from
carbohydrates
degrades six-carbon
glucose molecules to
three-carbon pyruvate
molecules
is an anaerobic (no
oxygen) process
32
Glycolysis: Energy Investment
In reactions 1 to 5 of glycolysis,
energy is required to add phosphate groups to glucose
glucose is converted to two three-carbon molecules
33
Glycolysis: Energy Investment
Reaction 1 Phosphorylation
A phosphate from ATP is added
to glucose, forming glucose-
6-phosphate and ADP.
Reaction 2 Isomerization
The glucose-6-phosphate, the
aldose from reaction 1,
undergoes isomerization to
fructose-6-phosphate, which
is a ketose.
34
Glycolysis: Energy Investment
Reaction 3 Phosphorylation
Fructose-6-phosphate reacts with
a second ATP, adding a second
phosphate to the molecule:
fructose-1,6-biphosphate.
Reaction 4 Cleavage
Fructose-1,6-bisphosphate is split
into two three-carbon
phosphate isomers:
dihydroxyacetone phosphate
and glyceraldehyde-3-
phosphate.
35
Glycolysis: Energy Investment
Reaction 5 Isomerization
Because dihydroxyacetone
phosphate is a ketone, it
cannot react further. It
undergoes isomerization to
provide a second molecule of
glyceraldehyde-3-phosphate,
which can be oxidized. Now
all six-carbon atoms from
glucose are contained
in two identical triose
phosphates.
36
Glycolysis: Energy Production
In reactions 6 to 10 of glycolysis,
energy is generated as
sugar phosphates are cleaved
to triose phosphates
four ATP molecules are
produced
37
Glycolysis: Energy Production
Reaction 6
Oxidation, Phosphorylation
The aldehyde group of each
glyceraldehyde-3-phosphate is
oxidized to a carboxyl group by
the coenzyme, which is
reduced to NADH and H+. A
phosphate adds to the new
carboxyl groups to form two
molecules of the high-energy
compound 1,3-
bisphosphoglycerate.
38
Glycolysis: Energy Production
Reaction 7 Phosphate
Transfer
Phosphorylation transfers a
phosphate group from each
1,3-bisphosphoglycerate to
ADP, producing 2 molecules
of ATP. At this point 2 ATPs
are produced, balancing the
two ATPs consumed in
reactions 1 and 3.
39
Glycolysis: Energy Production
Reaction 8 Isomerization
Two 3-phosphoglycerate
molecules isomerize, moving
the phosphate group from
carbon 3 to carbon 2 and
yielding two 2-
phosphoglycerates.
Reaction 9 Dehydration
Each phosphoglycerate undergoes
dehydration to give two high-
energy molecules of
phosphoenolpyruvate.
40
Glycolysis: Energy Production
Reaction 10 Phosphate
Transfer
In a second direct phosphate
transfer, phosphate groups
from two
phosphoenolpyruvate are
transferred to 2 ADPs, forming
2 pyruvates and 2 ATPs.
41
Glycolysis: Overall Reaction
In glycolysis,
two ATP add phosphate to glucose- and fructose-6-phosphate
four ATP form as phosphate groups add to ADP
there is a net gain of 2 ATP and 2 NADH
42
Learning Check
43
Solution
44
Pyruvate: Aerobic Conditions
O O Pyruvate
|| || dehydrogenase
CH3CCO + HSCoA + NAD+
Pyruvate
O
||
CH3CSCoA + CO2 + NADH
Acetyl CoA
45
Pyruvate: Anaerobic Conditions
O O Lactate
|| || dehydrogenase
CH3CCO + NADH + H+
Pyruvate
OH O
| ||
CH3CHCO + NAD+
Lactate
46
Pyruvate Pathways, Aerobic and Anaerobic
47
Lactate in Muscles
48
Oxidation and Reduction
reduction reactions
require coenzymes that pick up 2 H or loss of oxygen
49
Metabolic Pathways:
Oxidation and Reduction
50
Coenzyme NAD+
51
Structure of Coenzyme NAD+
NAD+
contains ADP, ribose, and
nicotinamide
is reduced to NADH when
NAD+ accepts 2H+ and 2
e
52
NAD+ Participates in Oxidation
53
Coenzyme FAD
Reduction
54
Structure of Coenzyme FAD
55
Structure of Coenzyme FAD
56
Coenzyme A
O O
|| ||
CH3C + HSCoA CH3CSCoA
57
Structure of Coenzyme A
58
Coenzyme A: Synthesis of Acetyl CoA
59
Learning Check
60
Solution
61
Types of Metabolic Reactions
62
Citric Acid Cycle
63
Citric Acid Cycle Overview
64
Citric Acid Cycle
65
Reaction 1: Formation of Citrate
66
Reaction 2: Isomerization to Isocitrate
Citrate
isomerizes to isocitrate
converts the tertiary OH group in citrate to a secondary
OH in isocitrate that can be oxidized
COO COO
C H2 C H2
HO C COO H C COO
C H2 HO C H
COO COO
Citrate Isocitrate
67
Summary of Reactions 1 and 2
68
Reaction 3: 1st Oxidative Decarboxylation
Isocitrate -Ketoglutarate
69
Reaction 4: 2nd Oxidative Decarboxylation
-Ketoglutarate
undergoes decarboxylation to form succinyl CoA
produces a four-carbon compound that bonds to CoA
provides H+ and 2 e to form NADH
COO COO
C H2 C H2
C H2 NAD+ C H2 + CO2 + NADH
C O CoA-SH C O
COO S CoA
-Ketoglutarate Succinyl CoA
70
Summary of Reactions 3 and 4
71
Reaction 5: Hydrolysis
COO-
COO-
CH2
CH2
CH2 + GDP + Pi + CoA + GTP
CH2
C O
COO-
S CoA
Succinyl CoA Succinate
72
Reaction 6: Dehydrogenation
73
Summary of Reactions 5 and 6
74
Reaction 7: Hydration of Fumarate
COO
COO
C H HO C H
+ H2 O
H C H C H
COO COO
Fumarate Malate
75
Reaction 8: Dehydrogenation
H C H C H2
COO COO
Malate Oxaloacetate
76
Summary of Reactions 7 and 8
77
Summary of the Citric Acid Cycle
78
Overall Chemical Reaction for the Citric Acid
Cycle
79
Stage 3 Electron Transport
In electron transport,
electron carriers are used
hydrogen ions and electrons from NADH and FADH2 are
passed from one electron carrier to the next and then
combine with oxygen to make H2O
are oxidized and reduced to provide energy for the
synthesis of ATP from ADP and Pi
80
Electron Carriers
81
Electron Transport Chain
82
Enzyme Complex I
83
Enzyme Complex II
84
Enzyme Complex III
85
Enzyme Complex IV
4 e + 4H+ + Q2 2H2O
86
Oxidative Phosphorylation
87
Oxidative Phosphorylation
ATP synthase
ADP + Pi + Energy ATP
88
ATP Synthesis
89
ATP from Glycolysis
90
ATP from Glycolysis
91
ATP from Oxidation of Two Pyruvates
92
ATP from the Citric Acid Cycle
Because each glucose provides two acetyl CoA, two turns of the
citric acid cycle produce 24 ATPs.
2 Acetyl CoA 4CO2 + 24ATP (two turns of citric acid cycle)
93
ATP from the Complete Oxidation of Glucose
94
The Complete Oxidation of Glucose
95
Learning Check
96
Solution
97
Learning Check
98
Solution
99
b Oxidation of Fatty Acids
100
Fatty Acid Activation
101
Reactions 1 and 2 of b-Oxidation Cycle
Reaction 1 Dehydrogenation
Hydrogen atoms removed by FAD from the and carbons
form a double bond and FADH2.
Reaction 2 Hydration
HOH adds across the double bond, the OH on the
carbon.
102
Reactions 1 and 2 of b-Oxidation Cycle
103
Reaction 3 of b-Oxidation Cycle
Reaction 3 Oxidation
The OH on the carbon is oxidized by NAD+, forming a
ketone and NADH + H+.
104
Reaction 4 of b-Oxidation Cycle
Reaction 4 Cleavage
The CC is cleaved to yield acetyl CoA and a shorter
(8C) fatty acyl CoA. The process is repeated until the
fatty acid is completely broken down.
105
Reaction 4 of b-Oxidation Cycle
106
Learning Check
A. Water is added.
B. FADH2 forms.
C. A two-carbon unit is removed.
D. A hydroxyl group is oxidized.
E. NADH forms.
107
Solution
108
Cycles of b Oxidation
109
ATP from Fatty Acid Oxidation
110
ATP from Oxidation of Myristic Acid
Source ATPs
Activation 2 ATP
7 acetyl CoA
(14 C atoms x 1 acetyl CoA/2 C atoms)
7 acetyl CoA x 12 ATPs/acetyl CoA 84 ATP
6 -oxidation cycles (coenzymes)
6 FADH2 x 2 ATP/FADH2 12 ATP
6 NADH x 3 ATP/NADH 18 ATP
Total 112 ATP
111
Learning Check
112
Solution
113
Oxidation of Unsaturated Fatty Acids
114
Ketone Bodies
If carbohydrates
are not available,
body fat breaks
down to meet
energy needs
compounds called
ketone bodies form
115
Formation of Ketone Bodies
116
Ketosis
Ketosis occurs
in diabetes, diets high in
fat, and starvation
as ketone bodies
accumulate
when acidic ketone
bodies lower blood pH
below 7.4 (acidosis)
117
Fatty Acid Synthesis from Carbohydrates
When the body has met all its energy needs and the glycogen
stores are full, excess acetyl CoA from the breakdown of
carbohydrates is used to form new fatty acids.
In this process,
two-carbon acetyl units are linked to give new fatty acids
undergo synthesis reactions that are the reverse of the -
oxidation reactions
the synthesis occurs in the cytosol instead of the mitochondria
118
Fatty Acid Synthesis from Carbohydrates
In diabetes,
insulin does not function properly
glucose levels are insufficient for
energy needs
fats are broken down to acetyl CoA
ketone bodies form
119
Degradation of Amino Acids
Proteins provide
120
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
a new amino acid and -keto acid are formed
when alanine combines with -ketoglutarate, pyruvate and
glutamate are produced
121
A Transamination Reaction
Alanine
NH3+ O transaminase
| ||
CH3CHCOO + OOCCCH CH COO
2 2
Alanine -Ketoglutarate
O NH3+
|| |
CH3CCOO + OOCCHCH CH COO
2 2
Pyruvate Glutamate
(new -ketoacid) (new amino acid)
122
Oxidative Deamination
Oxidative deamination
removes the ammonium group (NH3+) from glutamate as
NH4+
regenerates -ketoglutarate for transamination
NH3+ Glutamate
dehydrogenase
OOCCHCH CH COO + NAD+ + H O
2 2 2
Glutamate
O
||
OOCCCH CH COO + NH + + NADH
2 2 4
-Ketoglutarate
123
Learning Check
NH3+
|
OOCCHCH COO
2
Aspartate
+ O
||
OOCCCH CH COO
2 2
-Ketoglutarate
124
Solution
125
Urea Cycle
126
ATP Energy from Amino Acids
Carbon skeletons of amino acids
form intermediates of the citric acid cycle
produce energy
enter the citric acid cycle at different places depending on the
amino acid
Three-carbon skeletons:
alanine, serine, and cysteine pyruvate
Four-carbon skeletons:
aspartate, asparagine oxaloacetate
Five-carbon skeletons:
glutamine, glutamate, proline,
arginine, histidine glutamate
127
Intermediates of the Citric Acid Cycle from
Amino Acids
128
Learning Check
A. cysteine
B. glutamine
C. aspartate
D. serine
129
Solution
A. cysteine pyruvate
B. glutamine -ketoglutarate
C. aspartate fumarate
D. serine pyruvate
130
Overview of Metabolism
In metabolism,
catabolic pathways degrade large molecules
anabolic pathways 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
131
Overview of Metabolism
132
Metabolic Pathways Concept Map
133