Upload
adrian-munoz-calderon
View
217
Download
1
Embed Size (px)
Citation preview
7/31/2019 1 Metabolism Metabolic Pathways 160712
1/57
7/31/2019 1 Metabolism Metabolic Pathways 160712
2/57
Metabolism(The Acquisition and Utilization of Free Energy)
Catabolism: exergonic oxidation
Anabolism: endergonic processes
7/31/2019 1 Metabolism Metabolic Pathways 160712
3/57
(Oxidation)
(Biosynthesis)
(Exergonic)
(Endergonic)
7/31/2019 1 Metabolism Metabolic Pathways 160712
4/57
Function of ATP
Cells make use of ATP for:
Chemical workATP supplies energy tosynthesize macromolecules, and therefore theorganism
Transport workATP supplies energy needed to
pump substances across the plasma membrane Mechanical workATP supplies energy for
cellular movements
7/31/2019 1 Metabolism Metabolic Pathways 160712
5/57
Redox Reactions
7/31/2019 1 Metabolism Metabolic Pathways 160712
6/57
The electron transfer reaction:
NAD+ + 2e + H+ NADH.
It may also be written as:
NAD+ + 2e + 2H+ NADH + H+
N
R
H
C
NH2
O
N
R
C
NH2
OH H
+2e
+H
+
NAD+
NADH
NAD (Nicotinamide Adenine Dinucleotide)Electron transfer from NADH providesfree energy
(NAD+/NADH)
7/31/2019 1 Metabolism Metabolic Pathways 160712
7/57
FAD accepts 2e+ 2H+ in going to its reduced state:
FAD + 2e + 2H+
FADH2
C
C
C
H
C
C
H
C
N
C
C
N
N
C
NH
C
H3C
H3C
O
O
CH2
HC
HC
HC
H2C
OH
OPOPO
O
O-
O
O-
Ribose
OH
OH
Adenine
C
C
C
H
C
C
H
C
N
C
C
H
N
N
H
C
NH
C
H3C
H3C
O
O
CH2
HC
HC
HC
H2C
OH
OPOPO
O
O-
O
O-
Ribose
OH
OH
AdenineFA FAD
2e
+2H+
dimethylisoalloxazin
FAD (Flavin Adenine Dinucleotide)
7/31/2019 1 Metabolism Metabolic Pathways 160712
8/57
Metabolic Networks
Reactions:
Pathways:
Networks:
A B
A B C D
A B C E
D
7/31/2019 1 Metabolism Metabolic Pathways 160712
9/57
Metabolic Pathways
A> B
7/31/2019 1 Metabolism Metabolic Pathways 160712
10/57
Metabolic Pathways
A> B > C > D > E
7/31/2019 1 Metabolism Metabolic Pathways 160712
11/57
Metabolic Pathways
A> B > C > D > E
F > G > H
7/31/2019 1 Metabolism Metabolic Pathways 160712
12/57
Metabolic Pathways
A> B > C > D > E
F > G > H
e2e1
e5
e4
e6 e7
e3
7/31/2019 1 Metabolism Metabolic Pathways 160712
13/57
Metabolic Pathways
A> B > C > D > E
F > G > H
e2e1
e5
e4
e6 e7
e3
7/31/2019 1 Metabolism Metabolic Pathways 160712
14/57
Metabolic Pathways
A> B > C > D > E
F > G > H
e2e1
e5
e4
e6 e7
S
PCell membrane
e3
7/31/2019 1 Metabolism Metabolic Pathways 160712
15/57
7/31/2019 1 Metabolism Metabolic Pathways 160712
16/57
7/31/2019 1 Metabolism Metabolic Pathways 160712
17/57
7/31/2019 1 Metabolism Metabolic Pathways 160712
18/57
Properties of Metabolic Pathways
Irreversible (overall): reversibility of individualsteps
Separate Anabolic and Catabolic Pathways First Committed (Exergonic) Step: others
close to equilibrium
Regulation (usually first committed step):
often rate-limiting Compartamentation: transport
7/31/2019 1 Metabolism Metabolic Pathways 160712
19/57
Feedback inhibition
Enzyme modulators
No enzyme
Enzyme isolation Energy availability - ATP
Control of Metabolic Pathways
7/31/2019 1 Metabolism Metabolic Pathways 160712
20/57
Example of Metabolic Regulation
7/31/2019 1 Metabolism Metabolic Pathways 160712
21/57
A Summary of the Pathways of Catabolism and Anabolism
C t b li Th B kd f M t i t
7/31/2019 1 Metabolism Metabolic Pathways 160712
22/57
Catabolism: The Breakdown of Macro-nutrients
7/31/2019 1 Metabolism Metabolic Pathways 160712
23/57
Glycolysis
Phosphorylation
Pyruvate Anaerobic respiration
Lactate production
2 ATPs produced
Energy Production
ATP
Overview of aerobic pathways for ATP Production
7/31/2019 1 Metabolism Metabolic Pathways 160712
24/57
Glycolysis
Event 1 - Phosphorylation
two phosphates
added to glucose
requires ATP
Event 2Splitting (cleavage)
6-carbon glucose split
into two 3-carbon
molecules
4-14
7/31/2019 1 Metabolism Metabolic Pathways 160712
25/57
Glycolysis
Event 3Production of NADH and
ATP
hydrogen atoms are released
hydrogen atoms bind to NAD
+
toproduce NADH
NADH delivers hydrogen atoms
to electron transport chain if
oxygen is available
ADP is phosphorylated tobecome ATP
two molecules of pyruvic acid
are produced
4-15
7/31/2019 1 Metabolism Metabolic Pathways 160712
26/57
Glycolysis Summary
Inputs:
Glucose
2 NAD+ 2 ATP
4 ADP + 2 P
Outputs:
2 pyruvate
2 NADH 4 ADP
2 ATP (net gain)
7/31/2019 1 Metabolism Metabolic Pathways 160712
27/57
7/31/2019 1 Metabolism Metabolic Pathways 160712
28/57
Anaerobic Reactions
If oxygen is not available -
electron transport chaincannot accept NADH
pyruvic acid is converted to
lactic acid
glycolysis is inhibited
ATP production declines
4-16
7/31/2019 1 Metabolism Metabolic Pathways 160712
29/57
Fermentation
In the absence of oxygen, the end-product
of glycolysis, pyruvate, is used in
fermentation.During glycolysis, all the NAD+ becomes
saturated with electrons (NADH). When this
happens, glycolysis will stop.
2 NADH and 2 ATP produced.
Pyruvate is used as the electron acceptor
resetting the NAD+ for use in glycolysis.
7/31/2019 1 Metabolism Metabolic Pathways 160712
30/57
Fermentation2 Types
Animals add extracted
electrons to pyruvate
forming lactate.
Reversible when oxygen
becomes available.
Muscle fatigue
Yeasts, single-celled fungi,
produce ethanol.
Present in wine & beer.
Alcoholic fermentation
7/31/2019 1 Metabolism Metabolic Pathways 160712
31/57
31
Pyruvate
Ethanol
+
lactate
+
acetate
+
succinate
+
carbon dioxide
+ hydrogen
+
formate
Ethanol
+ 2,3-butanediol +
formate
+
lactate
+
carbon dioxide
+
hydrogen
Lacta
te
Ethanol
+
carbon
dioxide
Propiona
te +
carbon dioxide
+ hydrogen +
acetate
Butyrate
+
butanol
+ isopropanol +
acetone
+
carbon dioxide
fermentation
Escherichia Enterobacter Lactobacillus Saccharomyces Propioni-bacterium Clostridium
7/31/2019 1 Metabolism Metabolic Pathways 160712
32/57
Glycolysis takes place in the cytoplasm of almost all cells.
7/31/2019 1 Metabolism Metabolic Pathways 160712
33/57
Aerobic Reactions
If oxygen is available
pyruvic acid is used to produce
acetyl CoA
citric acid cycle begins
electron transport chain functions
carbon dioxide and water are formed
36 molecules of ATP produced perglucose molecule
4-17
Citric Acid Cycle
7/31/2019 1 Metabolism Metabolic Pathways 160712
34/57
Citric Acid Cycle
7/31/2019 1 Metabolism Metabolic Pathways 160712
35/57
Citric acid cycle
7/31/2019 1 Metabolism Metabolic Pathways 160712
36/57
Citric acid cycle inputs and outputs
per glucose molecule
Inputs:
2 acetyl groups
6 NAD+
2 FAD
2 ADP + 2 P
Outputs:
4 CO2
6 NADH
2 FADH2
2 ATP
7/31/2019 1 Metabolism Metabolic Pathways 160712
37/57
Aerobic Respiration
In aerobic respiration, ATP forms as electrons
are harvested, transferred along the electron
transport chain and eventually donated to O2
gas.
Oxygen is required!
Glucose is completely oxidized.
C6H12O6 + 6O2 6CO2 + 6H2O + energy
Glucose Oxygen Carbon Water (heat or ATP)
Dioxide
7/31/2019 1 Metabolism Metabolic Pathways 160712
38/57
7/31/2019 1 Metabolism Metabolic Pathways 160712
39/57
Mitochondria Inner Structure
7/31/2019 1 Metabolism Metabolic Pathways 160712
40/57
Organization of cristae
7/31/2019 1 Metabolism Metabolic Pathways 160712
41/57
Using Electrons to Make ATP
NADH & FADH2 contain
energized electrons.
NADH molecules carry their
electrons to the inner
mitochondrial membrane where
they transfer electrons to a
series of membrane bound
proteinsthe electron
transport chain.
7/31/2019 1 Metabolism Metabolic Pathways 160712
42/57
7/31/2019 1 Metabolism Metabolic Pathways 160712
43/57
Producing ATP- Chemiosmosis
A strong gradient withmany protons outside thematrix and few inside is setup.
Protons are driven back
into the matrix.
They must pass throughspecial channels thatwill drive synthesis of
ATP. Oxidative
phosphorylation
7/31/2019 1 Metabolism Metabolic Pathways 160712
44/57
Energy Yield from Glucose
Metabolism Per glucose molecule, there is a net gain of
two ATP from glycolysis, which occurs in
the cytoplasm by substrate-levelphosphorylation.
The citric acid cycle, occurring in the matrix
of mitochondria, adds six more ATP, also bysubstrate-level phosphorylation.
7/31/2019 1 Metabolism Metabolic Pathways 160712
45/57
Most ATP is produced by the electron transport
system and chemiosmosis.
Per glucose molecule, ten NADH and two FADH2take electrons to the electron transport system;
three ATP are formed per NADH and two ATP per
FADH2
.
Electrons carried by NADH produced during
glycolysis are shuttled to the electron transport
chain by an organic molecule.
Energy Yield from Glucose
Metabolism
7/31/2019 1 Metabolism Metabolic Pathways 160712
46/57
Accounting of energy yield per glucose
molecule breakdown
7/31/2019 1 Metabolism Metabolic Pathways 160712
47/57
Glucose + 2 ATP + 36 ADP + 36 Pi + 6 O2 6CO2 + 2 ADP + 36 ATP + 6 H2O
7/31/2019 1 Metabolism Metabolic Pathways 160712
48/57
7/31/2019 1 Metabolism Metabolic Pathways 160712
49/57
Metabolism of Proteins
Proteins digested in the gut into amino acidswhich are then absorbed into blood andextracellular fluid.
Excess proteins can serve as fuel likecarbohydrates and fats.
Nitrogen is removed producing carbon skeletonsand ammonia.
Carbon skeletons oxidized.
7/31/2019 1 Metabolism Metabolic Pathways 160712
50/57
Metabolism of Proteins
Ammonia is highly
toxic, but soluble.
Can be excreted by
aquatic organismsas ammonia.
Terrestrial organisms
must detoxify it first.
7/31/2019 1 Metabolism Metabolic Pathways 160712
51/57
7/31/2019 1 Metabolism Metabolic Pathways 160712
52/57
7/31/2019 1 Metabolism Metabolic Pathways 160712
53/57
Glycogensynthesis
Liver storage
Glucose toglycogen
Gluconeogenesis
Amino acidsGlycerol
Lactate
Synthetic (Anabolic) pathways
Figure 4-29: Gluconeogenesis
7/31/2019 1 Metabolism Metabolic Pathways 160712
54/57
Lipogenesis
Lipid synthesis
7/31/2019 1 Metabolism Metabolic Pathways 160712
55/57
Lipid Synthesis
7/31/2019 1 Metabolism Metabolic Pathways 160712
56/57
Alfonse, Biochemistry makes my head hurt!!
7/31/2019 1 Metabolism Metabolic Pathways 160712
57/57
\