Chapter 23 Metabolism and Energy production
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Transcript of Chapter 23 Metabolism and Energy production
Chapter 23
Metabolism and Energy production
Chemistry 203
Metabolism
Chemical reactions in cells that break down or build molecules. It produces energy and provide substances to cell growth.
Catabolic reactions:
Anabolic reactions:
Complex molecules Simple molecules + Energy
Simple molecules + Energy (in cell) Complex molecules
The sum of all the chemical reactions that take place in an organism.
Metabolic Pathway
A series of consecutive reactions.
A linear pathway is the series of reactions that generates a final product different from any of the reactants.
A cyclic pathway is the series of reactions that regenerates the first reactant.
Metabolism in cell
CarbohydratesPolysaccharides
Proteins
Lipids
GlucoseFructose
Galactose
Amino acids
Glycerol
Fatty acids
Stage 1: Digestion and hydrolysis
Glucose Pyruvate Acetyl CoACitricAcidcycle
CO2 & H2O
UreaNH4
+
Stage 2: Degradationand some oxidation
Stage 3: Oxidation to CO2,H2O and energy
e
e
Mitochondria
(Formation of Acetyl CoA)
Cell Structure
Membrane
Nucleus
Cytoplasm
(Cytosol)
Mitochondria
Nucleus: consists the genes that control DNA replication and protein synthesis of the cell.
Cytoplasm: consists all the materials between nucleus and cell membrane.
Cytosol: fluid part of the cytoplasm (electrolytes and enzymes).
Organelles: the specialized structures within cells (carry out specific functions).
Mitochondria: energy producing factories.
Cell Structure
Enzymes in matrix catalyze the oxidation of carbohydrates, fats , and amino acids.
Produce CO2, H2O, and energy.
ATP and Energy
- Adenosine triphosphate (ATP) is produced from the oxidation of food.
- Has a high energy.
- Can be hydrolyzed and produce energy.
ATP and Energy
-O-P-O-P-O-AMPO
O--O
OH2O
ATP ADP
-O-P-O-AMP-O
OH2PO4
-+ + + 7.3 kcal/mol
Pi
(adenosine triphosphate) (adenosine diphosphate) (inorganic phosphate)
- We use this energy for muscle contraction, synthesis an enzyme, send nerve signal, and transport of substances across the cell membrane.
- 1-2 million ATP molecules may be hydrolysis in one second (1 gram in our cells).
- When we eat food, catabolic reactions provide energy to recreate ATP.
ADP + Pi + 7.3 kcal/mol ATP
Phosphorylation is the reverse reaction, where a phosphate group is added to ADP.
Coupled Reactions
Coupled reactions are pairs of reactions that occur together.
The energy released by one reaction is absorbed by the other reaction.
ATP + H2O ∆H = −7.3 kcal/mol
energy is released
ADP + HPO42- ∆H = +7.3 kcal/mol
energy is absorbed
ADP + HPO42−
ATP + H2O
Exothermic: a favorable reaction
Endothermic: an unfavorable reaction
Coupled Reactions
The hydrolysis of ATP provides the energy for the phosphorylation of glucose.
Coupling an energetically unfavorable reaction with a favorable one that releases more energy than the amount required is common in biological reactions.
Stage 1: Digestion
Carbohydrates Lipids (fat) Proteins
Convert large molecules to smaller ones
that can be absorbed by the body.
Digestion: Carbohydrates
+
+
Polysaccharides
Dextrins
Maltose Glucose
Mouth
Salivaryamylase
Stomach pH = 2 (acidic)
Maltose +Maltase
Glucose Glucose
Lactose +Lactase
Galactose Glucose
Sucrose +Sucrase
Fructose Glucose
Small intestinepH = 8
Dextrins
Bloodstream Liver (convert all to glucose)
α-amylase (pancreas)
Digestion: Lipids (fat)
Intestinal wall
Monoacylglycerols + 2 Fatty acids → Triacylglycerols
Small intestine
Bloodstream
Glycerol + 3 Fatty acids
H2C
HC
H2C
Fatty acid
Fatty acid
Fatty acid
+ 2H2O
H2C
HC
H2C
OH
Fatty acid
OH
+ 2 Fatty acids
lipase(pancreas)
Triacylglycerol Monoacylglycerol
Protein
Lipoproteins
Chylomicrons
Lymphatic system
Cells Enzymes hydrolyzes
liver Glucose
Digestion: Proteins
Intestinal wall
Small intestine
Bloodstream
Cells
Stomach
Pepsinogen Pepsin
Proteins Polypeptides
HCl
Polypeptides Amino acids
TypsinChymotrypsin
denaturation + hydrolysis
hydrolysis
Some important coenzymes
2 H atoms 2H+ + 2e-
oxidation Coenzyme + Substrate Coenzyme(+2H) + Substrate(-2H)
Reduced Oxidized
NAD+
FAD
Coenzyme A
Coenzymes
NAD+
Nicotinamide adenine dinucleotide
HH
H
O
HO OH
N
CNH2
-O-P-O-CH2
O
O
AMP H
O
a -N-glycosidic bond
+
The plus sign on NAD+
represents the positivecharge on this nitrogen
Nicotinamide;derivedfrom niacin
ADP
(vitamin)
Ribose
(Vitamin B3)
fish, nuts
- Is an oxidizing agent.
- Participates in reactions that produce (C=O) such as oxidation of alcohols to aldehydes and ketones.
NAD+
CH3-CH2-OH + NAD+ CH3-C-H + NADH + H+
NAD+ + 2H+ + 2e- NADH + H+
NAd
CNH2
OH
H+ 2e-
NAd
CNH2
OH H
+ +
NAD+
(oxidized form)NADH
(reduced form)
:+
O
Reduced
FAD
Flavin adenine dinucleotide
O=P-O-AMP
O-
CH2
C
O
C
C
CH2
N
H OH
OHH
H
N
N
NH3C
H3C O
HO
OH Ribitol
Flavin
Riboflavin
ADP
(Vitamin B2)
(sugar alcohol)Soybeans, almonds, liver
FAD
- Is an oxidizing agent.
- Participates in reaction that produce (C=C) such as dehydrogenation of alkanes.
R-C-C-R + FAD R-C=C-H + FADH2
H H
H H H H
AdN
N
N
NHH3C
H3C O
O
+ 2H+ + 2e-H3C
H3C O
OH
HAdN
N
N
NH
FAD FADH2
Reduced
Coenzyme A (CoA)
Aminoethanethiol
( vitamin B5)
Coenzyme A
whole grain, egg
Coenzyme A (CoA)
CH3-C- + HS-CoA CH3-C-S-CoA
O O
Acetyl group Coenzyme A Acetyl CoA
- It activates acyl groups (RC-), particularly the Acetyl group (CH3C-).
When the thioester bond is broken, 7.5 kcal/mol of energy is released.
R-C-S-R’
O
A Thioester
O O
Metabolism in cell
CarbohydratesPolysaccharides
Proteins
Lipids
GlucoseFructose
Galactose
Amino acids
Glycerol
Fatty acids
Stage 1: Digestion and hydrolysis
Glucose Pyruvate Acetyl CoACitricAcidcycle
CO2 & H2O
UreaNH4
+
Stage 2: Degradationand some oxidation
Stage 3: Oxidation to CO2,H2O and energy
e
e
Mitochondria
(Formation of Acetyl CoA)
- We obtain most of our energy from glucose.
- Glucose is produced when we digest the carbohydrates in our food.
- We do not need oxygen in glycolysis (anaerobic process).
C6H12O6 + 2 NAD+ 2CH3-C-COO- + 2 NADH + 4H+
O
PyruvateGlucose
2 ADP + 2Pi 2 ATP
Glycolysis: Oxidation of glucose
Stage 2: Formation of Acetyl CoA
Inside of cell (Cytoplasm)
Pathways for pyruvate
Aerobic conditions: if we have enough oxygen.
Anaerobic conditions: if we do not have enough oxygen.
- Pyruvate can produce more energy.
Aerobic conditions
- Pyruvate is oxidized and a C atom remove (CO2).
- Acetyl is attached to coenzyme A (CoA).
- Coenzyme NAD+ is required for oxidation.
CH3-C-C-O- + HS-CoA + NAD+ CH3-C-S-CoA + CO2 + NADH
O O
pyruvate Coenzyme A Acetyl CoA
O
Important intermediate productin metabolism.
Anaerobic conditions
- When we exercise, the O2 stored in our muscle cells is used.
- Pyruvate is reduced to lactate.
- Accumulation of lactate causes the muscles to tire and sore.
- Then we breathe rapidly to repay the O2.
- Most lactate is transported to liver to convert back into pyruvate.
CH3-C-C-O- CH3-C-C-O-
O O
pyruvate Lactate
O HO
H
Reduced
NADH + H+ NAD+
Glycogen
- If we get excess glucose (from our diet), glucose convert to glycogen.
- It is stored in muscle and liver.
- We can use it later to convert into glucose and then energy.
- When glycogen stores are full, glucose is converted to triacylglycerols and stored as body fat.
Metabolism in cell
CarbohydratesPolysaccharides
Proteins
Lipids
GlucoseFructose
Galactose
Amino acids
Glycerol
Fatty acids
Stage 1: Digestion and hydrolysis
Glucose Pyruvate Acetyl CoACitricAcidcycle
CO2 & H2O
UreaNH4
+
Stage 2: Degradationand some oxidation
Stage 3: Oxidation to CO2,H2O and energy
e
e
Mitochondria
(Formation of Acetyl CoA)
Stage 3: Citric Acid Cycle (Kerbs Cycle)
- Is a central pathway in metabolism.
- Uses acetyl CoA from the degradation of carbohydrates, lipids, and proteins.
- Two CO2 are given off.
- There are four oxidation steps in the cycle provide H+ and electrons to reduce FAD and NAD+ (FADH2 and NADH).
8 reactions
Reaction 1
Formation of Citrate
CH3-C-S-CoA
O
Acetyl CoA
COO-
C=O
CH2
COO-
Oxaloacetate
COO-
CH2
CH2
COO-
CHO COO-
Citrate
+ CoA-SH
Coenzyme A
+
H2O
CitrateSynthase
Reaction 2
Isomerisation to Isocitrate
COO-
CH2
CH2
COO-
CHO COO-
Citrate Isocitrate
COO-
CH2
C
COO-
CH COO-
HO H
Isomerization
- Because the tertiary –OH cannot be oxidized. (convert to secondary –OH)
Aconitase
Reaction 3
First oxidative decarboxylation (CO2)
Isocitrate
COO-
CH2
C
COO-
CH COO-
HO H
- Oxidation (-OH converts to C=O).- NAD+ is reduced to NADH.- A carboxylate group (-COO-) is removed (CO2).
C-COO-H
CH-COO-
CH2-COO-
HOIsocitrate
C-COO-H
C-COO-
CH2-COO-
C-HH
C-COO-
CH2-COO-
NADH + H+NAD+
-Ketoglutarate
CO2
isocitratedehydrogenase
O O
Oxalosuccinate
COO-
CH2
C
COO-
CH COO-
O
α-Ketoglutrate
COO-
CH2
C
COO-
CH2
O+ CO2
Isocitratedehydrogenase
H+
Reaction 4
Second oxidative decarboxylation (CO2)
α-Ketoglutrate
COO-
CH2
C
COO-
CH2
O CH2
C-COO-
CH2-COO-
-Ketoglutarate
O
CoA-SH
NADHNAD+
-ketoglutaratedehydrogenase
complex
CH2
C
CH2-COO-
SCoAOSuccinyl-CoA
+ CO2
Succinyl CoA
COO-
CH2
C
S-CoA
CH2
O + CO2
- Coenzyme A convert to succinyl CoA.- NAD+ is reduced to NADH.- A second carboxylate group (-COO-) is removed (CO2).
α-Ketoglutratedehydrogenase
(a Thioester)
Reaction 5
Hydrolysis of Succinyl CoA
Succinyl CoA
COO-
CH2
C
S-CoA
CH2
O
- Energy from hydrolysis of succinyl CoA is used to add a phosphate group (Pi) to GDP (guanosine diphosphate).
- The hydrolysis of GTP is used to add a Pi to ADP to produce ATP.
+ H2O + GDP + Pi
COO-
CH2
CH2
COO-
Succinate
+ GTP + CoA-SH
GTP + ADP → GDP+ ATP
Reaction 6
Dehydrogenation of Succinate
- H is removed from two carbon atoms.- Double bond is produced.- FAD is reduced to FADH2.
COO-
CH2
CH2
COO-
Succinate
FAD FADH2
CH2-COO-
CH2-COO-
Succinate
succinatedehydrogenase
C
CH
H
COO-
-OOC
Fumarate
COO-
CH
CH
COO-
Fumarate
Succinatedehydrogenase
Reaction 7
Hydration
- Water adds to double bond of fumarate to produce malate.
COO-
C
CH2
COO-
HO H
Malate
H2O
COO-
CH
CH
COO-
Fumarate
Reaction 8
Dehydrogenation forms oxaloacetate
- -OH group in malate is oxidized to oxaloacetate.
- Coenzyme NAD+ is reduced to NADH + H+.
COO-
C
CH2
COO-
HO H
Malate
COO-
C=O
CH2
COO-
Oxaloacetate
C-COO-
CH2-COO-
Oxaloacetate
NAD+ NADH
malatedehydrogenase
CH-COO-HO
CH2-COO-
L-Malate
O+ H+
The product of step [8] is the starting material for step [1].
Summary
The catabolism of proteins, carbohydrates, and fatty acids
all feed into the citric acid cycle at one or more points:
Citric AcidCycle
Summary
Summary
The main function of the citric acid cycle is to produce reduced coenzymes (NADH and FADH2).
Summary
These molecules enter the electron transport chain (Stage 4) and ultimately produce ATP.
Feedback Mechanism
The rate of the citric acid cycle depends on the body’s need for energy.
When energy demands are high and ATP is low → the cycle is activated.
When energy demands are low and NADH is high → the cycle is inhibited.
Stage 4: Electron Transport & Oxidative Phosphorylation
- Most of energy generated during this stage.
- It is an aerobic respiration (O2 is required).
1. Electron Transport Chain (Respiratory Chain)
2. Oxidative Phosphorylation
Stage 4: Electron Transport Chain
H+ and electrons from NADH and FADH2 are carried by an electron carrieruntil they combine with oxygen to form H2O.
FMN (Flavin Mononucleotide)
Fe-S clusters
Coenzyme Q (CoQ)
Cytochrome (cyt)
Electron carriers
FMN (Flavin Mononucleotide)
O=P-O-AMP
O-
CH2
C
O
C
C
CH2
N
H OH
OHH
H
N
N
NH3C
H3C O
HO
OH Ribitol
Flavin
Riboflavin
(Vitamin B2)
(sugar alcohol)
-
2H+ + 2e-
O=P-O-AMP
O-
CH2
C
O
C
C
CH2
N
H OH
OHH
H
N
N
NH3C
H3C O
HO
OH Ribitol
Flavin
Riboflavin
-
H
H
FMN + 2H+ + 2e- → FMNH2
Reduced
Fe-S Clusters
Fe3+
SS
SS
Cys
Cys
Cys
Cys
Fe2+
SS
SS
Cys
Cys
Cys
Cys
+ 1 e-
Fe3+ + 1e- Fe2+
Reduced
Coenzyme Q (CoQ)
OH
OH
2H+ + 2e-
Reduced Coenzyme Q (QH2)Coenzyme Q
Q + 2H+ + 2e- → QH2
Reduced
Cytochromes (cyt)
- They contain an iron ion (Fe3+) in a heme group.
- They accept an electron and reduce to (Fe2+).
- They pass the electron to the next cytochrome and they are oxidized back to Fe3+.
Fe3+ + 1e- Fe2+
ReducedOxidized
cyt b, cyt c1, cyt c, cyt a, cyt a3
Electron Transport Chain
Mitochondria
4 enzyme complexes (I, II, III and IV)
Complex I
NADH + H+ + FMN → NAD+ + FMNH2
FMNH2 + Q → QH2 + FMN
NADH + H+ + Q → QH2 + NAD+
Complex II
FADH2 + Q → FAD + QH2
Electron Transport Chain
Oxidized
Oxidized
Complex III
QH2 + 2 cyt b (Fe3+) → Q + 2 cyt b (Fe2+) + 2H+
Complex IV
4H+ + 4e- + O2 → 2H2O
Electron Transport Chain
Aerobic
From the electrontransport chain
From inhaled airFrom reduced coenzymes
or the matrix
Chemiosmotic model
- H+ make inner mitochondria acidic.- Produces different proton gradient. - H+ pass through ATP synthase (a protein complex).
ATP synthase
Stage 4: Oxidative Phosphorylation
Transport of electrons produce energy to convert ADP to ATP.
ADP + HPO42- + Energy → ATP + H2O
Energy released from oxidation of The reduced coenzymes fuels phosphorylation
Total ATP
Each NADH entering the electron transport chain produces enough energy to make 2.5 ATPs.
Each FADH2 entering the electron transport chain produces enough energy to make 1.5 ATPs.
The citric acid cycle produces overall:
3 NADH x 2.5 ATP = 7.5 ATP
1 FADH2 x 1.5 ATP = 1.5 ATP
1 GTP = 1 ATP
10 ATP From each Acetyl CoA
(Reaction 5)
Total ATP
Glycolysis: 7 ATP
Oxidation of Pyruvate: 5 ATP
Citric acid cycle: 20 ATP
32 ATPOxidation of glucose
C6H12O6 + 6O2 + 32 ADP + 32 Pi → 6CO2 + 6H2O + 32 ATP
Metabolism in cell
CarbohydratesPolysaccharides
Proteins
Lipids
GlucoseFructose
Galactose
Amino acids
Glycerol
Fatty acids
Stage 1: Digestion and hydrolysis
Glucose Pyruvate Acetyl CoACitricAcidcycle
CO2 & H2O
UreaNH4
+
Stage 2: Degradationand some oxidation
Stage 3: Oxidation to CO2,H2O and energy
e
e
Mitochondria
(Formation of Acetyl CoA)
Oxidation of fatty acids
CH3-(CH2)14-CH2-CH2-C-OH
O α
oxidation
- Oxidation happens in step 2 and 3.
- Each beta oxidation produces acetyl CoA and a shorter fatty acid.
- Oxidation continues until fatty acid is completely break down to acytel CoA.
Oxidation of fatty acids
Fatty acid activation
- Before oxidation, they activate in cytosol.
R-CH2-C-OH
O
+ ATP + HS-CoA R-CH2-C-S-CoA
O
+ H2O + AMP + 2Pi
Fatty acyl CoAFatty acid
-Oxidation: 4 reactions
Reaction 1: Oxidation (dehydrogenation)
R-CH2-C-C-C-S-CoA
O
Fatty acyl CoA
H H
H H
+ FAD R-CH2-C=C-C-S-CoA + FADH2
OH
H
Reaction 2: Hydration
R-CH2-C=C-C-S-CoA + H2O
OH
H
R-CH2-C-C-C-S-CoA
O
H H
HHO
Reaction 3: Oxidation (dehydrogenation)
Reaction 4: Cleavage of Acetyl CoA
R-CH2-C-C-C-S-CoA + NAD+
O
H H
HHO
R-CH2-C-CH2-C-S-CoA + NADH+ H+
OO
R-CH2-C-CH2-C-S-CoA + CoA-SH
OO
R-CH2-C-S-CoA
O
CH3-C-S-CoA
O
+
Acetyl CoAFatty acyl CoA
Oxidation of fatty acids
One cycle of -oxidation
R-CH2-CH2-C-S-CoA + NAD+ + FAD + H2O + CoA-SH
O
R-C-S-CoA
O
CH3-C-S-CoA + NADH + H+ + FADH2
O
+
Acetyl CoAFatty acyl CoA
# of Acetyl CoA =# of fatty acid carbon
2= 1 + oxidation cycles
Ketone bodies
- If carbohydrates are not available to produce energy.
- Body breaks down body fat to fatty acids and then Acetyl CoA.
- Acetyl CoA combine together to produce ketone bodies.
- They are produced in liver.
- They are transported to cells (heart, brain, or muscle).
CH3-C-S-CoA
O
Acetyl CoA
CH3-C-S-CoA
OCH3-C-CH2-C-O-
O O CH3-C-CH3 + CO2 + energy
O
Acetoacetate
Acetone
-Hydroxybutyrate
CH3-CH-CH2-C-O-
OH O
Ketosis (disease)
- When ketone bodies accumulate and they cannot be metabolized.
- Found in diabetes and in high diet in fat and low in carbohydrates.
- They can lower the blood pH (acidosis).
- Blood cannot carry oxygen and cause breathing difficulties.
Fatty acid synthesis
- When glycogen store is full (no more energy need).
- Excess acetyl CoA convert to 16-C fatty acid (palmitic acid) in cytosol.
- New fatty acids are attached to glycerol to make triacylglycerols. (are stored as body fat)
Metabolism in cell
CarbohydratesPolysaccharides
Proteins
Lipids
GlucoseFructose
Galactose
Amino acids
Glycerol
Fatty acids
Stage 1: Digestion and hydrolysis
Glucose Pyruvate Acetyl CoACitricAcidcycle
CO2 & H2O
UreaNH4
+
Stage 2: Degradationand some oxidation
Stage 3: Oxidation to CO2,H2O and energy
e
e
Mitochondria
(Formation of Acetyl CoA)
Degradation of amino acids
- They are degraded in liver.
Transamination:
- They react with α-keto acids and produce a new amino acid and a new α-keto acid.
-OOC-C-CH2-CH2-COO-
O
alanine
CH3-CH-COO-
NH3
+
+
α-ketoglutarate
-OOC-CH-CH2-CH2-COO-
O
pyruvate
CH3-C-COO-
NH3
+
+
glutamate
Degradation of amino acids
Oxidative Deamination
-OOC-CH-CH2-CH2-COO-
NH3
+
glutamate
+ H2O + NAD+
-OOC-C-CH2-CH2-COO-
O
α-ketoglutarate
glutamatedehydrogenase
+ NH4+ + NADH + H+
Urea cycle
- Ammonium ion (NH4+) is highly toxic.
- Combines with CO2 to produce urea (excreted in urine).
- If urea is not properly excreted, BUN (Blood Urea Nitrogen) level in blood becomes high and it build up a toxic level (renal disease).
- Protein intake must be reduced and hemodialysis may be needed.
H2N-C-NH2 + 2H+ + H2O
O
urea
2NH4+ + CO2
Energy from amino acids
- C from transamination are used as intermediates of the citric acid cycle.
- amino acid with 3C: pyruvate- amino acid with 4C: oxaloacetate- amino acid with 5C: α-ketoglutarate
- 10% of our energy comes from amino acids.
- But, if carbohydrates and fat stores are finished, we take energy from them.