Transcript Document

Chemistry 20
Chapter 19 & 20
Metabolic pathway & Energy production
Metabolism
Chemical reactions in cells that break down or build molecules.
It produces energy and provide substances to cell growth.
Catabolic reactions:
Complex molecules  Simple molecules + Energy
Anabolic reactions:
Simple molecules + Energy (in cell)  Complex molecules
Metabolism in cell
Mitochondria
Proteins
Urea
NH4+
Amino acids
e
Carbohydrates
Polysaccharides
Glucose
Fructose
Galactose
Glucose
Pyruvate
Acetyl CoA
Citric
Acid
cycle
e
CO2 & H2O
Glycerol
Lipids
Fatty acids
Step 1:
Digestion
and hydrolysis
Step 2: Degradation
and some oxidation
Step 3:
Oxidation to CO2,
H2O and energy
Cell Structure
Nucleus
Membrane
Mitochondria
Cytoplasm
(Cytosol)
Cell Structure
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).
Mitochondria: energy producing factories.
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.
ph os phoric
ester
O O O
O-P-O-P-O-P-O-CH2
O
O O- O
H
H
H
ph os phoric
3 Phosphates
anh yd rides
HO
OH
NH2
N
N
N
aden ine
N
 -N -glycos idic b on d
H
-D-ribofuranose
Ribose
ATP and Energy
O O
O-P-O-P-O-AMP + H2 O
O O
ATP
O
O-P-O-AMP + H2 PO4 + 7.3 kcal/mol
O
AD P
(adenosine triphosphate)
Pi
(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
Step 1: Digestion
Convert large molecules to smaller ones
that can be absorbed by the body.
Carbohydrates
Lipids (fat)
Proteins
Digestion: Carbohydrates
Salivary
amylase
Mouth
Dextrins
+
Polysaccharides
+
Maltose
Stomach
Small intestine
pH = 8
pH = 2 (acidic)
Dextrins
α-amylase
(pancreas)
Maltose
Lactose
Sucrose
Bloodstream
Glucose
Maltase
Lactase
Sucrase
Glucose
Glucose
+
Galactose
Glucose
+
Fructose
Liver (convert all to glucose)
Glucose
+
Digestion: Lipids (fat)
Small intestine
H2C
Fatty acid
HC
Fatty acid
H2C
Fatty acid
+ 2H2O
Triacylglycerol
H2C
lipase
(pancreas)
OH
H2C
OH
HC
Fatty acid + 2 Fatty acids
Monoacylglycerol
Intestinal wall
Monoacylglycerols + 2 Fatty acids → Triacylglycerols
Protein
Lipoproteins
Chylomicrons
Lymphatic system
Bloodstream
Cells
Enzymes hydrolyzes
Glycerol + 3 Fatty acids
liver
Glucose
Digestion: Proteins
Pepsinogen
HCl
Pepsin
Stomach
Proteins
denaturation + hydrolysis
Polypeptides
Small intestine
Typsin
Chymotrypsin
Polypeptides
Intestinal wall
Bloodstream
Cells
hydrolysis
Amino acids
Some important coenzymes
oxidation Coenzyme + Substrate
Coenzyme(+2H) + Substrate(-2H)
Reduced
2 H atoms
2H+ + 2e-
NAD+
Coenzymes
Oxidized
FAD
Coenzyme A
NAD+
Nicotinamide adenine dinucleotide
The p lus sign on N A D +
represents th e positive
ch arge on this n itrogen
O
CNH2
O
-
O-P-O-CH2
O
ADP
AMP H
N+
O
H
H
H
HO
N icotinamide;
derived
from niacin (vitamin)
OH
Ribose
a -N-glycosidic
bond
NAD+
- Is a oxidizing agent.
- Participates in reactions that produce (C=O) such as
oxidation of alcohols to aldehydes and ketones.
O
CH3-CH2-OH + NAD+
CH3-C-H + NADH + H+
NAD+ + 2H+ + 2e-  NADH + H+
H
NH2 + H+ + 2 e-
N
Ad
NAD+
H H O
C
NH2
:
+
O
C
N
Ad
N AD H
FAD
Flavin adenine dinucleotide
O
H3 C
N
H3 C
N
N
N
Riboflavin
CH2
(Vitamin B2)
H C OH
H C OH
H C OH
CH2
O
O=P-O-AMP
OADP
H
Flavin
O
Ribitol (sugar alcohol)
FAD
- Is a oxidizing agent.
- Participates in reaction that produce (C=C) such as
dehydrogenation of alkanes.
H H
R-C-C-R + FAD
HH
R-C=C-H + FADH2
H H
O
H3 C
H3 C
N
N
N
Ad
FAD
NH
O
H3 C
H
N
O
+ 2 H+ + 2 e H3 C
N
N
Ad H
FAD H2
NH
O
Coenzyme A (CoA)
HS-CoA
Coenzyme A
Aminoethanethiol
( vitamin B5)
Coenzyme A (CoA)
- It activates acyl groups, particularly the acetyl group.
O
O
CH3-C- + HS-CoA
CH3-C-S-CoA
Acetyl group Coenzyme A
Acetyl CoA
Metabolism in cell
Mitochondria
Proteins
Urea
NH4+
Amino acids
e
Carbohydrates
Polysaccharides
Glucose
Fructose
Galactose
Glucose
Pyruvate
Acetyl CoA
Citric
Acid
cycle
e
CO2 & H2O
Glycerol
Lipids
Fatty acids
Step 1:
Digestion
and hydrolysis
Step 2: Degradation
and some oxidation
Step 3:
Oxidation to CO2,
H2O and energy
Step 2: Glycolysis
- 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).
2 ADP + 2Pi
2 ATP
C6H12O6 + 2 NAD+
O
2CH3-C-COO- + 2 NADH + 4H+
Glucose
Pyruvate
Inside of cell
Pathways for pyruvate
- Pyruvate can produce more energy.
Aerobic conditions: if we have enough oxygen.
Anaerobic conditions: if we do not have enough oxygen.
Aerobic conditions
- Pyruvate is oxidized and a C atom remove (CO2).
- Acetyl is attached to coenzyme A (CoA).
- Coenzyme NAD+ is required for oxidation.
OO
O
CH3-C-C-O- + HS-CoA + NAD+
pyruvate
Coenzyme A
CH3-C-S-CoA + CO2 + NADH
Acetyl CoA
Important intermediate product
in 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.
OO
CH3-C-C-O-
NADH + H+
NAD+
HO O
CH3-C-C-OH
pyruvate
Lactate
Reduced
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
Mitochondria
Proteins
Urea
NH4+
Amino acids
e
Carbohydrates
Polysaccharides
Glucose
Fructose
Galactose
Glucose
Pyruvate
Acetyl CoA
Citric
Acid
cycle
e
CO2 & H2O
Glycerol
Lipids
Fatty acids
Step 1:
Digestion
and hydrolysis
Step 2: Degradation
and some oxidation
Step 3:
Oxidation to CO2,
H2O and energy
Step 3: Citric Acid 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
O
Acetyl CoA
CH3-C-S-CoA
+
COOC=O
Oxaloacetate
CH2
COO-
COOCH2
H2O
HO
C
COO-
+ CoA-SH
CH2
COOCitrate
Coenzyme A
Reaction 2
Isomerisation to Isocitrate
- Because the tertiary –OH cannot be oxidized.
(convert to secondary –OH)
HO
COO-
COO-
CH2
CH2
C
COO-
CH2
COOCitrate
Isomerisation
H
C
COO-
HO
C
H
COOIsocitrate
Reaction 3
First oxidative decarboxylation (CO2)
- Oxidation (-OH converts to C=O).
- NAD+ is reduced to NADH.
- A carboxylate group (-COO-) is removed (CO2).
H
HO
COO-
COO-
COO-
CH2
CH2
CH2
C
CH2 -COO- - NAD + NADH + H+
COO-
H C-COO
H
COO-
C
i socitrate
H COO O
CHO CHC
de hydroge nase
Isocitrate
-COOCOO
- CO
CH
-COO
CH2 -COO
2
2
Isocitrate
H C-COO -
CH2
CO2
O
C
COO-
α-Ketoglutrate
H C-H
-
Reaction 4
Second oxidative decarboxylation (CO2)
- Coenzyme A convert to succinyl CoA.
- NAD+ is reduced to NADH.
- A second carboxylate group (-COO-) is removed (CO2).
COOCH2
2
CHCH
-COO
2
O CHC
2
COO-O C-COO
α-Ketoglutrate
-Ketoglu
tarate
COOCH2
CoA -SH
N AD +
CH2 CH2 -COO
+ CO
O
C
CH
+ CO 2 2
2
-ke togl u tarate
S-CoA
de h ydroge n as e O C SCoA
S u cciSuccinyl
n yl -C CoA
oA
com ple x
N AD H
Reaction 5
Hydrolysis of Succinyl CoA
- Energy from hydrolysis of succinyl CoA is used to add a phosphate
group (Pi) to GDP (guanosine diphosphate).
- Phosphate group (Pi) add to ADP to produce ATP.
COO-
COO-
CH2
CH2
O
CH2 -COO
+ Pi
FAD
- ADP
+ H2O + GDP + Pi
C
CH2 -COO Succi nate
HCH COOC2
ATP 2
FADH
succinate
de hydroge nase
-
C
OOC
CH H
2
Fumarate
COO-
S-CoA
Succinyl CoA
Succinate
+ GTP + CoA-SH
Reaction 6
Dehydrogenation of Succinate
- H is removed from two carbon atoms.
- Double bond is produced.
- FAD is reduced to FADH2.
COOCH2
CH2 -COO CH2
CH2 -COO COO
Succi nate
Succinate
COOFAD
H
FADH2
s uccinate
de hydroge nas e
-
C
CH COO
C CH
OOC
H
COOFumarate
Fumarate
Reaction 7
Hydration
- Water adds to double bond of fumarate to produce malate.
COOCH
CH
COOFumarate
H 2O
COOHO
C
H
CH2
COOMalate
Reaction 8
Dehydrogenation forms oxaloacetate
- -OH group in malate is oxidized to oxaloacetate.
- Coenzyme NAD+ is reduced to NADH + H+.
COOHO
CHCOO
H
HO C
CH2 -COO CH2
L-Malate
COOMalate
COONAD + N ADH + HO+ C-COO
C=O
CH2CH
-COO mal ate
2
de h ydroge n as e O xaloacetate
COO-
Oxaloacetate
Summary
The catabolism of proteins, carbohydrates, and fatty acids
all feed into the citric acid cycle at one or more points:
Prote in s
C arboh ydrate s
Fatty Acids
Pyru vate
Ace tyl-C oA
O xal oace tate
-Ketoglu tarate i nte rme di ate s
S u cci n yl-C oA of th e ci tric
Fu marate
aci d cycl e
Mal ate
Summary
Ace tyl-C oA
C oA
H + + N AD H
N AD +
C i tri c
aci d
cycl e
(8 ste ps)
C oA
FAD H2
N AD +
N AD H + H +
CO 2
N AD +
FAD
GTP
GDP
N AD H + H +
CO 2
O
CH3 C-SCo A + GDP + Pi + 3 NAD + + FAD + 2 H2 O
2 CO2 + CoA + GT P + 3 NADH + FADH2 + 3 H+
12 ATP produced from each acetyl-CoA
Electron Transport
H+ and electrons from NADH and FADH2 are carried by an electron carrier
until they combine with oxygen to form H2O.
FMN (Flavin Mononucleotide)
Fe-S clusters
Electron carriers
Coenzyme Q (CoQ)
Cytochrome (cyt)
FMN (Flavin Mononucleotide)
H
O
Riboflavin
(Vitamin B2)
H3 C
N
H3 C
N
N
N
O
H
Flavin
O
2H+ + 2e-
CH2
H3 C
N
H3 C
N
Riboflavin
H C OH
H C OH
H C OH
CH2
N
N
H C OH
CH2
O
O=P-O-AMP
O
O=P-O-AMP
-
-
O
O
FMN + 2H+ + 2e- → FMNH2
Reduced
Flavin
O
CH2 H
H C OH
H C OH
Ribitol
(sugar alcohol)
H
Ribitol
Fe-S Clusters
Cys
S
S
S
Cys
S
+ 1 e-
Fe3+
Cys
Cys
S
Cys
Fe3+ + 1e-
S
Cys
S
Cys
Fe2+
Cys
S
Fe2+
Reduced
Coenzyme Q (CoQ)
OH
2H+ + 2e-
OH
Coenzyme Q
Reduced Coenzyme Q (QH2)
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+ + 1eOxidized
Fe2+
Reduced
cyt b, cyt c1, cyt c, cyt a, cyt a3
Electron Transfer
Mitochondria
Electron Transfer
Complex I
NADH + H+ + FMN → NAD+ + FMNH2
FMNH2 + Q → QH2 + FMN
NADH + H+ + Q → QH2 + NAD+
Complex II
FADH2 + Q → FAD + QH2
Electron Transfer
Complex III
QH2 + 2 cyt b (Fe3+) → Q + 2 cyt b (Fe2+) + 2H+
Complex IV
4H+ + 4e- + O2 → 2H2O
Oxidative Phosphorylation
Transport of electrons produce energy to convert ADP to ATP.
ADP + Pi + energy → ATP
Chemiosmotic model
- H+ make inner mitochondria acidic.
- Produces different proton gradient.
- H+ pass through ATP synthase (a protein complex).
ATP synthase
Total ATP
Glycolysis:
6 ATP
Pyruvate:
6 ATP
Citric acid cycle:
24 ATP
Oxidation of glucose
36 ATP
C6H12O6 + 6O2 + 36 ADP + 36 Pi → 6CO2 + 6H2O + 36 ATP
Metabolism in cell
Mitochondria
Proteins
Urea
NH4+
Amino acids
e
Carbohydrates
Polysaccharides
Glucose
Fructose
Galactose
Glucose
Pyruvate
Acetyl CoA
Citric
Acid
cycle
e
CO2 & H2O
Glycerol
Lipids
Fatty acids
Step 1:
Digestion
and hydrolysis
Step 2: Degradation
and some oxidation
Step 3:
Oxidation to CO2,
H2O and energy
Oxidation of fatty acids

α
O
CH3-(CH2)14-CH2-CH2-C-OH
 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.
O
O
R-CH2-C-OH + ATP + HS-CoA
Fatty acid
R-CH2-C-S-CoA + H2O + AMP + 2Pi
Fatty acyl CoA
-Oxidation: 4 reactions
Reaction 1: Oxidation (dehydrogenation)
HHO
O
H
R-CH2-C-C-C-S-CoA + FAD
H H
R-CH2-C=C-C-S-CoA + FADH2
H
Fatty acyl CoA
Reaction 2: Hydration
O
H
R-CH2-C=C-C-S-CoA + H2O
H
HO H O
R-CH2-C-C-C-S-CoA
H H
Reaction 3: Oxidation (dehydrogenation)
HO H O
O
R-CH2-C-C-C-S-CoA + NAD+
O
R-CH2-C-CH2-C-S-CoA + NADH+ H+
H H
Reaction 4: Cleavage of Acetyl CoA
O
O
R-CH2-C-CH2-C-S-CoA + CoA-SH
O
O
R-CH2-C-S-CoA + CH3-C-S-CoA
Fatty acyl CoA
Acetyl CoA
Oxidation of fatty acids
One cycle of -oxidation
O
R-CH2-CH2-C-S-CoA + NAD+ + FAD + H2O + CoA-SH
O
O
R-C-S-CoA + CH3-C-S-CoA + NADH + H+ + FADH2
Fatty acyl CoA
# of Acetyl CoA =
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).
O
CH3-C-S-CoA
O
CH3-C-S-CoA
Acetyl CoA
Acetone
O
O
O
CH3-C-CH2-C-O-
CH3-C-CH3 + CO2 + energy
OH
Acetoacetate
O
CH3-CH-CH2-C-O-Hydroxybutyrate
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
Mitochondria
Proteins
Urea
NH4+
Amino acids
e
Carbohydrates
Polysaccharides
Glucose
Fructose
Galactose
Glucose
Pyruvate
Acetyl CoA
Citric
Acid
cycle
e
CO2 & H2O
Glycerol
Lipids
Fatty acids
Step 1:
Digestion
and hydrolysis
Step 2: Degradation
and some oxidation
Step 3:
Oxidation to CO2,
H2O and energy
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.
+
NH3
CH3-CH-COO-
O
+
+
NH3
O
pyruvate
2-CH2-COO
α-ketoglutarate
alanine
CH3-C-COO-
-OOC-C-CH
+
-OOC-CH-CH -CH -COO2
2
glutamate
Degradation of amino acids
Oxidative Deamination
+
NH3
-OOC-CH-CH -CH -COO2
2
+ H2O + NAD+
glutamate
dehydrogenase
glutamate
O
-OOC-C-CH
2-CH2-COO
α-ketoglutarate
+ 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.
O
2NH4+ + CO2
H2N-C-NH2 + 2H+ + H2O
urea
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.