Chemistry B11
Chapter 27 & 28
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
Stage 1:
Digestion
and hydrolysis
Stage 2: Degradation
and some oxidation
(Formation of Acetyl CoA)
Stage 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
Stage 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
Trypsin
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
H
H
HO
(Vitamin B3)
N+
O
H
N icotinamide;
derived
from niacin (vitamin)
OH
Ribose
a -N-glycosidic
bond
NAD+
- Is an 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
O
C
NH2 + H+ + 2 e-
NH2
:
+
H H O
C
N
Ad
NAD
+
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
-
O
ADP
H
Flavin
O
Ribitol (sugar alcohol)
FAD
- Is an 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)
Coenzyme A
Aminoethanethiol
( vitamin B5)
Coenzyme A (CoA)
O
O
- It activates acyl groups (RC-), particularly the Acetyl group (CH3C-).
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
Stage 1:
Digestion
and hydrolysis
Stage 2: Degradation
and some oxidation
(Formation of Acetyl CoA)
Stage 3:
Oxidation to CO2,
H2O and energy
Stage 2: Formation of Acetyl CoA
Glycolysis: Oxidation of glucose
- 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
C6H12O6 + 2 NAD+
2 ATP
O
2CH3-C-COO- + 2 NADH + 4H+
Glucose
Pyruvate
Inside of cell (Cytoplasm)
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
Stage 1:
Digestion
and hydrolysis
Stage 2: Degradation
and some oxidation
(Formation of Acetyl CoA)
Stage 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
COO-
C
H C-COO
isocitrate
H COO - dehydrogenase
O
CHO CHC
Isocitrate
-COOCOO
- CO
CH
-COO
CH2 -COO
2
2
Isocitrate
H C-H
H C-COO -
-
CH2
CO2
O
C
COO-
α-Ketoglutrate
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
-Ketoglutarate
COOCH2
CoA -SH
N AD +
N AD H
-ketoglutarate
dehydrogenase
complex
CH2 CH2 -COO
+ CO
O
C
CH
+ CO 2 2
2
S-CoA
O C SCoA
Succinyl CoA
Succinyl-CoA
Reaction 5
Hydrolysis of Succinyl CoA
- 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.
GTP + ADP → GDP+ ATP
COOCH2
CH2 + H2O + GDP + Pi
O
C
COOCH2
CH2
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 CHCH
2
-COO 2
COO
Succinate
Succinate
COOFAD
H
FAD H2
succinate
dehydrogenas 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
COON AD + N AD H + HO+ C-COO
C=O
CH2CH
-COO malate
2
dehydrogenase
OxaloacetateCOO
Oxaloacetate
Summary
The catabolism of proteins, carbohydrates, and fatty acids
all feed into the citric acid cycle at one or more points:
Citric Acid
Cycle
Summary
Summary
Summary
The main function of the citric acid cycle is to produce reduced
coenzymes (NADH and FADH2).
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
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
N
N
H C OH
CH2
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
Aerobic
4H+ + 4e- + O2 → 2H2O
From reduced coenzymes
or the matrix
From the electron
transport chain
From inhaled air
Oxidative Phosphorylation
Transport of electrons produce energy to convert ADP to ATP.
ADP + Pi + energy → ATP + H2O
Chemiosmotic model
- H+ make inner mitochondria acidic.
- Produces different proton gradient.
- H+ pass through ATP synthase (a protein complex).
ATP synthase
Total ATP
Glycolysis:
7 ATP
Oxidation of Pyruvate:
5 ATP
Citric acid cycle:
20 ATP
Oxidation of glucose
32 ATP
C6H12O6 + 6O2 + 32 ADP + 32 Pi → 6CO2 + 6H2O + 32 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
R-CH2-C-C-C-S-CoA + FAD
H H
R-CH2-C=C-C-S-CoA + FADH2
H H
Fatty acyl CoA
Reaction 2: Hydration
O
R-CH2-C=C-C-S-CoA + H2O
H 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
Stage 1:
Digestion
and hydrolysis
Stage 2: Degradation
and some oxidation
(Formation of Acetyl CoA)
Stage 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.