Metabolic Pathways
- Overview of metabolism pathways
- Catabolism
- Anabolism
- Bioenergetics
- Important metabolic pathways
- Catabolism:
- Glucose catabolism
- aerobic pathway
- anaerobic pathway
- Hydrocarbon
- Nitrogen compounds
- Anabolism:
- Photosynthesis
- Biosynthesis
Metabolic Pathways
M
: a complete set of chemical reactions
that occur in living cells, allowing cells to grow
and reproduce, maintain their structures, and
respond to their environments.
Major challenges in bioprocess development:
To select an organism that can efficiently make a
given product
or
digest wastes in the Environment.
It is important to understand the metabolic
pathways.
Metabolic Pathways
- Overview of metabolism pathways
Metabolism can be subdivided by
-C
: The intracellular process of
degrading a compound into smaller and simpler
products and generating energy.
Glucose to CO2, and H2O, protein to amino
acids.
-A
: the synthesis of more complex
compounds and requires energy.
Synthesis of small molecules (amino acids, nucleotides,
fatty acids and sugars) and complex compounds (glycan
(polysaccharide), DNA, RNA, and lipids.)
Major Metabolic Pathways in a
Bacterial Cell (M.Shuler, 2002)
Metabolic Pathways
- Bioenergetics
Autotrophs
or heterotrophs
Sunlight
Photosynthesis by autotrophs :
CO2 + H2O → carbohydrates
Catabolism
generating energy,
e.g ATP
Anabolism
requiring energy
Metabolic Pathways
- Bioenergetics
- Energy is mainly stored or transferred by
adenosine triphosphate (ATP).
Other energy carrying compounds include
GTP, UTP and CTP.
Metabolic Pathways
Bioenergetics
- Reducing power: supply hydrogen atom in
biosynthesis.
• Nicotinamide Adenine Dinucleotide (NADH)
• Flavin Adenine Dinucleotide (FADH2)
NADH and FADH2 are major electron carriers in the
oxidation of fuel molecules and for ATP generation.
• Nicotinamide Adenine Dinucleotide Phosphate
(NADPH).
major electron donor in reductive biosynthesis, e.g
photosynthesis
Nicotinamide Adenine Dinucleotide
(NAD+)
2e- , H+
Flavin Adenine Dinucleotide (FAD)
2 electrons
Isoalloxazine ring
Nicotinamide Adenine Dinucleotide
Phosphate (NADP+)
Review of Metabolism Pathways
http://www.genome.jp/kegg/pathway/map/map01100.html
Glucose metabolism is the centre of the cell metabolism
pathways
Glucose Catabolism
Glucose
Glycolysis or
Embden-Meyerhof-Parnas (EMP)
Aerobic metabolism
Anaerobic metabolism
Fermentation: ethanol,
acetic acid, lactate.
Tricarboxylic acid (TCA)
or (Krebs)
or (Citric acid cycle)
Oxidative phosphorylation
Glucose Catabolism
Glycolysis
• http://www.science.smith.edu/department
s/Biology/Bio231/glycolysis.html
Glucose Catabolism
Glycolysis
• Glycolysis or Embden-Meyerhof-Parnas
(EMP)
Breakdown of a molecule of g
two pyruvate molecules.
to
- Each pathway is catalyzed by particular
enzyme(s)
- Generating 2 ATP, 2 NADH and
2 pyruvate (Key Metabolite).
- Taking place in cytoplasm
a-D-Glucose
Pyruvate
Glycolysis (EPM)
glycogen
Amino acid
Acetyl-CoA
Ethanol
Fatty acids
Amino acid
control sites:
feedback inhibition
Glucose Catabolism
Glycolysis
• The overall reaction in glycolysis is:
Glucose + 2ADP + 2 NAD+ + 2 Pi →2 pyruvate +
2 ATP+ 2 (NADH + H+)
Produce
- e
;
- Key metabolite: pyruvate
Glucose Catabolism
Glucose
Glycolysis or
Embden-Meyerhof-Parnas (EMP)
Aerobic metabolism
Anaerobic metabolism
Fermentation: ethanol,
acetic acid, lactate.
Tricarboxylic acid (TCA)
or (Krebs)
or (Citric acid cycle)
Oxidative phosphorylation
Glucose Catabolism
Krebs, Tricarboxylic Acid (TCA), or Citric
Acid Cycle
• Under a
conditions
• Taking place
- in mitochondria in eucaryotes
- associated with membrane-bound
enzymes in procaryotes
• Pyruvate produced in glycolysis (EMP) pathway
transfer its reducing power to NAD+.
http://www.science.smith.edu/departments/Biology/Bio231/krebs.html
amino acid synthesis
Control site by ATP
NADH generated
CO2 released
FADH2 generated
Citric Acid Cycle
amino acid synthesis
Glucose Catabolism
Citric Acid Cycle
The overall reaction of TCA cycle:
acetyl-CoA + 3 NAD + FAD + Pi + 2H2O → CoA + 3(NADH + H+)
+FADH2+GTP+ 2CO2
• Intermediate products such as oxylacetate and
α–ketoglutarate are used as precursors for the
synthesis of certain amino acids.
• The reducing power (NADH + H+ and FADH2) is used
for biosynthesis pathway or for ATP generation
through the electron transport chain.
Glucose Catabolism
Glucose
Glycolysis or
Embden-Meyerhof-Parnas (EMP)
Aerobic metabolism
Anaerobic metabolism
Fermentation: ethanol,
acetic acid, lactate.
Tricarboxylic acid (TCA)
or (Krebs)
or (Citric acid cycle)
Respiratory chain:
Oxidative phosphorylation
Glucose Catabolism
Respiratory Chain-Oxidative Phosphorylation
“Oxidative Phosphorylation is the electron transport
chain that forms ATP as electrons are transferred
from NADH or FADH2 to o
by a series of
electron carriers” (L. Stryer, 1988)
-
-
electron acceptor: oxygen (aerobic condition)
generate ATP, H2O
from NADH or FADH2
Taking place in mitochondria in eucaryotes
or in cytoplasmic membrane in procaryotes
http://www.brookscole.com/chemistry_d/templates/student_resources/shared_resources/animations/oxidative/oxidativephosphorylation.html
Glucose Catabolism
Oxidative Phosphorylation
• In the process of Oxidative Phosphorylation
In eucaryotes:
NADH + H+
FADH2
3 ATP
2 ATP
In procaryotes:
NADH + H+
FADH2
≤2 ATP
ATP
Glucose Aerobic Catabolism
Reaction Summary
• EMP (glycolysis)
Glucose + 2ADP + 2 NAD+ + 2 Pi →2 pyruvate + 2 ATP+ 2 (NADH + H+)
• Entry of pyruvate
2pyruvate + 2NAD+ + 2CoA-SH →2 acetyl-CoA + 2CO2 + 2(NADH + H+)
• TCA cycle
2acetyl-CoA + 6 NAD + 2FAD + 2GDP+ 2Pi + 4H2O → 2CoA + 6(NADH
+ H+) +2FADH2+2GTP (~ATP) + 4CO2
• Oxidative Phosphorylation
In eucaryotes
EMP: 2 NADH → 2 FADH2 → 4 ATP (glycerol phosphate shuttle)
Entry of pyruvate and TCA: 8 NADH → 24 ATP
TCA: 2FADH2 → 4 ATP
The overall reaction:
Glucose + 6O2 + 36ADP + 36 Pi → 6 CO2 + 6 H2O + 36 ATP
Glucose Catabolism
Glucose
Glycolysis or
Embden-Meyerhof-Parnas (EMP)
Aerobic metabolism
Anaerobic metabolism
Fermentation: ethanol,
acetic acid, lactate.
Tricarboxylic acid (TCA)
or (Krebs)
or (Citric acid cycle)
Respiratory chain:
Oxidative phosphorylation
Glucose Anaerobic Catabolism
Glycolysis (EMP)
Hydrocarbon Catabolism
• Hydrocarbon: C & H
Aliaphatic hydrocarbon
e.g. octane, C8H18
polyethylene –HC=CHAromatic hydrocarbon
naphthalene
naphthalene
• Metabolism of hydrocarbon
Requires oxygen
Hydrocarbons are converted to acetyl-CoA which is
metabolized by TCA cycle.
Challenges : low solubility in aqueous solution.
available microorganisms are limited
Pseudomonas, Mycobacteria
Nitrogen Compounds Catabolism
Nitrogen compounds can be used for C, N and energy
sources
Proteins → peptides → amino acids → converted to
other amino acids or organic acids and ammonia by
deamination.
- organic acids: acetyl-CoA into TCA cycle, lipids
- amino acids: proteins, other amino acids or enter
TCA cycle
- ammonium: amino acid, protein, nucleic acids
Nucleic acids → ribose/deoxyribose, phosphoric acid
and purine/pyrimidine
- sugar: glycolysis and TCA
- Phosphoric acid: ATP, lipids, nucleic acids
- bases: nucleic acids, urea, acetic acids
Photosynthesis
Glycolysis and TCA
Overview of Biosynthesis
• Pentose-phosphate pathway (hexomonophosphate pathway (HMP):
convert glucose-6-phosphate into a carbon
skeletons of C3 ~ C7 .
• Polysaccharides: glycan, glycogen
gluconeogenesis
• Lipids
• Proteins
• Nucleic acids (DNAs, RNAs)
2
1
5
3
4
6
Summary of Metabolism Pathways
• Metabolism:
- catabolism: ATP, C skeleton for further
biosynthesis
- anabolism: biosynthesis requiring energy
• Bioenergetics:
- energy storage and carrier ATP
- Reducing power carriers: NADH,
NADPH, FADH
Summary of Metabolism Pathways
• Glucose catabolism:
Glucose
Glycolysis or
Embden-Meyerhof-Parnas (EMP)
Aerobic metabolism
Anaerobic metabolism
Fermentation: ethanol,
acetic acid, lactate.
Tricarboxylic acid (TCA)
or (Krebs)
or (Citric acid cycle)
Respiratory chain:
Oxidative phosphorylation
Summary of Metabolism Pathways
•
•
•
•
Nitrogen compound catabolism
Hydrocarbon catabolism
Photosynthesis
Biosynthesis