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Metabolic Pathways Overview of metabolism pathways

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1 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

2 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.

3 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.)

4 Major Metabolic Pathways in a Bacterial Cell (M.Shuler, 2002)
End products are formed and released from the cells through these reactions, which are often valuable products for human or animal consumption. e.g. ethanol, amino acids, enzymes, fatty acids, antibodies.

5 Metabolic Pathways Bioenergetics Sunlight
Photosynthesis by autotrophs : CO2 + H2O → carbohydrates Autotrophs or heterotrophs Catabolism generating energy, e.g ATP Anabolism requiring energy

6 Metabolic Pathways Bioenergetics
- Energy is mainly stored or transferred by adenosine triphosphate (ATP). Other energy carrying compounds include GTP, UTP and CTP. Guanosine Triphospohate, Uridine triphosphate and cytidine triphosphate

7 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

8 Nicotinamide Adenine Dinucleotide (NAD+)
2e- , H+

9 Flavin Adenine Dinucleotide (FAD)
2 electrons Isoalloxazine ring

10 Nicotinamide Adenine Dinucleotide Phosphate (NADP+)

11 Review of Metabolism Pathways http://www. genome
Review of Metabolism Pathways Glucose metabolism is the centre of the cell metabolism pathways

12 Embden-Meyerhof-Parnas (EMP)
Glucose Catabolism Glucose Glycolysis or Embden-Meyerhof-Parnas (EMP) Anaerobic metabolism Aerobic metabolism Fermentation: ethanol, acetic acid, lactate. Tricarboxylic acid (TCA) or (Krebs) or (Citric acid cycle) Oxidative phosphorylation

13 Glucose Catabolism Glycolysis

14 Glucose Catabolism Glycolysis
Glycolysis or Embden-Meyerhof-Parnas (EMP) Breakdown of a molecule of g to two pyruvate molecules. - Each pathway is catalyzed by particular enzyme(s) - Generating 2 ATP, 2 NADH and pyruvate (Key Metabolite). - Taking place in cytoplasm

15 a-D-Glucose Pyruvate

16 Glycolysis (EPM) glycogen Amino acid Acetyl-CoA Ethanol Fatty acids
control sites: feedback inhibition glycogen Amino acid Acetyl-CoA Ethanol Fatty acids

17 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

18 Embden-Meyerhof-Parnas (EMP)
Glucose Catabolism Glucose Glycolysis or Embden-Meyerhof-Parnas (EMP) Anaerobic metabolism Aerobic metabolism Fermentation: ethanol, acetic acid, lactate. Tricarboxylic acid (TCA) or (Krebs) or (Citric acid cycle) Oxidative phosphorylation

19 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+.

20 Citric Acid Cycle amino acid synthesis Control site by ATP
NADH generated CO2 released FADH2 generated amino acid synthesis

21 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.

22 Embden-Meyerhof-Parnas (EMP)
Glucose Catabolism Glucose Glycolysis or Embden-Meyerhof-Parnas (EMP) Anaerobic metabolism Aerobic metabolism Fermentation: ethanol, acetic acid, lactate. Tricarboxylic acid (TCA) or (Krebs) or (Citric acid cycle) Respiratory chain: Oxidative phosphorylation

23 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

24 Glucose Catabolism Oxidative Phosphorylation
In the process of Oxidative Phosphorylation In eucaryotes: NADH + H ATP FADH ATP In procaryotes: NADH + H ≤2 ATP FADH2 ATP

25 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

26 Embden-Meyerhof-Parnas (EMP)
Glucose Catabolism Glucose Glycolysis or Embden-Meyerhof-Parnas (EMP) Anaerobic metabolism Aerobic metabolism Fermentation: ethanol, acetic acid, lactate. Tricarboxylic acid (TCA) or (Krebs) or (Citric acid cycle) Respiratory chain: Oxidative phosphorylation

27 Glucose Anaerobic Catabolism
Glycolysis (EMP)

28 Hydrocarbon Catabolism
Hydrocarbon: C & H - Aliaphatic hydrocarbon e.g. octane, C8H18 polyethylene –HC=CH- - Aromatic hydrocarbon 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 naphthalene

29 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

30 Photosynthesis Glycolysis and TCA

31 Overview of Biosynthesis
Pentose-phosphate pathway (hexo-monophosphate pathway (HMP): convert glucose-6-phosphate into a carbon skeletons of C3 ~ C7 . Polysaccharides: glycan, glycogen gluconeogenesis Lipids Proteins Nucleic acids (DNAs, RNAs)

32 2 1 5 3 4 6

33 Summary of Metabolism Pathways
- catabolism: ATP, C skeleton for further biosynthesis - anabolism: biosynthesis requiring energy Bioenergetics: - energy storage and carrier ATP - Reducing power carriers: NADH, NADPH, FADH

34 Summary of Metabolism Pathways
Glucose catabolism: Glucose Anaerobic metabolism Tricarboxylic acid (TCA) or (Krebs) or (Citric acid cycle) Respiratory chain: Oxidative phosphorylation Glycolysis or Embden-Meyerhof-Parnas (EMP) Fermentation: ethanol, acetic acid, lactate. Aerobic metabolism

35 Summary of Metabolism Pathways
Nitrogen compound catabolism Hydrocarbon catabolism Photosynthesis Biosynthesis


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