3/22/2012

Topic 9: Introduction to Metabolism

Molecules and Life

Topic 9: Introduction to Metabolism

Dynamic Function of Biomolecules Storage and Transfer of Biological Information

Dr. Tey lai Hock

Dr. Tey lai Hock

Molecules and Life

Amino acids and Proteins
Classification of amino acids Properties of amino acids Polypeptides and proteins

Molecules and Life

Protein structure and Function

Enzymes Structural proteins Transport and storage proteins Four levels of protein structure/configuration Studying protein structure and function
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3/22/2012

Dynamic Functions of Biomolecules

Enzymes
Introduction and catalytic properties of enzymes Naming of enzymes The kinetic properties of enzymes Substrate binding, inhibition and enzyme action

Dynamic Functions of Biomolecules

Myoglobin 153/154 amino acids @ Mw =16,700 .

Carbohydrates
Monosaccharide(s) Carbohydrates structure and reaction Polysaccharides Glycoproteins
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Dynamic Functions of Biomolecules

Lipids

Dynamic Functions of Biomolecules

Fatty acids and structure Nonpolar and polar lipids Steroids and other lipids

Example of fatty acid; Butanoic acid

Biological Membranes

Biological roles of membranes and their structures Membrane transport Examples of membrane transport

Dr. Tey lai Hock

Dr. Tey lai Hock

3/22/2012

Storage and Transfer of Biological Information

The nucleic acids: DNA and RNA
DNA and RNA chemical structures DNA and RNA structural elements Nucleic acid-protein complexes

Storage and Transfer of Biological Information

Protein synthesis: Translation and the Genetic code

The process of protein synthesis The three stages of protein synthesis Post-translational processing of proteins Regulation of protein synthesis and gene expression

Dr. Tey lai Hock

Dr. Tey lai Hock

Storage and Transfer of Biological Information

Storage and Transfer of Biological Information

Dr. Tey lai Hock

Dr. Tey lai Hock

3/22/2012

Introduction to Metabolism

Metabolism
Introduction to metabolism
Living organisms are not at equilibrium. Require a continuous influx of free energy to maintain order in a universe bent on maximizing disorder. Metabolism: Sum total of all chemical reactions in an organism. They do so by coupling the exergonic reactions of nutrient oxidation to the endergonic processes required to maintain the living state, such as the performance of mechanical network, the active transport of molecules against concentration gradients, and the biosynthesis of complex molecules.
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Metabolism
Introduction to metabolism
Exergonic reaction: Is a chemical reaction, where the change in the Gibbs free energy is negative, indicating a spontaneous reaction. Endergonic reaction: Is a chemical reaction, where the standard free energy change is positive, and energy is absorbed. It is also known as unfavorable reaction or nonspontaneous reaction.

Metabolism
Exergonic reaction: G = Gproducts - Greactants < 0

Endergonic reaction: Standard free energy change G = G + RTlnK

When K = 1

G > 0

G = G + RTln1 G = G
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3/22/2012

Metabolism

Metabolism
Introduction to metabolism
Metabolic differences among organisms are divided into two major classes; Autotrophs (Self-feeding organisms): Use atmospheric carbon dioxide (CO2) to build complex carbon-containing biomolecules. Heterotrophs (feeding on others): Obtain energy by ingesting complex carbon-containing compounds such as carbohydrates and fats.

Dr. Tey lai Hock

Dr. Tey lai Hock

Metabolism

Metabolism
Introduction to metabolism
Cells must synthesize new complex substances. Thousands of such reactions occurring simultaneously in a single cell. Divided into two parts: Catabolism: Degradation, in which nutrients and cell constituents are broken down to generate energy. Anabolism: Biosynthesis, in which biomolecules are synthesized from simpler components and energy is used.
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Metabolism
Metabolic processes in heterotrophic cells.

Metabolism
Anabolism
Formation or synthesis of new molecules; Inorganic/organic molecules glucose, amino acids, fatty acids carbohydrates, proteins, fats

Dr. Tey lai Hock

Dr. Tey lai Hock

Metabolism
Catabolism
Breakdown or degradation of larger molecules into simple molecules; Carbohydrates, proteins, fats glucose, amino acids, fatty acids Inorganic/organic products, and energy

Metabolism
(Oxidative, exergonic)

(Reductive, endergonic)

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Dr. Tey lai Hock

3/22/2012

Metabolism
What is ATP?
Adenosine-5-triphosphate (ATP) is a multifunctional nucleotide used in cells as a coenzyme. It is often called the molecular unit of currency of intracellular energy transfer. ATP transport chemical energy within cells for metabolism.
Phosphoester bond

Metabolism

Dr. Tey lai Hock

ATP hydrolysis/dephosphorylation. The overall charges for ATP and ADP is at physiological pH is -3.5 and -2.5, respectively. Each of the phosphorus atoms are highly electrophilic and can react with nucleophiles like OH of water or an alcohol. The G for the hydrolysis process is -7.5 kcal/mol (7.5*4.18 = 31.35 kJ/mol).

Dr. Tey lai Hock

Metabolism

Metabolic pathway
Introduction
Metabolic pathway are series of consecutive enzymatic reactions that produce specific products (also referred to as metabolites), energy, structural components and etc. [e.g. degradation of glucose to pyruvate (glycolysis)]. Through the metabolic pathway, we are able to study how free energy is consumed in building cellular materials and carrying out cellular work. Other than that, able to study how free energy is generated from organic or other sources.
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Human is the sample of battery!

3/22/2012

Metabolic pathway
Introduction
Four major components/biomolecules that deal with metabolic pathway Carbohydrates -Glycolysis, gluconeogenesis. Amino acids and Proteins -Nitrogen cycle and fixation, urea cycle Lipids -Fatty acid oxidation, lipogenesis Nucleotides -Biosynthesis of purines and pyrimidines
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Metabolic pathway

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Metabolic pathway
Types of pathways A) Linear metabolic pathways
- Series of independent enzymes catalyzed reactions. In which the product of one reaction is the substrate for next reaction. e.g. Glycolysis pathway. Glucose Glucose-6-phosphate Fructose-6-phosphate Glyceraldehyde-3-phosphate Pyruvate

Metabolic pathway
Types of pathways B) Non-linear metabolic pathways
1) Cyclic pathway - Sequence of enzyme catalyzed steps but the sequence follows a closed loop. e.g. Citric acid cycle / Tricarboxylic acid cycle/ Krebs cycle 2) Spiral pathway - Same sets of enzymes is used to repeatedly lengthening or shortening of a given molecule. e.g. Fatty acid degradation/ -oxidation .
Dr. Tey lai Hock

Dr. Tey lai Hock

3/22/2012

Metabolic pathway

Metabolic pathway

Dr. Tey lai Hock

Dr. Tey lai Hock

Metabolic pathway

Deciphering metabolic pathway

Types of studies
Genetic engineering: Using gene knockouts techniques to inactivated or deleted specific gene to study the particular metabolic pathway. Molecular biology: Prepare cell-free extracts from animals/plants cells. It is homogenized in a buffer to release the components and fractional centrifugation is used to separate organelles. Automated chromatography and electrophoresis procedures may be applied.

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Dr. Tey lai Hock

3/22/2012

General principles of metabolism

Metabolic processes are highly controlled. Anabolism and catabolism are not necessarily balanced - one or the other may predominate in certain cells or at different times depending on needs. Pathway to synthesize a complex substance is not the reverse of the degradative pathway.

General principles of metabolism

Modes of control
(a) Level of energy if low, anabolism is unlikely/impossible. (b) Level of substrates (c) Level of enzyme cofactors (d) pH (e) Enzymes (f) Compartmentalize (g) Hormone control

Dr. Tey lai Hock

Dr. Tey lai Hock

Modes of control
Michaelis-Menten curve
v0 = Vmax[S] / (KM + [S]) Where v0 = initial velocity Vmax = max velocity [S] = substrate concentration KM = Michaelis constant

Modes of control
Levels of substrates and enzyme cofactors

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Dr. Tey lai Hock

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3/22/2012

Modes of control
pH

Modes of control
Enzyme concentration
(i) Quantity repression or induction of expression of information in DNA. (ii) Activity May have inactive or less active states, allosteric enzymes have +/- effectors, feedback control-build-up of product inhibits enzyme.

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Dr. Tey lai Hock

Modes of control
Activity Allosteric regulation & enzymes
Allos Other; stereo = solid (Translate from Greek) Allosteric regulation = regulation of an enzyme/protein by binding and an effector molecule at the protein allosteric site.
Inhibition

Modes of control
Allosteric regulation
Effectors can serve as stimulants/activators to the enzyme (positive effectors) or inhibitors of the enzyme (negative effectors). For example; a high concentration of A and low concentration of P, are signals that the metabolic sequence should proceed with the production of P. In this case, A may serve as a positive effector and substrate. When the product P reaches a certain desired level, it can serve as an inhibitor (negative effector).

Activation
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Modes of control

Modes of control
Compartmentalize
Some enzymes and substrates restricted to certain organelles so as to make the substrate available to enzyme in right place. For example, sphingolipids (SLs) metabolism pathway. SLs were considered to play primarily structural roles in membrane formation. Member of SL family, including ceramide (Cer), sphingosine (Sph), Sph-1-phosphate (C1P), as bioactive molecules playing roles from regulation of signal transduction pathways.

Dr. Tey lai Hock

Dr. Tey lai Hock

Modes of control
Compartmentalize

Modes of control
Hormone control
Hormones is the signaling molecules which synthesized and secreted by endocrine glands and transported to their site of action via the bloodstream. For example, insulin and glucagon hormones in controlling of blood glucose levels (pancreas).

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3/22/2012

Modes of control
Hormone control
Blood glucose level must be maintained within a rather narrow range. Resting individual = blood glucose concentration average 4.5 mM (~80 mg/100 ml). After a meal of carbohydrate (90g), protein (30g), and fat (20g) = 6-7 mM (100-125 mg/100 ml). After moderate exercise = 3.5 mM (60 mg/100 ml). Even after few weeks of starvation, blood glucose levels do not drop below 3 mM range.
Dr. Tey lai Hock

Modes of control

!!Thank you!!

Dr. Tey lai Hock

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