1
Q
Metabolism
A
- Refers to enzyme catalyzed reactions collectively
- It is highly coordinated and provides purposeful cell activity in which many multienzyme systems cooperate
- It is the sum of anabolism and catabolism
- Anabolism = biosynthetic reactions, small simple molecules are converted into larger and more complex molecules (require energy)
- Catabolism = breakdown or degradation reactions, organic nutrient molecules are converted into smaller simpler molecules (produce energy)
2
Q
Functions of Metabolism
A
- To obtain chemical energy from the degradation of energy-rich nutrients from the environment or from captured solar energy
- To convert nutrient molecules into building blocks of cell macromolecules
- To assemble these building blocks into macromolecules (proteins, nucleic acids, lipids, polysaccharides)
- To form and degrade biomolecules required in specialized functions of cells
3
Q
Energy is Required to Meet Three Fundamental Needs
A
- Energy is required to power muscle contractions, cell movement, and biosynthesis
- Phototrophs obtain energy by capturing sunlight
- Chemotrophs obtain energy through the oxidation of carbon fuels
4
Q
Basic Principles Govern Energy Manipulation in all Cells
A
- Molecules are degraded or synthesized stepwise in a series of reactions termed metabolic pathways
- ATP is the energy currency of life
- ATP can be formed by the oxidation of carbon fuels (most oxidized is CO2)
- A limited number of reaction types that involve particular intermediates are common to all metabolic pathways
- Metabolic pathways are highly regulated (building and degrading)
- The enzymes involved in metabolism are organized into large complexes
5
Q
Metabolic Pathways
A
- Term is used for a sequence of reactions
- They could be Linear, Branched, or Circular
- Reactions could be reversible or irreversible, regulated and usually the first reaction catalyzes a committed step
- The intermediates in a metabolic pathway are referred as metabolites
- Reactants and Products are referred as Substrates and Products
6
Q
Linear Metabolic Pathways
A
- Reactions could be reversible or irreversible
- Usually, the first reaction of a metabolic pathway is irreversible, Regulates and catalyzes a committed step
(Lesson 1, Slide 7)
7
Q
In order to construct a metabolic pathway, two criteria must be met:
A
- The individual reaction must be specific
- The pathway in total must be thermodynamically favourable
- A thermodynamically unfavourable reaction in a pathway can be driven by coupling to a more favourable reaction (loop-de-loop roller coaster)
8
Q
Branched Metabolic Pathways
A
- Linear path with multiple ends
- Too much of one can become an allosteric inhibitor for another
(Lesson 1, Slide 10)
9
Q
Circular Metabolic Pathways
A
i.e. The Citric Acid Cycle
10
Q
Metabolism is Composed of Many Interconnecting Reactions
A
- Metabolism is a series of linked reactions that convert a specific reactant into a specific product
- The entire set of cellular metabolic reactions are called intermediary metabolism
11
Q
Metabolic Pathways can be divided into two types
A
- Catabolic pathways combust carbon fuels to synthesize ATP
- Anabolic pathways use ATP and reducing power to synthesize large biomolecules
- Amphibolic pathways, can function anabolically or catabolically
- Although anabolic and catabolic pathways may have reactions in common, the regulated, irreversible reactions are always distinct
12
Q
Principles of Bioenergetics
A
- Transformation and use of energy by living cells
13
Q
Thermodynamic Laws
A
First Law: in any physical or chemical change the total amount of energy in the universe remains constant
Second Law: the amount of entropy (total disorder) in the environment increases as a result of all chemical or physical changes
14
Q
Free Energy (G)
A
- The kind of energy that performs useful work at constant temperature and pressure
- If △G is negative, the reaction is exergonic (initial G is higher than final G)
- If △G is positive, the reaction is endergonic (initial G is lower than the final G)
- Standard free eneregy chamge (at 1M initial concentration and 1 amp) at pH 7.0 is written delta △G °’
15
Q
Heat Energy (H)
A
- Total heat content (energy) of a system referred as enthalpy occurs through a change of temperature and pressure
16
Q
Entropy (S)
A
- Energy in a state of randomness and disorder (useless energy)
17
Q
Relationship between the different energy terms
A
△G = △H - T△S
- T is the absolute temperature on Kelvin scale (273 + C°)
18
Q
Free Energy Change and Chemical Reactions
A
△G°’ = -RTln(Keq)
- △G°’ is the standard free energy change
- R is the Gas constant (8.315 J/mol)
- T is the Kelvin temperature (273 + C°)
- ln is 2.3 log
- Keq is the equilibrium constant
This reaction can also be written as: △G°’ = 2.3 RT log (Keq)
- △G Free Energy Change
- △G° Standard Free Energy Change at 1M initial concentration [ ] and 1 atm pressure 101.3 Kpa
- △G°’ Standard Free Energy Change at pH 7.0
- K’eq = 1 (△G°’ = 0 reaction at equilibrium)
- K’eq < 1 (△G°’ = +, favours reverse reaction)
- K’eq > 1 (△G°’ = -, favours forward reaction/ spontaneous reaction)
19
Q
Standard Free Energy Changes are Additive
A
Reaction 1: △G1°’ = 13.8 kJ/mol (not spontaneous)
Reaction 2: △G2°’ = -30.5 kJ/mol (spontaneous)
Overall △G°’ = △G1°’ + △G2°’ = -16.7 kJ/mol
- A thermodynamically unfavourable reaction in a pathway can be made to occur by coupling it to a more favourable reaction
20
Q
Actual Free Energy
A
- For the reaction: A + B = C + D
- The free energy change is given by: △G = △G° + RT ln (CD)/(AB)
(Lesson 2, slide 8 + 10)
21
Q
ATP is The Universal Currency of Free Energy
A
- Energy derived from fuels or light is converted into adenosine triphosphate (ATP), the cellular energy currency
22
Q
ATP Hydrolysis is Exergonic
A
- The hydrolysis of ATP is exergonic because the triphosphate unit contains two phosphoanyhydride bonds that are unstable
- The energy released on ATP hydrolysis is used to power a host of cellular functions
23
Q
ATP has a high phosphoryl-transfer potential because of three key factors
A
- Charge repulsion
- Resonance stabilization
- Stabilization by hydration
24
Q
Biological Oxidation and Reduction Reactions
A
- Oxidation: loss of electron(s), and sometimes also proton(s)
AH2 –> A + 2H(+) + 2e(-) - Reduction: Gain of electron(s) and sometimes also proton(s)
B + 2H(+) + 2e(-) –> BH2 - Overall reaction is: AH2 + B –> A +BH2
- Reduction Potential (E): measures affinity for electrons, unitin volts
- Standard reduction potential, E°
- Standard reduction potential at pH 7.0, E°’
- Electrons moves from lower E° to higher E°
- H(+) + e(-) = 1/2 H2 E° = 0 [+ = high affinity for e(-) and - = low affinity for e(-)]
- Net potential calculation:
E°’ net = E°’ (for reduction reaction) - E°’ (for oxidation reaction)
25
Nicotinamide Adenine Dinucleotide (NAD+)
- Picks up 2 electrons and a H(+)
- Loses a double bond
- Moves down energy cascade spontaneously (from not good electron acceptor to good electron acceptor)
26
Flavin Adenine Dinucleotide (FAD)
- Picks up 2 electrons and 2 H(+)
- Loses a double bond
27
Energetics of Electron Transfer
- △G°' = -nFE°' net
- n = number of electrons
- F = Faraday's number (96.5 kJ/volt/mol)
- E°' net = Net Reduction Potential
- If E°' net is positive, △G°' will be negative (means a spontaneous reaction and exergonic)
- Net Reduction potential is:
E°' net = E°' (for reduction reaction) - E°' (for oxidation reaction)
(Lesson 3, slides 8-10 examples)
28
Regulation of Metabolic Processes: Three Principal Ways
- Homeostasis, a stable biochemical environment, is maintained by careful regulation of biochemical processes.
- Three regulatory controls are especially prominent:
1. Amounts of Enzymes (more energy, makes)
- Make more or less, and degrade
- Transcription regulation
- Translation regulation
2. Enzyme Catalytic Activity (less energy, maintain)
- Inhibitors and Activators (pathways, allosteric event)
- Covalent modification - hormones (phosphorylation)
3. Accessibility of Substrates (compartmentalization)
- Electron can't find substrate
29
The Capturing of Energy from Food Occurs in Three Stages:
1. Large molecules in food are broken down into smaller molecules in the process of digestion (lipids -> fatty acids, proteins -> amino acids, and polysaccharides -> glucose)
2. The many small molecules are processed into key molecules of metabolism, most notable acetyl CoA (fatty acids, amino acids, glucose)
3. ATP is produced from the complete oxidation of the acetyl component of acetyl CoA
30
Digestion of Dietary Carbohydrates
- Starch, Glycogen are degraded to glucos, maltose and oligosaccharides by salivary and pancreatic amylases
- In ruminants, cellulose is converted to glucose by cellulase
- In small intestine
- Lactose (milk sugar) is converted to glucose and galactose by lactase (β-galactosidase)
- Sucrose (common sugar) is converted to glucose and fructose by sucrase (invertase)
- Maltose is converted to glucose by maltase
- Galactose and Fructose can be further converted to glucose
- Monosaccharides are the transported into the cells and subsequently into the bloodstream
31
Family of Glucose Transporters
- Name: Tissue Location; KM; Comments
- GLUT1: all mammalian tissues; 1mM; basal glucose uptake
- GLUT2: liver and pancreatic β cells; 15-20 mM; in the pancreas, plays a role in the regulation of insulin, in the liver it removes excess glucose from the blood
- GLUT3: all mammalian tissues; 1 mM; basal glucose uptake
- GLUT4: muscle and fat cells; 5 mM; amount in muscle plasma membrane increase with endurance training
- GLUT5: small intestine; 15 mM; primarily a fructose transporter
- Higher amount of KM = handle more glucose
32
Glycolysis Can Be Divided into Two Parts
- Glycolysis can be thought of as occurring in two stages:
1. Stage 1 traps glucose in the cell and modifies it so that it can be cleaved into a pair of phosphorylated 3-carbon compounds
2. Stage 2 oxidizes the 3-carbon compounds to pyruvate while generating two molecules of ATP
33
Hexokinase Reaction
- Glucose + ATP --> Glucose 6-phosphate + ADP + H(+)
- Hexokinase reaction (-->)
- Hexokinase traps glucose in the cell and begins glycolysis
34
Hexokinase
- Hexokinases phosphorylates hexoses in various tissues
Muscle
- Enzyme: Hexokinase I
- Substrate (Glucose): non-specific (phosphorylates other sugars)
- Km (Glucose): 0.1 mM
- Inhibition by glucose 6-P: Yes (regulated by end product
Liver
- Enzyme: Glucokinase (Hexokinase iV)
- Substrate (Glucose): 5-10 mM
- Inhibition by Glucose 6-P: No (because liver processes glucose to glycogen, remove glucose from blood stream)
35
Isomerization of Glucose 6-phosphate (G6P) to Fructose 6-phosphate (F6P)
- Glucose 6-phosphate (G-6P) --> Glucose 6-phosphate (open-chain form) --> Fructose 6-phosphate (open chain form) --> Fructose 6-phosphate (F-6)
-The reaction is catalyzed by Phosphoglucose Isomerase
36
Generation of Fructose 1,6-biphosphate by Phosphofructokinase-1 (PFK-1)
- Fructose 6-phosphate (F-6P) + ATP --> Fructose 1,6-biphosphate (F-1,6-BP) + ADP + H(+)
- Phopshofructokinase reaction
- Bis- means two separate monophosphoryl groups are present
- Di- means two phosphoryl groups are present and are connected by an anhydride linkage
37
Allosteric Regulation of Phosphofructokinase-1 (PFK-1)
- Low [ATP] (makes product on low contentration)
- Greater reaction velocity per Fructose 6-phosphate
- High [ATP] (doesn't want to make because enough already)
- Lower reaction velocity per Fructose 6-phosphate
38
Aldolase Reaction
- Fructose 1,6-biphospahte (F-1,6-BP) --> Dihydroxyacetone phosphate (DHAP)
Bmsc 230
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