Midterm Flashcards
Metabolism
- 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)
Functions of Metabolism
- 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
Energy is Required to Meet Three Fundamental Needs
- 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
Basic Principles Govern Energy Manipulation in all Cells
- 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
Metabolic Pathways
- 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
Linear Metabolic Pathways
- 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)
In order to construct a metabolic pathway, two criteria must be met:
- 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)
Branched Metabolic Pathways
- Linear path with multiple ends
- Too much of one can become an allosteric inhibitor for another
(Lesson 1, Slide 10)
Circular Metabolic Pathways
i.e. The Citric Acid Cycle
Metabolism is Composed of Many Interconnecting Reactions
- 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
Metabolic Pathways can be divided into two types
- 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
Principles of Bioenergetics
- Transformation and use of energy by living cells
Thermodynamic Laws
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
Free Energy (G)
- 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 °’
Heat Energy (H)
- Total heat content (energy) of a system referred as enthalpy occurs through a change of temperature and pressure
Entropy (S)
- Energy in a state of randomness and disorder (useless energy)
Relationship between the different energy terms
△G = △H - T△S
- T is the absolute temperature on Kelvin scale (273 + C°)
Free Energy Change and Chemical Reactions
△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)
Standard Free Energy Changes are Additive
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
Actual Free Energy
- 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)
ATP is The Universal Currency of Free Energy
- Energy derived from fuels or light is converted into adenosine triphosphate (ATP), the cellular energy currency
ATP Hydrolysis is Exergonic
- 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
ATP has a high phosphoryl-transfer potential because of three key factors
- Charge repulsion
- Resonance stabilization
- Stabilization by hydration
Biological Oxidation and Reduction Reactions
- 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)
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)
Flavin Adenine Dinucleotide (FAD)
- Picks up 2 electrons and 2 H(+)
- Loses a double bond
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)
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:
- Amounts of Enzymes (more energy, makes)
- Make more or less, and degrade
- Transcription regulation
- Translation regulation - Enzyme Catalytic Activity (less energy, maintain)
- Inhibitors and Activators (pathways, allosteric event)
- Covalent modification - hormones (phosphorylation) - Accessibility of Substrates (compartmentalization)
- Electron can’t find substrate
- Amounts of Enzymes (more energy, makes)
The Capturing of Energy from Food Occurs in Three Stages:
- Large molecules in food are broken down into smaller molecules in the process of digestion (lipids -> fatty acids, proteins -> amino acids, and polysaccharides -> glucose)
- The many small molecules are processed into key molecules of metabolism, most notable acetyl CoA (fatty acids, amino acids, glucose)
- ATP is produced from the complete oxidation of the acetyl component of acetyl CoA
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
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
Glycolysis Can Be Divided into Two Parts
- Glycolysis can be thought of as occurring in two stages:
- Stage 1 traps glucose in the cell and modifies it so that it can be cleaved into a pair of phosphorylated 3-carbon compounds
- Stage 2 oxidizes the 3-carbon compounds to pyruvate while generating two molecules of ATP
Hexokinase Reaction
- Glucose + ATP –> Glucose 6-phosphate + ADP + H(+)
- Hexokinase reaction (–>)
- Hexokinase traps glucose in the cell and begins glycolysis
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)
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
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
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
Aldolase Reaction
- Fructose 1,6-biphospahte (F-1,6-BP) –> Dihydroxyacetone phosphate (DHAP)
