Bioenergetics and Metabolism - Lectures Prior to M1

Bioenergetics and Metabolism

• Metabolism involves coordinated cellular activity using multienzyme systems, also known as metabolic pathways.
• The four key functions of metabolic pathways:
  • Obtaining chemical energy from solar radiation or nutrients in the environment.
  • Converting nutrient molecules into unique cellular molecules, which serve as precursors to macromolecules.
  • Polymerizing monomeric precursors into macromolecules such as proteins, nucleic acids, and polysaccharides.
  • Synthesizing and degrading biomolecules with cellular function such as lipids, and messenger molecules.
• There are two primary classifications of organisms:
  • Autotrophs, encompassing photosynthetic bacteria, green algae, and vascular plants, that utilize carbon dioxide from the atmosphere and are self-sustaining.
  • Heterotrophs obtain carbon from organic molecules in the environment.

Anabolism Vs Catabolism

• Catabolism is the degradative process where organic nutrient molecules including carbs, fats, and proteins convert into smaller, simpler products.
  • Examples include lactic acid, water, carbon dioxide, and ammonia.
  • Energy is released in the form of ATP, and reduced electron carriers.
• Anabolism is the biosynthetic process where small precursors convert to larger molecules.
  • Examples include lipids, polysaccharides, proteins, and nucleic acids.
  • This process requires ATP phosphoryl transfer and reducing power of electron carriers.
• It is important to note that metabolic pathways can be linear or cyclic.
• Most cells have the enzymes to carry out both the degradation and synthesis of biomolecules like fatty acids.
• Anabolic and catabolic processes are irreversible and occur in different cellular locations.
• Enzymes operate at different tiers, and enzyme levels and metabolic intermediates regulated by internal, or external factors.
• Intracellular concentration of enzyme’s substrate is nearly always near the Km.
• Cellular activities are subject to metabolic regulation with allosteric regulation by a metabolic intermediate or coenzyme and by growth factors.

Bioenergetics and Thermodynamics

• Bioenergetics is the quantitative study of energy transductions, describing energy changes and the function of chemical processes.
• Notably, living cells and organisms operate as open systems, exchanging energy and material.
• Unlike closed systems nearing equilibrium, living systems sustain themselves by remaining out of equilibrium with the surroundings.
• Gibbs free energy (G) indicates the amount of energy available to do work during a reaction at a constant pressure and temperature.
  • Reactions can be exergonic (spontaneous) or endergonic (non-spontaneous).
• Enthalpy (H) measures the heat content of a reacting system and is determined by the number and kinds of chemical bonds in the reactants and products.
  • The reaction is exothermic if heat releases, resulting in products having lower heat content than reactants or are endothermic (endogonic) if it draws in heat.
• Entropy (S) quantifies the degree of randomness or disorder in a system, with products often being less complex, more disordered, and having lower complex entropy than reactants.
• Gibbs free-energy change (ΔG) is the change in enthalpy less the product of the change in the temperature and entropy, which influences the likelihood of the reaction taking place.
• Under standard conditions, cells maintain a consistent temperature.
• Heterotopic cells derive energy from nutrients, while photosynthetic capture solar radiation.
• A reacting system will change until equilibrium has been reached.
  • At this point the forward and reverse change are equal, and the constant of this equal exchange defines the equilibrium constant.
• The measurement of standard conditions are at temperature 298K, 1M concentrations, and partial pressures set at 1 atm.
• Standard free energy (ΔG’o) is the driving force to maintain balance.
• Relating the change to equilibrium constant is fairly straight forward.
• ΔG’o = -RTlnK’eq*
• Difference In free-energy content under standard conditions means the products have less of it than the reactants, allowing the process to take place; Negative values indicate spontaneity.
• Conversely, a positive standard free-energy change means products contain more energy than reactants, meaning that the process will proceed the other way.

Biochemical Reactions

• Actual free energy (ΔG) indicates reactant and product concentrations.
• Actual free energy is temperature sensitive.
• Reactions spontaneously approach a point of balance, and proceed when free energy tends towards negative.
• The standard free-energy, designated ΔG'o, remains constant.
• The process of equilibrium is constant, and unchanges from a point of reaction described using the equation:
  • ΔG = ΔG'o + RT ln([C]c[D]d/[A]a[B]b).
• Many reactions can proceed even if ΔG is recorded as being positive.

Reaction Types

• All cellular metabolism follows a set of reaction types and principles.
• Metabolism relies on five principal classes of chemical pathways:
  • Reactions breaking any compounds of carbon-carbon are a class of metabolism.
  • Isomerization or elimination of one or more part leads to a chemical alteration that is used for a cellular purpose for the body.
  • Radical, and group-transfer
  • and Oxidation-reduction based transformations are critical to bioenergetics.
• Covalent Bonds, made by sharing electrons, can cleave in two ways:
  • Where Homolytic cleavage atoms give off radicals
  • Where heterolytic cleavage is when an atom retains both electrons
• The nucleophiles will readily donate, while electrophiles are prone to accept them.
• Carbons take place as both electrophiles and nucleophiles!

Carbon bond formation

• Formation is based mostly on nucleophilic carbanion and electrophilic carbocation as the intermediates are unstable.
• Facilitated processes are achieved by the utilization of carbonyl, and Imine groups.

Isomerization

• Intramolecular rearrangements occur via alteration in molecule, and a product without oxidation occurs.
• Molecules that are going through red-ox reactions are always without oxidation
• The Cis/Trans transposition of double bonds causes some molecules to undergo reduction or oxidation, while others maintain the same status.

Free Radicals

• Homolytic cleavage of covalent bonds is extremely common for radicals.

• Isomerization of adenosylcobalamin, decarboxylation, reductase and Rearrangement can all have various byproducts.

Group Transfer Reactions

• Substrate-Enzyme interactions with a specific configuration for the interaction are referred to as phosphoryl groups.
• Attachment of a good leaving group to the metabolic intermediate is a great way to activate an intermediate for the process.

Oxidation-Reduction reactions

• Oxidation and Reduction Reactions are typically observed with Carbon where it can have 5 possible points of oxidation

• Oxidation and reductions occur for all major biochemical fuels with each step dependent upon whether oxidation results in bonding or not.

ATP

• ATP hydrolysis consists of resonance structures, meaning that it consists of three repeating groups of oxygen coordinated around a phosphorus with a negatively charged oxygen bridging that to the next group.
• The ATP4 hydrolysis also comes with liberation of charge repulsion.

Calculating ΔG

• There are many factors that influence an enzymes' ability to synthesize and breakdown ATP including the current conditions it experiences.

Group Transfers

• High or low phosphoryl transport, location etc all dictate how group transfer takes place when it comes to creating the high energy phosphate.

Donation

• Reaction generally follows SN1 and SN2 pathways.
• Alpha sites are most reactive

Nucleic acid energy requirements

• Simple precursors are assembled for polymers using specific weights and sequences.
• Condensation of monomeric units creates ordered consequences.
• The building blocked are nucleosides triphosphates with alpha and beta connections between these phosphates that get polymerized and releasing PPi.

Firefly flashes

• Bioluminescence, an energy consuming process that uses enzymatic action to create light.
• Light activation requires the cleavage of ATP and forms as luciferase comes into the composition.

Biological membranes

• The membranes create a cell by separating components within, and having the properties of a solution.
• Membranes help regulate molecular movement and traffic in the body while creating zones for reactions to occur, to maintain the energy balance needed for intercellular communication.
• The membranes are flexible but allow for selectivity between polar solutes.
• Transporters, receptors, and adhesion molecules for cellular processes are held here.
• Biological membranes exist as 2D crystalline liquids.

Biological Architecture and lipid fingerprints

• Proteins, lipids, and carbohydrates are in the composition including glyco units
• Each kingdom, cellular type, has a specific lipid composition in each cell’s organelles.
• Some proteins are linked covalently to oligo saccharides that have 60% mass.
• Glycoproteins can also have a role! They determine cell stability, fold proteins, and set a cell’s destination.

Biological properties

• Permeability is important as most membranes are impermeable to polar solutes.
• Functionality is important; it needs its asymmetrical arrangement of molecules and proteins to be proper.

Molecular Arrangement

• Micelles are spherical that use dozens of lipids.
• Bilayers are monolayers that create 2d sheets, often folded as they're unstable.
• Vesicles are surfaces that cover or remove hydrophobic or chemical ends.

Proteins in membranes

• Peripheral proteins can come and go with electrical charges.
• Inner membrane proteins are hard to remove.

Structural Motifs

• The most common structural point of protein is the αelix.

Lipid dynamics, composition, and transmembrane movement

• The dynamic membrane system needs to bend and move for body functions.

• Bacteria sense and create “on the go”

• Lateral and transmembrane movement allows for the distribution of lipids between leaflets.

• Phospholipids and other polar groups cannot penetrate layers.

Rafts and proteins

• Rafts include several points or proteins that can work on a timescale of seconds for efficient production.

Curvature and membrane fusion

• Curvature in membranes allows the body to perform at cellular levels.
• The process is assisted by fusion so that lipid layers, can come together