# Lecture 3 - Biochemistry **Overview:** 1. Chemical Bonds and Free Energy 2. Weak Bonds in Biological Systems 3. High Energy Bonds in Biological Systems 4. ATP “High Energy vs Low Energy Bonds” A high energy bond is unstable and wants to break down - *High Energy → Unstable → Weak Bond* - Higher bond energy → Shorter bond length - Can form and break (reversible) under physiological conditions, an essential feature otherwise biological components would freeze up - Weak bonds are longer than strong bonds (Van der Waals H-H = 1.2 angstroms) - Weak bonds have more variable bond angles A low energy bond is stable and does not want to change - *Low Energy → Stable → Strong Bond* - Strong covalent bonds are essential for biological macromolecules - Do not break down spontaneously Life evolved to rely on carbon as a skeletal atom within molecules likely because of its ability to form 4 consecutive bonds. Single covalent bonds (sigma bonds) allow free rotations - Meanwhile double and triple bonds are rigid - Bonds with partial double bond character are also rigid - therefore the C=O and N=C must lie within the same plane as they share resonance/partial bond characteristics D-Glucose = Dextrose Our bodies use L-form amino acids - Enzymes would not be able to bind properly to D-form amino acids even if they were present. - [ ] How capable are single bonds at supporting the weight/burden of covalently bonded macromolecules? - (Ex: single linker relies on a peptide bond for a fusion protein) --- **Chemical Bond Formation Involves a Change in the Form of Energy** - The *First Law of Thermodynamics* states that *energy can neither be created nor destroyed*. - This concept dictates the energy “storage” that is occuring within chemical bonds - It is also why the energy required to break a bond is exactly the same as the energy released during its formation $A+B \rightarrow AB + \text{Energy}$ - The stronger the bond, the greater the amount of energy released upon its formation, and thus the more energy needed to break it (due to first law of thermo?) - The rate of a reaction is directly proportional to the frequency of collisions between A and B (particles speed up as temperature increases → collisions increase as a result) $AB + \text{Energy} \rightarrow A+B $ - Heat can be a source of energy that can berak chemical bonds - As temperature for a system increases, the molecules begin the move faster and the stability of their bond increases (do they become more likely to collide with eachother?) - The notion that “chemical bonds store energy that is released when broken” is incorrect - It takes an input of energy to break a bond - The process rarely stops with just breaking bonds, - The question is, does the energy required to break the bonds outweigh the energy released by the subsequent bond formation ![[Pasted image 20240129160703.png|400]] - When two atoms are brought together to form a bond, they will form the *optimal distance* (known as the *bond length*) which balances their repulsive and attractive forces - Close enough where they are sharing electrons (covalent bonds) - Far enough apart to avoid overlapping - All contribution: all chemical bonds (weak or strong) are based on *electrostatic forces* --- **Chemical Equilibrium** - Every bond in a system is a result of the combined actions of bond making and bond breaking, both of which are constantly *moving towards an equilibrium* (Le Chatelier’s Principle) - Doesn’t mean a 50/50 concentration - When equilibrium is reached, the number of bonds forming per unit of time equals the number of bonds breaking --- **Chemical Thermodynamics** - $\Delta G$ is the energy available to do work (within a system) - It is a function of - Second Law of Thermodynamics: a chemical or physical process goes spontaneously in the direction of greater disorder (rise in $\Delta S$) - Enthalpy is the total heat content of a system (at constant pressure) - It often decreases in spontaneous reactions, meaning that heat is lost/released from the system - Entropy is a measure of “microstates”, specifically the multiplicity - A microstate refers to a specific arrangement or configuration of individual particles (atoms, molecules) in a system. It describes the microscopic state of the system - A macrostate is a description of the system in terms of macroscapic properties such as temperature, pressure, and volume. A macrostate can correspond to many different macrostates (the degree of which is represented by the multiplicity $\Omega$) - [ ] Why don’t systems have an infinite number of microstates? Hydrogen andd oxygen gases react spontaneously to form water - Yes, because the Gibbs free energy of the forward reaction is negative Standard Temperature and Pressure (STP) ### Monday, January 29th > Zoom Recording - $\Delta G \degree$ (biochemistry) 1 M, We can’t often use $\Delta G_{actual}$ because its extremely difficult to measure the exact concentrations within a cell at any given time, instead we rely on $\Delta G^{`}\degree$ $\Delta G_{actual} = \Delta G^{'}\degree + RT... $ Many biosynthetic pathways require an input of energy from high energy compounds - ATP, NADH, FADH, Acetyl-CoA Not all individual steps in biological pathways has to have a negative free energy change - If the overall pathway has a positive delta G, the reaction can still proceed forward (typically caused by concentration/Le Chateliers Principle) ![[Pasted image 20240129134403.png|300]] If chemical reactions didn’t have high activation energies acting as a barrier, all molecules would drift to their lowest energy forms over time (sugars in our bodies would break down on their own, before we have the opportunity to use them) - Enzymes lower the activation energy Hydrolysis (consuming a water to cleave a molecule) is often favorable --- **ATP** - AMP does not have a high energy bond (phosphoester) - ATP has two phosphoanhydrides - are weak bonds that want to break down - these two groups have *competing resonance* which can be relieved upon hydrolysis - In general, the hydrolysis of ATP drives cellular work by releasing energy that can be coupled to other reactions - ADP has greater entropy than ATP () - Disadvantage of ADP: The leaving group would be a phosphate → a massive concentration of phosphates would drive equilibrium backwards - While the hydrolysis of ATP by water is an extremely favorable reaction, the activation energy necessary is also quite high and serves as a kinetic barrier causing the reaction to occur at a very slow rate - This activation energy can be lowered through the use of enzymes, in fact, the vast majority reactions using ATP require this enzymatic aid **ATP Group Transfer** - Coupled reactions cannot be the result of two completely separate reactions - Two or more successive reactions can be coupled using a group transfer, aka the exchanging of functional groups (AMP or a phosphate) - High energy (unstable) intermediates make the substrate vulnerable to attack from other reactants --- ![[zjvzcfh_orig.gif|100]] there are several higher energy molecules capable of phosphorylating ATP: - phosphoenolpyruvate - 1,3-bisphosphoglycerate - phosphocreatine (muscles) It’s crucial to remember that regardless of a reaction’s $\Delta G$, it can still occur if its equilibrium is disturbed enough (drastically different concentrations of products vs reactants) --- **ATP and Protein Synthesis** - Protein synthesis is unfavorable and peptides can break down over time - ![[Pasted image 20240201074512.png|300]] - Formation of the peptide bond during protein synthesis results in the production of 1 water molecule --- **ATP and Protein Function** - Phosphorylation is crucial for *signal transduction* - many signaling pathways are regulated by *kinases* and *phosphorylases* (hot potato with phosphates) - Membrane Transport - ATP-binding cassette transporters - Sodium-potassium pump (sodium in & potassium out) - MacB ABC transporter (antibiotic and enterotoxin efflux in bacteria) ATP > [!question] Phosphate Concentrations > Because of how fundamental ATP is in mediating our cell’s reactions, and also because phosphates can… > - how reactive are free phosphates or biphosphates?