Notes 

CHAPTER 6

*Read about the history of aspirin.

Enzymes – proteins that act as critical catalysts to speed up thousands of different reactions in cells

Chemical reaction – a process in which one or more substances are changed into other substances

-Two generalized factors influence chemical reactions in living organisms: Rate and direction

-Generalized chemical equation

   aA+bB ßàcC+dD

-Chemical reactions:

A)      Form larger molecules

B)      Break apart to form smaller molecules

C)      Rearrange atoms within molecules

D)      Transfer electrons from one to another

Metabolism – the sum total of all chemical reactions that occur within an organism

-This may refer to cellular level. Ex) Fat metabolism

Energy – the ability to promote change or do work

Kinetic energy – energy associated with movement

Potential energy – the energy that a substance possesses due to its structure or location

Chemical energy – the energy contained within covalent bonds in molecules

Thermodynamics – the study of energy interconversions

-First Law of Thermodynamics – Energy cannot be created or destroyed, only changed (Law of conservation of energy)

-Second Law of Thermodynamics – The transfer of energy or transformation of energy increases entropy.

Entropy – a measure of the randomness of molecules in a system (degree of disorder)

-As energy becomes more evenly distributed, the energy is less able to do work or promote change

-heat may be released

-talk about latent heat of evaporation

Enthalpy – the total energy

-Total Energy=usable + unusable energy

-unusable energy – can be used to promote change or do work. ∆G=∆H - T∆S

Free energy (Gibbs free energy) – the amount of available energy that can be used to promote change or do work

Exergonic – a spontaneous reaction with a negative free-energy change

-A spontaneous reaction can be fast or slow

Endergonic – a non spontaneous reaction with a positive free-energy change

Adenosine triphosphate(ATP) – a molecule that is a common energy source for all cells

ATP à ADP + Pi  (Hydrolysis of ATP) -7.3 Kcal/mol (Energy Released)

Chemical equilibrium – the rate of formation of products equals the rate of formation of reactants

K equation

-When determineing equilibrium, scientists make two assumptions (1) water concentration does NOT change (2) pH stays neutral (The pH that is common for that environment.)

   aA+bB ßàcC+dD         Keq=[C]c [D]d

                                                             [A]a [B]b

Phosphorylation – the process where a phosphate is directly transferred from ATP to glucose

-Living organisms couple exergonic reactions with endergonic reactions.

-Glucose + Phosphate2- à Glucose – 6 - Phosphate2- + H2O ∆G= 3.3Kcal/mol

-ATP4- + H2O à ADP2- + Pi2-  ∆G= -7.3Kcal/mol

-Glucose + ATP4- à Glucose – 6 - Phosphate2- + ADP2- ∆G= -4.0Kcal/mol

(Hess’s Law or Heat summation)

-In order for a reaction to occur between glucose and ATP, the molecules must collide in the correct  orientation and possess enough energy so the chemical bonds can change.

Catalyst – an agent that speeds up the rate of a chemical reaction without being permanently changed or consumed.

Activation Energy – An initial input of energy in a chemical reaction that allows the molecules to get close enough to cause a rearrangement of bonds

-Must be greater than the electron cloud repulsion

-Adding heat can speed up reaction by providing more energy. Enzymes lower activation energy.

-Enzymes work by the following methods:

1) Enzymes work by bonding to the reactants which puts strain on the bonds, thereby making it easier for them to achieve transition state.

2) Enzymes also provide a site for the reactants to properly orientate to react.

3) Enzymes may change the local environment.

    Example in Figure 5.25

Transition State – In a chemical reaction, a state in which the original bonds have stretched to their limit; once this state is reached, the reaction can proceed to the formation of products

Active Site – The location in an enzyme where a chemical reaction takes place

Substrates – 1. The reactant molecules and/or ions that bind to an enzyme at the active site and participate in a chemical reaction. 2. The organic compounds such as soil or rotting wood that fungi use as food

Enzyme-Substrate Complex – The binding between an enzyme and its substrate

Specificity – Refers to the concept that enzymes recognize specific substates (Lock and key)

-Proposed by Emil Fischer in 1894

Ex. Hexokinase recognizes glucose, but not fructose and galactose.

Induced Fit – Occurs when a substrate binds to an enzyme and the enzyme undergoes a conformational change that causes the substrate to bind more tightly to the enzyme.

-Proposed by Daniel Koshland in 1958

Affinity – The degree of attraction between an enzyme and its substrate

-Enzyme – catalyzed reaction:

 Step 1) Building or release of substrate.

Step 2) Formation of product

E+SßàESßà E+P

E= enzyme  S=substrate  ES=enzymes substrate complex  P=product

Vmax – The maximal velocity of an enzyme-catalyzed reaction.

KM – The substrate concentration at which an enzyme-catalyzed reaction is half of its maximal value

-Inversely related to affinity

Competitive Inhibitors – A molecule that binds to the active site of an enzyme and inhibits the ability of the substrate to bind

-These are molecules that generally have structures similar to the enzymes substrates which allow them to bind to the enzyme

-Higher KM is needed for the reaction rate top stay the same.

Noncompetitive Inhibitor – A molecule that binds to an enzyme at a location that is outside the active site and inhibits the enzyme’s function

Allosteric Site – A site on an enzyme where a molecule can bind noncovalently and affect the function of the active site

Prosthetic Groups – Small molecules that are permanently attached to the surface of an enzyme and aid in catalysis

-Generally nonproteins or ions

Cofactors – Usually an inorganic ion that temporarily binds to the surface of an enzyme and promotes a chemical reaction

-usually Fe+3 or Zn+2

Coenzymes – An organic molecule that participates in a chemical reaction with an enzyme but is left unchanged after the reaction is completed

-They can be synthesized by cells, but generally are takin in as dietary vitamins

Ribonucleoprotein – A complex between an RNA molecule and a protein

Ribozyme – A biological catalyst that is an RNA molecule

*6.3 Overview of Metabolism*

Metabolic pathways – In living cells, a series of chemical reactions in which each step is catalyzed by a specific enzyme

Catabolic Reactions – A metabolic pathway in which a molecule is broken down into smaller components, usually releasing energy (exergonic reaction)

-Nucleases – enzymes that break RNA into nucleotides and release energy.

-Proteases – enzymes that break proteins into amino acids and release energy.

Anabolic reactions – A metabolic pathway that involves the synthesis of larger molecules from smaller precursor molecules. (Endergonic reaction)

-Such reactions usually require an input of energy

-These reactions must be compelled with an exergonic reaction

Energy Intermediates – A molecule such as ATP or NADH that stores energy and is used to drive endergonic reactions in cells

-p.129 Phosphoenolpyruvate + ADP à Pyruvate + ATP  ∆G= -7.5 Kcal/mole

*This is complete in a series of steps called glycolysis* (opposite of what)

Substrate-Level Phosphorylation – A method of synthesizing ATP that occurs when an enzyme directly transfers a phosphate from an organic molecule to ADP

Chemiosmosis – A process for making ATP in which energy stored in an ion electrochemical gradient is used to make ATP from ADP and Pi

Oxidation – A process that involves the removal of one or more electrons; occurs during the breakdown of small organic molecules

-It is called oxidation because Oxygen is typically involved in the removal of the electron from the other molecule

Reduction – A process that involves the addition of electrons to an atom or molecule

-Named because the addition of electrons reduces the charge of the molecule.

Redox Reaction – A type of reaction in which an electron that is removed during the oxidation of an atom or molecule is transferred to another atom or molecule, which becomes reduced; short for a reduction-oxidation reaction

-They occur together because of free electrons do NOT exist in solutions

NAD+ - Nicotinamide adenine dinucleotide; a dinucleotide that functions as an energy intermediate molecule. It combines with two electrons and H+ to form NADH

-NADH is used to make ATP or is used to energize other molecules

Biosynthetic Reactions – Also called an anabolic reaction. A chemical reaction in which small molecules are used to synthesize larger molecules (described in chapter 12)

-copy equation on p.129

Genomes and Protenomes connection

-A typical cell uses millions of ATP molecules/second

-An average person hydrolyzes about 100 pounds of ATP/day

-Each ATP undergoes about 10,000 cycles of hydrolysis and resynthesizes during an ordinary day

Proteomes – all of the proteins that make up a given cell.

-over 20% of all proteins bind ATP

Metabolic Pathways are regulated in three general ways

-catabolic reactions normally occur when a molecule is no longer needed or energy is needed in the cell

-anabolic reactions normally occur only when new macromolecules are needed.

1) Gene regulation – Genes regulate the production of enzymes

Ex. If a certain sugar is NOT in a cell, the cell stops producing the enzyme to break it down.

2) Cellular Regulation – cells integrate signals from their environment and adjust their chemical reactions to adapt to those signals (Chapter 9)

Ex. When people are frightened, epinephrine is released into their bloodstream. Epinephrine binds to the surface of muscle cells (p.131) Add more?

3) Biochemical regulation – the binding of an enzyme or biomolecule directly regulate its function.

Ex. Production of competitive or noncompetitive inhibitors.

Feedback Inhibition – A from or regulation in which the product of a metabolic pathway inhibits an enzyme that acts early in the pathway, thus preventing the over accumulation of the product. (p.132 fig 6.13)

Rate-Limiting Step – The slowest step in a pathway

-This step is the one that is controlled, because it controls all other steps.

*6.4 Recycling Macromolecules*

Half-Life – 1. In the case of organic molecules in a cell, refers to the time it takes for 50% or the molecules to be broken down and recycled. 2. In the case of radioisotopes, the time it takes for 50% of the molecules to decay and emit radiation

-DNA is basically the only macromolecule which is stable.

-mRNA has a half-life of five minutes in prokaryotes, but 30 minutes to several days in eukaryotes

Recycling macromolecules allows cells to be efficient with regards to energy and waste. It also allows cells to quickly and efficiently respond to their environment.

Degradation of mRNA has two important factors:

1)      Some mRNA is only needed in certain situations

2)      Some mRNA may be faulty

In most cases, degradation begins with the removal of nucleotides in the poly A tail at the 3’ end. Once the poly A tail is removed, two mechanisms are possible:

A)      Remove the 5’ cap and remove 1 nucleotide at a time from that end.

B)      The Exosome continues along the mRNA from the 3’ tail (p. 133)

Exonuclease – An enzyme that cleaves off nucleotides, one at a time, from the end of a DNA or RNA molecule

Exosome – A multiprotein complex that degrades mRNA

Protease – An enzyme that cuts proteins into smaller polypeptides

Proteasome – A molecular machine that is the primary pathway for protein degradation in archaea and eukaryotic cells

-The core is formed by four stacked rings each made of 7 proteins. Each end is capped with 30 proteins. (p. 134)

Ubiquitin – A small protein in eukaryotic cells that directs unwanted proteins to a proteasome by its covalent attachment

-They recognize improperly folded proteins.

Step of protein degradation:

1)      Ubiquitin proteins are attached to target proteins.

-The protesome cap has a binding site for the proteins.

A) Enzymes in the cap unfold the protein

B) The protein is injected into the internal cavity of the proteasome core.

C) Ubiquitin proteins are removed and returned to the cytosol.

2)    Inside the proteasome, proteases degrade proteins into small peptides and amino acids which are recycled in the cytosol.

-This rapid protein breakdown is needed during several steps of cell division

Autophagy – A process whereby cellular material, such as a worn-out organelle, becomes enclosed in a double membrane and is degraded

-Chapter 4 discussed that lysosomes break down proteins, carbohydrates, nucleic acids, and lipids. (worn out organelles)

-Chapter 5 discussed how enzymatic functions allow lysosomes to break down materials after endocytosis.

-steps to Autophagy on p. 134

Autophagosome –  A double-membrane structure enclosing cellular material destined to be degraded. Produced by the process of autophagy