Chemistry 2, ,End of Year Exam

Carbohydrates, Lipids, Amino Acids, Proteins, Enzymes, Chemistry of Medicines, Nutrition, Nucleic acids, and Bioenergetics.

Name, Structure, and Three Letter Code for the Amino Acids You need to Know

Zwitterions

• Neutral solutions

• It is a dipolar ion made by a transfer of a proton from –COOH to –NH2 

• Overall charge is still zero

Calculate the pI for a neutral amino acid like glycine....which has two pKas : pK_COOH and pK_NH

Classes of Enzymes (Over The HILL)

Oxidoreductases

Enzyme that catalyse the oxidation-reduction reaction between the two substrates

Transferases

Enzymes that catalyse the transfer of functional group between two substrates

Hydrolases

Enzymes that catalyse the hydrolysis of esters, carbohydrates, and proteins (polypeptides)

Isomerases

Enzymes that catalyse the interconversion of stereoisomers and structural isomer

Lyases

Enzymes that catalyse the removal of groups from substrates by mechanisms other than hydrolysis

Ligases

Enzymes that catalyse the linking of two compounds by breaking a phosphate anhydride bond in adenosine triphosphate (ATP)

The energy necessary to move a reactant to the transition state is called the…?

…activation energy

(The larger this energy barrier is the slower the reaction rate will be)

Common Ways to increase a Reaction Rate

• Increasing the reactant concentration

• Increasing the reaction temp

• Adding a catalyst

What is Vmax?

So once we reach Vmax, it doesn't really matter HOW much more substrate we give it, the reaction cannot go any faster than it's already going.

This curve is called a hyperbolic curve

Protein-Ligand Binding

• A ligand is a molecule which produces a signal by binding to a site on a target protein

• The greater the intermolecular forces, the greater the binding affinity

• You need less concentration of a higher-affinity binding ligand, to maximally occupy a ligand-binding site, and trigger a response

More Selective Drugs

Drugs that are more selective are safer to use as they target the specific response in the body.

• There are two isoenzymes – COX-1 and COX-2

• The substrate binding channel of COX-1 is smaller than the binding channel of COX-2

• Flurbiprofen can fit into both binding channels, while SC-558 is larger than flurbiprofen and is unable to fit into the COX-1 binding channel

Intermolecular Forces

1. Dispersion forces

• weakest intermolecular force (0.5-1.0 kcal/mole)

• electrostatic

• occurs between nonpolar groups (e.g. hydrocarbons)

• highly distance and temperature dependent

2. Dipole-Dipole Bonding

• stronger (1.0 to 10 kcal/mole)

• occurs electrostatically between electron deficient and electron rich atoms (dipoles)

• hydrogen bonding is a specific example of this bonding and serves as a prime contributor to hydrophilicity

• Dipole results from an unequal sharing of the pair of electrons in a covalent bond.

• Found when the two covalently bonded atoms differ greatly in electronegativity

3. Hydrogen Bonding

• Stronger bond than van der Waal

• Less affected by temperature or distance

• Give hydrophilic character to chemical

• Accounts for water-solubilizing properties of organic compounds

4. Ionic Bonding

• electrostatic attraction between cations and anions

• common in inorganic compounds and salts of organic molecules

• relatively strong (5 kcal/mole)

5. Ion-Dipole Bonding

• electrostatic between a cation/anion and a dipole

• relatively strong (1-5 kcal/mole)

• low temperature and distance dependence

• important attraction between organic compounds and H₂O

• Electrostatic attraction that occurs between a formally charged ion and a dipole.

• If the salt can dissociate in water (i.e., separate), water solubility can occur.

• Can play a significant role in dissolving organic compounds in water

Oxidation, demethylation, and glucuronidation increases polarity and water solubility

Oxidation is the loss of electrons

Demethylation is the loss of a melthy group

Glucuronidation is the gain of a sugar group

HMG CoA Reductase Inhibitors

• HMG CoA reductase (HMG stands for 3-Hydroxy-3-MethylGlutaryl) is responsible for the conversion of HMG CoA to mevalonic acid 

• HMG CoA reductase inhibitors are also called "statins", or more correctly "vastatins"

• Mevastatin & lovastatin served as lead compounds for the development of alternative HMG Co reductase inhibitors

Monosaccharides

• Glucose

• Fructose

• Galactose

Disaccharides

• Maltose

• Sucrose

• Lactose

Polysaccharides

Starch

• storage form of glucose in plants 

• found in grains and legumes. 

• Amylose, Amylopectin 

Glycogen

• storage form of glucose in the body 

• provides a rapid release of energy when needed. 

Fibre

• provides structure in stems, trunks, leaves, roots etc. 

• generally not digestible 

• Soluble and insoluble

Epimer?

Enantiomer?

Diastereomer?

Anomers?

Epimer= differ on one chiral carbon

Enantiomer= mirror image

Diastereomer= differ on more than one chiral carbon (not all)

Anomers= two cyclic isomers that differ only in their stereo arrangement about the carbon involved in mutarotation.

Hemiacetal? Acetal?

Hemiacetal= ether and alcohol on the same carbon, meaning the molecule will undergo mutarotation

Acetal= two ethers on the same carbon, meaning the molecule will-not undergo mutarotation

The first carbon that is bonded to 2 oxygens is called the…?

…anomeric atom

Mutarotation

• When alpha and beta forms of glucose are put into separate solutions and allowed to stand, the rotation of polarized-light becomes the same

• This is called mutarotation

• During mutarotation the two cyclic forms come together through the open chain form

• Resulting in 36% being alpha, 64% being beta, and the rest in trace amounts

How are disaccharides are connect by…?

Disaccharides are connect by glycosidic linkages

Lipoproteins

Lipoproteins transport lipids through the bloodstream

 

• Chylomicrons: largest, but least dense. Reduce in size as triglycerides are removed. 

• VLDLs: Very low density lipoproteins. 

• LDL: Low density (‘Bad’) lipoproteins (to the body)

• HDL: High density (‘Good’) lipoproteins (to the liver)

Phospholipids

• Group of compounds that make one or more fatty acid molecules, phosphate group, and nitrogenous base after hydrolysis

• Have a hydrophilic end that interacts with water

Sphingolipids

Sphingomyelin are found in the myeline sheath membrane in nerves

Glycolipids

• Contain carbohydrate group

• With the two most important being cerebrosides and gangliosides

• These are found in cell membranes of nerve and brain tissue

• Cerebroside may contain either D-galactose or D-glucose

Steroids

• Cholesterol (major membrane component) (converted into progesterone, then testosterone)

• Bile salts (help in the digestion of fats)

• Ergosterol (yeast steroid which is converted into vitamin D by ultraviolet radiation)

• Digitalis (heart drugs)

• Adrenal cortex hormones (metabolism)

• Sex hormones

Atherosclerosis

Deposits of cholesterol and other lipids on the inner walls of the arteries

How are Proteins Numbered?

The chain is numbered from N-terminal on the left, and C-terminal on the right

Naming Proteins

• Ala-Tyr-Gly is called alanyltyrosylglycine

• C-terminal keeps its name, others end in 'ine', 'ic', or 'yl”

Protein Structure

Primary

• Covalent bonding

• Amino acid sequence of a protein

• Asp-Arg-Val-Tyr-Val-His-Pro-Phe

 

Secondary

• Three dimensional structure held together by hydrogen bonding (C=O) (H-N)

• Alpha helix

• Beta pleated sheet

• Beta sheets that have strands pointing in the same direction = parallel or strands pointing in opposite directions = antiparallel.  

 

Tertiary

• Shape or conformations of the protein

• R group interactions that stabilise tertiary structures

• Hydrogen bonding

• Ionic bonding

• Disulfide bonding

Quaternary

• Found in only some proteins

• Made from two or more smaller protein subunits or polypeptide chains

• Refers to the shape of the entire complex

• Noncovalent bonds like hydrogen bonding and ionic bonding

Protein Functions

1. Structural support (collagen)

2. Storage (ferritin stores iron in the liver)

3. Transport (haemoglobin moves oxygen in red blood cells)

4. Defence (antibodies)

5. Motion/movement (actin/myosin)

6. Regulation (insulin)

7. Catalysis (increases the reactions)

Proteins and their Structures

Fibrous Proteins

• Fiber-like shape

• Structural supports

• Tend to be water insoluble

• Alpha keratin is found in hair

• Fibroin (pleated sheet) is found in silk

• Collagen (helix) is found in many tissues

 

Globular Proteins

• Round

• Charged and polar amino acids are found on the outside of a protein structure and interacts with water

• Non-polar amino acids a buried in the interior of the protein and avoid water

• Myoglobin has and iron bound atom in the haem ring that allows is to store oxygen for muscle tissues

• Haemoglobin transports oxygen in red blood cells, 4 subunits and a haem ring

• Carboxypeptidase A, is a catalytic protein for digestion

• Fatty acid binding protein transports fatty acids through the blood stream

• Ferritin stores iron in the liver

• Myosin makes movement in muscles

Loss of Protein Structure

• Effect proteins function and is called denaturation

• Alterations or disruption of the secondary, tertiary, or quaternary structures

• Not primary

How Can Proteins be Denatured

• Heat (disrupting the weal interactions such as hydrogen bonding)

• pH (alter the net charge on the protein causing electrostatic repulsion and disruption of hydrogen bonds)

• Organic solvents, urea, guanidine HCl and detergents (disrupting the hydrophobic interactions)

• These do NOT break covalent bonds and so do NOT denature primary structures

 

• Hydrolysis of peptide bonds to make free amin acids with destroy the proteins primary structures

• Can be hydrolysed by boiling a solution containing a strong acid (HCl) or strong base (NaOH)

Minerals

Sodium, potassium, and chloride

• Maintain appropriate salt levels in body fluids

Calcium and magnesium

• Critical for bone and teeth health, enzyme function, nerve transmission, and blood clotting

 

• Trace elements are required in small amounts

• Iron is a notable exception, crucial for haemoglobin in blood and some enzymes

Metals

Metalloenzymes are enzyme proteins containing metal ions (metal cofactors), which are directly bound to the protein or to enzyme-bound nonprotein components (prosthetic groups such as )

 

Non-metalloenzymes, like haemoglobin and myoglobin are proteins that bind to oxygen for transport and storage respectively

Human DNA can extend to 10cm and yet is contained in a small nucleus

• DNA is looped around small aggregates of positively charged histone proteins

• And then by wrapping the structure into a tight coil called a solenoid

The phosphates are on the outside of the DNA structure along the backbone and are negatively charged

• To balance out these charges DNA phosphates groups form ionic bonds to cations such as Mg²⁺ or Ca²⁺ which are called counterions

• DNA counterions reduce the electrostatic repulsion between DNA molecules by screening the negative charges in their backbones

Redox Coenzymes

• Very important function is to carry electrons to the mitochondrial electron transport system

• As the coenzymes are oxidized, the molecular oxygen is reduced

Molecular Oxygen

• Other reduced products of O2 are dangerous

• Known as reactive oxygen species (ROS), and can react with and destroy cell molecules

• Since cells have to live with the danger of ROS, they have develop defence mechanisms including two important protective enzymes

• Superoxide dismutase= destroys superoxides, O2- by making hydrogen peroxide

• Catalase= converts the hydrogen peroxide into water

High Energy Phosphate Bonds

• Energy is made in the mitochondria, but must be transported throughout the cell

• This delivery system must carry relatively large amounts of energy and be easily accessible to cellular reactions

 

• The most common high energy phosphate bond is the phosphate anhydride bond

Muscle Fiber Can make Energy to Contract

Substrate Level Phosphorylation

• Energy is got from oxidation and used to form high energy phosphate bonds

• Goes from ADP to ATP

Oxidative Phosphorylation

• Uses energy from redox reactions to form ATP

• Done in the mitochondria

• Oxidizes the two coenzymes NADH (makes 3 moles of ATP) and FADH2 (makes 2 moles of ATP)

• Mitochondrial electron transport

• Energy is trapped when ADP turns into ATP