Unit 1 Pharmacy

What are degenerate orbitals and how should they be filled up?

Degenerate orbitals are orbitals that are at the same energy level. They should be filled according to Hund’s rule, which means each orbital should be singly filled before they start doubling up.

What are hybridised and unhybridised orbitals used to make?

Hybridised orbitals are used to make the stronger sigma bonds. Unhybridised orbitals are used to make the weaker pi bonds.

How is a drug affected by the medium it is dissolved in and what characteristics are dependent on the medium?

The ionisation state of a drug that contains weakly acidic or basic functional groups is dependent on the pH of the medium it is dissolved in.

The pH influences the drug’s solubility, the way it is formulated, absorption, distribution and its pharmacological activity.

How are functional groups capable of ionisation and what is pKa?

An acidic group is capable of ionisation when it gives a proton away to become negatively charged. A basic group is capable of ionisation when it gains a proton to become positively charged.

The pH at which the ionisation of a functional group is exactly 50% is called pKa.

What does a drug commonly react with and what does it trigger?

A drug commonly interacts with a protein. This causes a chain of events which gives the drug its medicinal properties.

What is an orbital?

An orbital is used to describe where an electron can be found within a certain degree of probability.

What is orbital hybridisation?

Orbital hybridisation is the concept of mixing atomic orbitals to form new hybrid orbitals. They have different shapes, energies and orientations compared to regular atomic orbitals.

How is an alkane affected by orbital hybridisation?

Overlapping sp³ orbitals on adjacent carbon atoms will create an alkane molecule where the carbon atoms all have the same tetrahedral geometry.

How is an alkene affected by orbital hybridisation?

In alkenes when the bond angles are at 120^o , 1 of the p orbitals is removed from the hybridisation. There would be 3sp² orbitals and the unused p orbital would remain at 90^o to the others.

What is a polypeptide?

Amino acids that are joined together by peptide bonds.

Which is the only amino acid that does not have a chiral centre?

Glycine

Which is the only amino acid that is not primary?

Proline and it is a secondary amine.

What does an agonist do?

Binds to a receptor and provides a function.

What are the characteristics of alpha helices?

They are coiled, flexible and elastic. They are also amphipathic which means they contain both hydrophobic and hydrophilic components.

What are the characteristics of beta pleated sheets?

They are flat, short, strong, not flexible and have short 5-10 amino acid runs. The side chains are arranged alternately on opposite sides of the strand. It can also be amphipathic like alpha helices.

Why is the bond between cytosine and guanine stronger than the one between adenine and thymine?

Between cytosine and guanine there are 3 hydrogen bonds. Between adenine and thymine there are only 2 hydrogen bonds.

What is cyclization?

The hydroxyl group on the second to last carbon in the cycle reacts with the carbonyl group.

What is the process of DNA replication?

1. Proceeds bidirectionally.

2. Helicase separates the DNA strands by breaking the hydrogen bonds holding the nucleotides together.

3. Topoisomerase reduces torsional strain and positive supercoils.

4. Single Stranded Binding proteins stabilises the isolated strands.

5. RNA primer is required to begin replication. The primer is called primase.

6. DNA polymer 3 adds nucleotides in the 5’ to 3’ direction.

7. Replication is semidiscontinuous. It is continuous in the leading strand but in the lagging strand it travels in the opposite direction away from the replication and there are gaps between the primers

8. After replication the DNA primer is replaced by DNA polymerase 1.

9. DNA ligase seals the gap in between the DNA primers.

What does amylose consist of and what is it held together by?

Amylose is made up of a straight chain of glucose monomers and they are held together by alpha 1-4 glycosidic bonds.

What does amylopectin consist of and what is it held together by?

Amylopectin is made up of a straight chain of glucose monomers and multiple side chains. The straight chain is held together by alpha 1-4 glycosidic bond and the branches are held together by alpha 1-6 glycosidic bonds.

Where is cellulose found, what is it used for and what is it held together by?

Cellulose is found in plants, it is used for structural support by forming long fibres and they are held together by beta 1-4 glycosidic bonds.

What are the characteristics of lipids?

They are not polymers, non-polar, insoluble in water and soluble in non-polar solvents

What is inside the core and on the surface of lipoproteins?

Inside the core there is triglycerides, esterified cholesterol and phospholipids. The core is hydrophobic. On the surface there are apoproteins, phospholipids and cholesterol.

What are the 5 types of lipoproteins?

1. Chylomicron

2. Very Low Density Lipoprotein

3. Intermediate Density Lipoprotein

4. Low Density Lipoprotein

5. High Density Lipoprotein

In this order they get smaller in size and more dense. They also decrease in triglyceride content in this order.

Chylomicrons

Secreted by: ?

Lipid source: ?

Main lipid: ?

Transport: ?

They are secreted by enterocytes in the small intestine.

Their lipid source is dietary

The main lipid is triglycerides

It transports dietary triglycerides to peripheral tissues

VLDL

Secreted by: ?

Lipid source: ?

Main lipid: ?

Transport: ?

It is secreted by hepatocytes in the liver

Their lipid source is they are stored/synthesised in the liver

Their main lipid is triglycerides

They transport synthesised triglycerides to peripheral tissues

IDL

Source: ?

Formed in: ?

Main lipid: ?

End: ?

The source is VLDL degradation

They are formed in blood circulation

The main lipid is equally triglycerides and cholesterol

It ends in uptake by the liver or becomes an LDL

LDL

Source: ?

Formed in: ?

Main lipid: ?

Transport: ?

Its source is IDL degradation

It is formed in circulation of hepatic sinusoids

Its main lipid is cholesterol

They transport synthesised cholesterol to tissues

HDL

Secreted by: ?

Main content: ?

Roles: ?

It is secreted by the liver and small intestines

Its main content is proteins

Its main roles are both scavenging lipids, especially cholesterol and Donating Apo E and Apo C-II to VLDL and CM.

What are the lipoprotein values?

HDL: > 60mg/dL

LDL: 60-130mg/dL

Triglycerides: < 150mg/dL

Cholesterol: < 200 mg/dL

How does a drug work?

A ligand such as a hormone or a neurotransmitter binds to the specific receptor and leads to a biological response. Drugs that mimic the ligand can bind to the receptor and produce the same response. These are called agonists. Other drugs work in the opposite way. They bind to the receptor but do not produce a response. These are antagonists. They have an inhibitory effect as they stop the ligand from binding to its specific recpetor.

What are CDK Inhibitors and what do they do?

They are a family of enzymes involved in the regulation of the cell cycle.The aberrant expression is involved in cancer. They catalyse phosphorylation using ATP.

What is Lipinski’s rule of 5?

The molecular weight must be less than or equal to 500 Da to ensure the molecule is small enough to cross cell membranes. Lipophilicity must be less than or equal to 5. It allows balanced water solubility for dissolution and fat solubility for membrane permeability. Hydrogen bond donors must be less than or equal to 5. This is the sum of OH and NH groups; high donor counts, impedes passive diffusion. Hydrogen bond acceptors must be less than or equal to 10. This is the sum of N and O atoms; high acceptor counts = lower permeability.

Discuss enantiomers and give an example.

Most often only 1 enantiomer shows correct physiological and pharmacological action. For example, 1 enantiomer of morphine is analgesic. In practise, companies market racemic mixtures as chiral synthesis is too expensive. A racemic mixture is a 50/50 mixture of 2 enantiomers. Morphine will be left in a mixture but only the analgesic variant will take action.

What is a chiral diastereoisomer?

Chiral isomers which are not enantiomers. They differ in physical, chemical and biological properties. They can only be found in molecules with multiple chiral centres.

What is the electronegativity in order from highest to lowest?

F — O — Cl — N — Br — C — I — S — P — H

What happens in a covalent bond regarding electronegativity?

In a covalent bond electrons are shared equally between the 2 atoms. If 1 atom has greater electronegativity, electron density shifts towards it and creates a partial charge, creating a polar covalent bond.

Explain amino acids and their structure.

Amino acids are a class of molecules that contain an acidic group and an amine group. With the exception of glycine, the alpha C atoms in the amino acids are all chiral centres. Amino acids also have at least 2 or for those with an ionisable side chain 3 acid-base groups. Amino acids are also amphoteric, this means they can either act as a base or an acid.

What are the categories of proteins and what are their functions?

Structural: Provide structural support and framework for the cells and body e.g. Collagen.

Movement: Main components in muscles e.g. Actin and Myosin.

Transport: In cell membranes they allow the movement of molecules in and out of cells.

Metabolic: Enzymes that synthesise and catalyse the breakdown of biological macromolecules to maintain cellular function.

Communication: Hormones and neurotransmitters control various biological activities by binding to specific cellular receptors.

Defence and Protection: They contribute to the barrier properties of skin e.g. keratins and antibodies which play a major role in the immune system.

What are the 4 main structure levels for proteins?

Primary: The simple linear sequence of amino acids in the polypeptide chain of a protein

Secondary: The alpha helix and beta pleated sheets secondary structures. In alpha helix, H bonds form between the O of a carbonyl group and the amide group of the amino acid 4 places down the strand. Side chains point outwards from the densely populated core, improving stability of the helix. In the beta pleated sheet H bonds are formed between polypeptide chains lying adjacent to each other.

Tertiary: The complex coiling and folding of secondary structure elements that establishes the final 3D structure of the protein. The final structure is the result of the interaction between the side amino acid chains and also between the polypeptide chain and surrounding water molecules.

Quaternary: Describes the interaction between separate polypeptides to form a multi-subunit protein complex.

What is the structure of Globular proteins?

They typically have an irregular, rounded shape e.g. Myoglobin, haemoglobin, hormones and enzymes. Their core is made up of non-polar amino acid residues. The charged and polar residues coat the outer surface. These proteins are readily soluble in the cytoplasm.

What is the structure of Fibrous proteins?

These have linear helical or sheet-like structures. This is typically due either to association of secondary structure domains of individual beta sheet structures. It can also be due to quaternary association of several individual sheets. These are tough and insoluble in water.

What are nucleic acids?

Organic compounds that are composed of C, H, O, N and P. They encode all the information needed to build various structural and functional proteins in the form of genes. The forms of these are DNA and RNA.

What is the process of transcription?

Double stranded DNA is transcribed to produce single stranded RNA. 3 types of RNA are messenger, ribosomal and transfer. They all participate in translation. Messenger RNA carries the genetic code from the nucleus to the cytoplasm to make proteins.

What are vitamins?

They are organic compounds that act as cofactors for enzyme reactions in various essential physiological processes. Fat-soluble vitamins can be stored long term in the body, water-soluble vitamins are readily excreted. Vitamins are also named in alphabetical order in the time they were discovered.

What is Vitamin B1/Thiamin?

Concentrated in tissues that are high in carbohydrates. It is essential for carbohydrate metabolism, growth and development. TPP is a prosthetic group of several enzymes involved in the generation of intermediates in the Kreb’s cycle.

What is Vitamin B2/Riboflavin?

Riboflavin often exists as FMN or FAD which are prosthetic groups in a variety of respiratory enzymes involved in energy release.

What is Vitamin B3/Niacin?

Good sources of Niacin include meat, fruit and vegetables. Niacin is essential for energy metabolism.

What is Vitamin B6/Pyridoxal-5-phosphate?

It exists in multiple forms: Pyridoxine (B6 supplement), Pyridoxol (Found in plants) and Pyridoxamine (Found in foods of animal origin). B6 molecules are prosthetic groups to a variety of enzymes involved in amino acid/glucose/lipid metabolism and the synthesis of haemoglobin.

What is Vitamin B7/Biotin?

Found in most foods. It is a prosthetic group that is involved on the metabolism of amino acid/glucose/lipid.

What is vitamin B9/Folic Acid?

Good sources of B9 include liver and leafy green vegetables. Tetrahydrofolic Acid and 5-methyltetrahydrofolate are co-enzymes in the metabolism of 1 carbon units.

What is Vitamin B12/Cobalamin?

B12 is synthesised by bacteria. Good sources of B12 include liver, meat, eggs and milk. It is a co-enzyme responsible for the metabolism of 1 carbon units.

What is Vitamin C?

Good sources of Vitamin C include fruits and vegetables. The best source is potatoes. Vitamin C refers to both ascorbic acid and dehydro-ascorbic acid. Ascorbic acid is an antioxidant and enzymatic co-factor for hydroxylation reactions. It is necessary for the formation of collagen and production of noradrenaline from dopamine.

What is Vitamin A/Retinol?

Good sources of Retinol include butter, cheese and cod liver oil. Vitamin A is essential for vision and plays a role in bone metabolism.

What is Vitamin D?