Unit 1: Fundamental Chemistry of Drugs and Molecules of Life Flashcards

Question

An ionised compound is...

Answer 1

more soluble in water than in non-polar solvents

Answer 2

Be sufficiently soluble in water to dissolve in blood plasma and be carried around the body (to reach area where needed) while also being sufficiently soluble in non-polar lipids to pass through cell membranes into cells (and carry out function)

Answer 3

pH > pKa higher pH is more basic, so acid is in its conjugate base form

Answer 4

pH < pKa lower pH is more acidic, so base is in its conjugate acid form

Answer 5

species that forms when a base gains a proton

Answer 6

species that forms when an acid donates a proton

Answer 7

sharing electrons by overlap of an sp2 orbital from each atom forming a strong single bond electron density concentrated between nuclei

Answer 8

Overlap of the parallel p-orbitals forms an orbital that places a cloud of electrons above and below the sigma (single) bond

Answer 9

Hybridisation- sp3 Shape- Tetrahedral

Answer 10

Hybridisation- sp2 Shape- Trigonal

Answer 11

Hybridisation- sp Shape- Linear

Answer 12

* The clinical efficacy of a drug is critically dependent on its three-dimensional structure * The stereochemistry of a drug can impact upon its toxicity and side effects

Answer 13

structures that are nonsuperposable mirror images of one another

Answer 14

painkiller

Answer 15

their ability to rotate the plane of polarised light, they are often referred to as optical isomers

Answer 16

Usually only one enantiomer will interact fully with the receptor Drugs should optimally be administered as single enantiomers

Answer 17

Inactive Producing side effects Countering the effect of the drug Being metabolised to a toxic product

Answer 18

Companies market racemic mixtures of synthetic drugs if they can. This can be risky

Answer 19

anticlockwise

Answer 20

Step 1. Assign “priority” to each atom attached to the chiral centre (according to atomic number). Step 2. View the molecule with the lowest priority (4th) group (often H) directed away from the observer. Step 3. Observe the order of priority: join the 1, 2, 3 groups together, if the direction is clockwise, the isomer is rectus (R), if anticlockwise sinister (S) (Figure 15). Step 4. If two or more atoms attached to a chiral centre are the same, look to second and third atoms until it is possible to distinguish between groups. The highest priority different atom takes precedence; you do not add the atomic numbers together. Step 5. For multiple bonds, treat as single bonds to duplicate or triplicate atoms of the same type.

Answer 21

are stereoisomers of each other but they are not specifically mirror images of each other

Answer 22

found in molecules with double bonds and saturated rings

Answer 23

Chiral isomers which are not enantiomers, i.e. not mirror images of each other.

Answer 24

an equal mixture of both enantiomers of a compound, has no measurable optical rotation

Answer 25

Electrostatic Hydrophobic

Answer 26

Forms when electronegative N, O, F approach a hydrogen atom covalently attached to another electronegative atom, e.g. between carbonyl and amino group.

Answer 27

Electrostatic like H bonds but distance between interacting groups isn't fixed and alignment isn't as important. Any group/atom in a molecule which carries a charge (electronegativity difference between atoms the presence of an acidic or basic group, or an atom with a lone pair of electrons) Can be attractive or repulsive.

Answer 28

pH-dependent e.g. with proteins- the carboxyl group loses the proton and the amino group gains the proton

Answer 29

Hydrophobic groups are insoluble, do not contain any particularly electronegative atoms, e.g. CH3. -- Neutral groups- which have no way of interacting with water. -- Apolar groups do not interact or repel each other, but rather come together through the action of the water solvent

Answer 30

Contains an acidic group (carboxylic group), basic group (amine), R group, H atom

Answer 31

They all have an amino group on the first (α) carbon atom adjacent to the carboxylic acid group They are primary amino acids since they have a primary amine group Exception is proline- it has a secondary amine group.

Answer 32

Non polar (straight or branched chains that may or may not be cyclical) Aromatic Uncharged polar Charged (negative/acidic or positive/basic side chains) Sulphur containing

Answer 33

The carboxylic group is unionised while the amino group is in its ammonium ionised state Protonated form

Answer 34

The carboxylic acid group in its ionised carboxylate form while the amino group is in its non-ionised state Deprotonated form >pKa2

Answer 35

Around neutral pH Both groups ionised Zero net charge

Answer 36

Structural proteins, e.g. collagen Movement proteins e.g. myosin Transporter proteins e.g. GLUT family of glucose transporters Metabolic proteins e.g. hexokinase Communication proteins e.g. insulin Defence and protection e.g keratin, antibodies, thrombin

Answer 37

Enzymes that catalyse the breakdown and synthesis of biological macromolecules to maintain cellular function

Answer 38

Converts glucose to glucose-6-phosphate, first step in glycolysis

Answer 39

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

Answer 40

Local arrangement of amino acids with respect to each other to form defined, hydrogen-bonded structures.

Answer 41

H bonds form between Oxygen atom of carbonyl group and NH hydrogen of amine group 4 places down the strand.

Answer 42

Improves stability of the helix by preventing steric hinderance.

Answer 43

Hydrogen bonds formed between peptide chains lying adjacent to eachother Parallel sheets occur when these strands run from N to C terminals in the same direction. Anti-parallel sheets occurs when protein strand folds back on itself

Answer 44

Complex coiling and folding of secondary structure elements that determines the 3D structure of the protein.

Answer 45

Interaction between individual polpeptides to form multisubunit protein complex.

Answer 46

Have irregular, rounded shape E.g. myoglobin, haemoglobin, hormones (insulin) and enzymes. Core typically made of non-polar amino acid residues, outer surface is usually charged and polar. These proteins are readily soluble in cytoplasm and other aqueous environments Make use to alpha helixes.

Answer 47

Linear helical or sheet-like structures Usually due to association of secondary structures (e.g. collagen triple helix) Or due to quaternary association of several individual sheets (e.g. keratin) Tough, usually water insoluble, protective or structural role in body

Answer 48

Due to the substitution of a single amino acid in haemoglobin (termed HgbS) resulting in a mutated haemoglobin with a different primary sequence.

Answer 49

Normal RBC are quite elastic, which allows the cells to deform to pass through capillaries. In sickle-cell disease, low oxygen tension alters the shape of haemoglobin, and promotes RBC sickling (bending to a curved shape) which damages the cell membrane and decreases elasticity. These cells fail to return to normal shape when normal oxygen tension is restored. Rigid blood cells are unable to deform as they pass through narrow capillaries, leading to vessel occlusion and ischaemia.

Answer 50

by faster than normal destruction of the red cells because of their altered shape

Answer 51

where non-polar substances combine in aqueous solution, minimising disruption to the hydrogen bonds between water molecules

Answer 52

high molecular weights can make proteins hard to crystallise. Sugars, such as mannitol and sucrose can be added

Answer 53

If proteins removed from their environment- activity can be lost. Interactions between hydrophobic amino acid residues can minimised SA exposure to water. Freeze-drying of proteins can enhance their stability and shelf life.

Answer 54

Consists of two biopolymer strands coiled around each other to form a double helix Specific bases (adenine, guanine, thymine and cytosine) interact in defined pairs. A is always paired with T, and G is always paired with C These interactions occur via hydrogen bonding

Answer 55

Double stranded DNA is transcribed to produce single stranded RNA. Three major types of RNA (messenger; ribosomal and transfer) are transcribed from DNA and participate in the process of translation Messenger RNA (mRNA) is the type of RNA that carries the genetic code required to make proteins.

Answer 56

mRNA is translated into proteins in the cytoplasm on ribosomes. tRNA carries individual amino acids to the ribosomes, where they are joined in via peptide bonds to form proteins. During translation, the sequence of nucleic acid bases in mRNA is read in sets of three (each set of three bases constitutes a codon). The sequence of codons in the mRNA dictates the sequence of amino acids in the protein. Thus, DNA is said to comprise an organism’s “genetic code”.

Answer 57

the use of molecular methods to modify and engineer the genetic material of living cells so they will produce new substances and/or perform new functions

Answer 58

medical tests that identify molecular changes in chromosomes, genes, or proteins e.g. downs syndrome testing, or sickle cell disease testing

Answer 59

an individual patient's “single nucleotide polymorphisms" can help predict how quickly they will metabolise particular drugs e.g. the liver enzyme CYP2C19 metabolises several medicines, including the antiplatelet medicine clopidogrel (prodrug) Some patients possess SNPs in specific places on the CYP2C19 gene that make it a poor metaboliser of Clopidogrel.

Answer 60

hese are critical energy stores in animals and plants respectively. In mammals, glycogen is synthesised and stored in liver and skeletal muscle.

Answer 61

this is the fundamental structural component of plant cell walls

Answer 62

Carbohydrates of intermediate chain length (between 3 and 10 monomers)

Answer 63

β-lactose is twice as sweet as α-lactose. α-lactose has better powderflow properties and therefore is more commonly used as an additive in pharmaceutical industry for tablet production than β-lactose

Answer 64

oxygen content of lipids is much less than that of carbohydrates, meaning that lipids are typically water insoluble.

Answer 65

double bonded

Answer 66

3 fatty acid and 1 glycerol

Answer 67

Essential for cell membrane fluidity and is a metabolic precursor for bile, the active form of vitamin D and all estrogens. Cholesterol is transported using special carriers called lipoproteins. LDL (low density lipoproteins) essentially transport cholesterol from liver and intestine to the rest of the body. Meanwhile HDLs (high density lipoproteins) remove excess cholesterol and transfer it back to the liver.

Answer 68

high levels of LDL cholesterol in the blood

Answer 69

statins- atorvastatin

Answer 70

A potent competitive inhibitor of HMG-CoA reductase. This enzyme plays a pivotal role in producing mevalonic acid, which is an upstream precursor to cholesterol. Inhibition of this rate- limiting step decreases cholesterol production and also the production of a variety of isoprenoids that may have roles in pro-inflammatory signalling

Answer 71

Can be stored long term in the body Vitamin A, D, E, K

Answer 72

Readily excreted B complex and vitamin C

Answer 73

Vitamin B1/Thiamin Vitamin B2/Riboflavin Vitamin B3/Niacin Vitamin B6 Vitamin B7/Biotin Vitamin B9/Folic acid Vitamin B12/Cobalamin

Answer 74

Widespread in both animal and plant kingdoms- in tissues high in carbohydrates/associated with carbohydrate metabolism.

Answer 75

Thiamine diphosphate/thiamine pyrophosphate (TPP) or as triphosphate.

Answer 76

Carbohydrate metabolism- growth and development.

Answer 77

Beriberi Weight loss, sensory/cognitive dysfunction, weak/painful limbs, heart problems

Answer 78

Exists predominantly as flavin mononucleotide (FMN) or flavinadenine dinucleotide (FAD) which are prosthetic groups in a variety of respiratory enzymes involved in energy release

Answer 79

deficiency can lead to ariboflavinosis, causes stomatitis of the mouth and tongue, cheilosis (chapped and fissured lips) and a scaly rash on the genitalia.

Answer 80

name given to both nicotinic acid and its amide

Answer 81

Meats, fruits and vegetables

Answer 82

occurs in vivo as part of the co-enzymes NAD and NADP, and is thus essential for energy metabolism

Answer 83

results in pellagra, the pathological impact of which is broad and results in death if not treated

Answer 84

pyridoxal-5-phosphate exists as a variety of interconvertible forms such as pyridoxine (most common B6 supplement) pyridoxol (only found in plants) and pyridoxamine (only found in foods of animal origin), all of which can also be phosphorylated.

Answer 85

Meat, egg yolk, and wheatgerm are abundant sources with less found in milk and cheese

Answer 86

B6 molecules are prosthetic groups to a variety of enzymes involved in amino acid/glucose/lipid metabolism, and the synthesis of haemoglobin

Answer 87

whilst deficiency symptoms are similar to those for other “Bcomplex” vitamins, anaemia is also possible

Answer 88

Biotin is a prosthetic group in enzymes that play a role in amino acid/glucose/lipid metabolism

Answer 89

Deficiency is rare, but can happen when patients utilise parenteral nutrition (IV) for long periods.

Answer 90

as a group of polyglutamyl conjugates

Answer 91

Liver and leafy green vegetables are good sources

Answer 92

Tetrahydrofolic acid and its 5-methyl form (5-methyltetrahydrofolate) are major active forms in vivo, co-enzymes in the metabolism of one-carbon units, the production of nucleotides, nucleic acids, and the metabolism of haem.

Answer 93

Folic acid deficiency is most commonly associated with complications in pregnancy – babies are more likely to be premature, with low birth weight and an increased risk of neural tube defects, such as spina bifida. Recommended that folic acid is taken while attempting to get pregnant until 12 weeks pregnant.

Answer 94

Synthesised by bacteria, meaning there is little to be found in dietary plants. Liver, meat, eggs and milk are good sources

Answer 95

Cobalamin is a co-enzyme responsible for metabolism of one-carbon units, DNA synthesis and formation of red blood cells.

Answer 96

When ingested, vitamin B12 combines with a protein in the stomach called “intrinsic factor”. This mix of vitamin B12 and intrinsic factor is then absorbed in the distal ileum. Pernicious anaemia causes your immune system to attack the cells in your stomach that produce intrinsic factor, which makes your body unable to absorb vitamin B12.

Answer 97

both ascorbic acid and its oxidised form dehydro-ascorbic acid (DHAA)

Answer 98

Fruits and vegetables are the best source of ascorbic acid. However, the major source of vitamin C in the British diet is the potato

Answer 99

Known as antioxidant But is an enzymatic co-factor for hydroxylation reactions, and thus necessary for the formation of collagen (cartilage, scar tissue, blood vessels) and the production of noradrenaline from dopamine. Ascorbic acid also enhances the uptake of dietary non-haem iron

Answer 100

a molecule that increases the rate of reaction or is required for enzyme function

Answer 101

responsible for scurvy, whereby insufficient cross linking of collagen results in slow healing of wounds, bleeding gums and mucous membranes, tooth loss, pale skin and nervous dysfunction.

Answer 102

. Butter, cheese and cod liver oil are good sources

Answer 103

Vitamin A derived from animal tissues has a high degree of bioavailability and is rapidly absorbed. Retinyl esters of long chain fatty acids are hydrolysed then re-esterified by intestinal mucosa during absorption, then bound by retinol-binding protein in the liver. This form can be released from the liver as needed, and subsequently hydrolysed to retinol.

Answer 104

absorbed after the conversion of carotenoids (yellow/orange pigments) to retinol in the small intestine. Conversion to retinol is adaptive and inversely related to β-carotene intake, meaning the risk of vitamin A toxicity from consuming plant sources is low

Answer 105

is used to produce rhodopsin also plays a role in bone metabolism, whilst retinoic acid is necessary for gene transcription, reproduction and skin health. carotenoids and vitamin A also have antioxidant activity.

Answer 106

night blindness and skin legions. Acute cases can lead to abnormal bone development, reproductive disorders and death.

Answer 107

cholecalciferol

Answer 108

Made in the skin in sunlight through the conversion of an intermediate in the cholesterol cycle Cholecalciferol can be found in dairy products and egg yolk but oily fish is the best source

Answer 109

Cholecalciferol is converted in the liver to calcifediol which is converted to calcitriol (the active form of vitamin D) in the kidneys. Calcitriol increases blood levels of calcium by increasing its uptake in the intestine (along with its phosphate counterion), and through increased resorption of bone mineral.

Answer 110

Deficiency can result in rickets, which causes bones to become soft and weak, which can lead to bone deformities

Answer 111

potent antioxidant, responsible for protecting lipids in cell membranes from oxidative damage

Answer 112

Due to their role carrying oxygen around the body, red blood cells are at particular risk of oxidation in vitamin E-deficient patients.

Answer 113

a group of compounds containing an active naphthoquinone ring

Answer 114

Vitamin K1 is phylloquinone produced during photosynthesis and is therefore found at highest levels in leafy green vegetables

Answer 115

The vitamin K2 group are the menaquinones. Whilst K2 compounds are found in meat, eggs and dairy products, our own gut bacteria also produce them.

Answer 116

blood clotting/coagulation as it is a co-factor for a liver enzyme required to carboxylate glutamate residues to make them fully functional

Answer 117

leads to bleeding disorders

Answer 118

which is given to reduce risk of coagulation in patients at risk of developing clots works by binding vitamin K epoxide reductase, the enzyme that recycles oxidized vitamin K1 to its active reduced form

Answer 119

separate (non-protein) molecules or ions that must bind with an enzyme to make it work, either by joining with the active site directly, or by stimulating a conformational change to the protein that (in turn) changes the shape of the active site can be referred to as co enzymes

Answer 120

a foreign compound taken into an organism that changes the behaviour of a biological process for therapeutic benefit

Answer 121

that most medicinal drugs were relatively small, lipophilic molecules

Answer 122

says that a molecule of an orally active drug usually obeys at least three of the following criteria: * Not more than 5 hydrogen bond donors, e.g., an alcohol group, -OH, or an amine group (primary, -NH2, or secondary, -NHR); * Not more than 10 hydrogen bond acceptors, nitrogen atoms, N, or oxygen atoms, O; * A relative molecular mass of less than 500; * An octanol-water partition coefficient logP not greater than 5.

Answer 123

the specific chemical constituents of the cell with which a drug interacts to produce its pharmacological effects

Answer 124

A platinum-based anticancer drug, exerts its therapeutic effect by platinating the N-7 position of guanine on the major groove site of the DNA double helix (Figure 34). This chemical modification of the platinum atom crosslinks two adjacent guanines on the same DNA strand. This blocks replication and inhibits transcription, resulting in DNA damage and subsequently cell death.

Answer 125

interaction between the protonated amino group on salbutamol (inhaler to relieve asthma and breathlessness) and the dissociated carboxylic acid group of its receptor site .