Bchm 480

...

3) Describe the difference between a Scatchard plot of a single binding site and the plot of multiple binding sites with multiple Kd’s.

Single binding site = linear

Multiple = curved

4) Why are enantiomers generally not ligands for the same receptors?

Being mirror images, enantiomers would have opposite pharmacophores

5) Why does the basement membrane provide less of a barrier for a drug to cross than the cell membrane?

The cell membrane creates a semi-permeable barrier with polar and non-polar regions. The basement membrane is more like a net excluding things based solely on size.

6) Describe the structure of the Brain-Blood barrier.

In a blood vessel, there are epithelial cells surrounded by basement membrane with space between the epithelial cells. In the brain blood barrier, there is no space between the epithelial cells. Also surrounding the basement membrane, there are glial cells. Meaning something crossing the Brain-blood barrier has to cross 4 cell membranes and 1 basement membrane

7) A Compound has a maximum solubility in Octanol of 100 mM and a maximum solubility of 100 nM. Is this compound a good candidate for pharmaceutical use? Why or why not?

K = [octanol]/[H2O] = 0.001/1x10-9 = 1x106 p = log k = 6

Would prefer p

8) Describe how the kidney filters the blood and uses OAT/OCT and ion transporters to determine what is excreted in the urine.

In the glomerulus, blood is filtered through the basement membrane. This excretes ~50% of everything from the blood. The process is fine tuned in the loop of Henle where OAT/OCT export larger organic molecules and ion transporters reabsorb most of the ions.

9) Describe the basic activity of the enzyme responsible for most phase 1 detoxification reactions.

Cytochrome P450 is a heme containing monoxygenase. The iron in heme binds and activates dioxygen, one oxygen atom is reduced to water, leaving the other oxygen atom activated to attack organic substrate.

10) What are the main structural features found in all classes of GPCR?

GPCRs are 7 transmembrane α helix proteins, with extracellular three loops and the n-terminus and intracellular three loops and c-terminus.

11) What are the 5 ion channels and pumps you are required to remember?

Na/K ATPase

Ca ATPase

Na/Ca transporter

K/Cl transporter

K Channel

12) What is the order of opening of the ions channels in the firing of a neuron starting from initial signal to release of neurotransmitter.

Na – Ligand gated channel

Na – voltage gated channel

K- voltage gated channel

Ca-voltage gated channel

13) How does the order from question 12 change if the excitatory cell is a cardiac worker cell?

In a neuron, the Ca-voltage channel is involved only at the end to stimulate the release of neurotransmitter. In the worker cell, the Ca channel fires sooner as part of the action potential to extend the length of the action potential. So technically the order is the same but the Ca is sooner and part of the action potential

14) What are the difference between the α1, α2, β1 and β2 adrenergic receptors?

α1 – norepinephrine and epinephrine – Constriction of smooth muscle

a2 – norepinephrine and epinephrine – suppress the release of norepinephrine

b1 – epinephrine – increase cardiac outpur

b2 – epinephrine – relax smooth muscle

15) How would a Ca channel blocker affect the action potential of a neuron? Of a cardiac worker cell?

In neuron – it would block the release of the neurotransmitter.

In worker cell, it would shorten the action potential.

16) What is the main role of the Hypothalamus and the Pituitary in the endocrine system?

The Hypothalamus controls pituitary by releasing factors and inhibitory factors

Pituitary hormones stimulate release of other hormones from targets.

17) What is the structural difference between the T3 and T4 Thyroid hormone?

T3 has one less Iodine

18) Describe how the typical Steroid Receptor works,

Steroid ligand binding drives dimerization. Dimerized Receptors are transcription factors.