Week 4 Day 2: Action Potential, Synaptic trans, Pur & Py, Folate & B12

Question 1

What does methotrexate (MTX) affect and overall what does it inhibit? And when would you NOT want to give it?

Answer 1

MTX inhibits dihydrofolate reductase (which catalyzes the reduction of dihydrofolate to tetrahydrofolate (THF)) leading to a lack of THF.
This results in an inability to synthesize thymidine as well as purine nucleotides.
This inhibits DNA and RNA synthesis and thus inhibits cell proliferation.
Don’t give it during pregnancy (unless it is ectopic)

Question 2

What is megaloblastic anemia? How does it present in pts? What is it caused from? And what is the treatment?

Answer 2

Megaloblatic anemia is an accumulation of immature RBC in bone marrow
Presentation: pale, tired, fatigued
Causes: Folate or B12 deficiency
Treatment: Oral Folate or B12

Question 3

In addition to causing megeloblastic anemia, name something else B12/ folate deficiency can cause. And what is it caused from?

Answer 3

B12 can also cause irreversible nerve damage due to demyelination of the nerves.
Cause by a blockage of the methylmalonyl mutase that requires vitamin B12.

Question 4

What is intrinsic factor? Low intrinsic factor is seen a lot in what type of patient? What does it cause? How do you treat it?

Answer 4

A protein produced by the stomach and necessary for vitamin uptake in the small intestine.
Seen a lot with old patients bc their intrinsic factor production decreases with age.
It causes pernicious anemia bc unable to take in B12 leading to B12 deficiency
Treatment is B12 IM

Question 5

What is gout? What causes it?

Answer 5

Gout is an accumulation of uric acid in the joints.
Caused by elevated uric acid levels due to:
1. defects in renal excretion (unable to excrete uric acid through kidneys)
2. excess degradation of purines (caused by trauma, diet or cancer therapy)

Question 6

Describe the enzyme deficiency that causes Lesch-Nyhan syndrome (and gout)

Answer 6

A deficiency in hypoxanthine guanine phosphoribosyl transferase (HGPRT) leads to a build up of guanine bc it is unable to convert to nucleotide GMP so excess guanine is broken down to uric acid.
Lesch-Nyhan syndrom is X-linked

Question 7

Treatment for gout is allopurinol which prevents what?

Answer 7

Allopurinol prevents xanthine oxidase from converting hypoxanthine –> xanthine and xanthine –> uric acid

Question 8

What is orotic aciduria (OA)?

Answer 8

A deficiency in UMP synthase for de novo synthesis of pyrimidines.
It causes megaloblastic marrow.
Consequences: bladder stones, mild retardation, and megaloblastic anemia.

Question 9

What is FdUMP?

Answer 9

FdUMP, a suicide inhibitor of thymidylate synthase (TS) which converts dUMP –> dTMP for thyamine biosynthesis for DNA.
Used in the treatment of cancer including colorectal and breast cancer and cancers of the aerodigestive tract

Question 10

What is Methotrexate (MTX)?

Answer 10

Methotrexate (MTX) interfers with purine biosynthesis preventing dihydrofolate –> tetrahydrofolate (THF)
MTX is used to treat cancer by preventing proliferation of cancer cells

Question 11

What is the function of ribonucleotide reductase?

Answer 11

To reduce ribose to deoxyribose. Keeps the pool of nucleotides balanced.

Question 12

When is Allopurinol used? And what does the drug Allopurinol do?

Answer 12

Used to treat gout due to hyperuricemia.

Allopurinol is a suicide inhibitor of xanthine oxidase which converts hypoxanthine –> uric acid.

Question 13

A B12 deficiency can cause??

Answer 13

Prevents the conversion of homocysteine to methionine causing a build up of homocysteine leading to megaloblastic anemia.
Long term deficiency prevents the conversion of methylmalonyl CoA to succinyl CoA causing nerve damage (demyelination)
**Seen a lot with older people

Question 14

How do changes in the resting membrane potential effect voltage and excitability?

Answer 14

Causes changes in voltage difference between resting membrane potential and action potential which changes its excitability.

Question 15

A cell with a more positive (less negative) resting membrane potential will be _____ excitable.

Answer 15

More easily

Question 16

What two ions play an important role in setting the resting membrane potential of muscle?

Answer 16

Cl- and K+

Question 17

Loss-of-function of Cl- channels in muscles causes the resting membrane potential to ________ and have ______ excitability.

Answer 17

depolarize and have increased excitability.

Question 18

What are three factors that control speed of propagation?

Answer 18

1. Axon diameter: larger diameter –> increased internal conductance –> faster propagation
2. Capacitance: increased capacitance –> slower propagation
3. Myelination: allows for faster propagation bc reduces capacitance, increases membrane resistance, and increases internal conductance.

Question 19

What ion is required for the release of neurotransmitters at the presynaptic membrane?

Answer 19

Ca2+

Question 20

Describe EPSP

Answer 20

Makes a postsynaptic neuron more likely to generate an AP by depolarizing via influx of Na+

Question 21

Describe IPSP

Answer 21

Makes a postsynaptic neuron less likely to generate an AP by hyperpolarizing via efflux of K+ or influx of Cl-

Question 22

Describe an ionotropic receptor

Answer 22

FAST receptor! A receptor that also acts as an ion channel

Question 23

Describe a metatropic receptor

Answer 23

SLOW receptor. A GPCR that must initiate a cascade

Question 24

What is an example of a fast EPSP transmitter in the CNS?

Answer 24

Glutamate

Question 25

What is an example of a fast IPSP transmitter in the CNS?

Answer 25

GABA

Question 26

What is an example of a slow IPSP transmitter in the CNS?

Answer 26

GABA

Question 27

Describe temporal integration

Answer 27

Time between APs in the presynaptic is shorter than the potential produced in the post causing AP to build up.

Question 28

Describe spatial integration

Answer 28

Synaptic potentials produced at similar times from different synapses.

Question 29

What do gap junctions work to accomplish?

Answer 29

Current flowing between the gap junction will work to equilize the voltage in the two cells of similar resistance.

Question 30

What is an example of a fast IPSP transmitter in the CNS?

Answer 30

Local anesthetics are conduction blockers. They bind to S6 subunit to prevent Na+ from entering pore. By inactivating Na+ channels, the threshold for axonal excitation becomes more unattainable and the refractory period is increased as more and more Na+ channels become unavailable.

Question 31

How does demyelination affect action potential and why?

Answer 31

Demyelination causes loss of saltatory conduction. Linear conduction along demyelinated axons is slow because the internodal axon membrane has few ion channels (some ion channels may diffuse from nodal region but not enough to reproduce the action potential continuously along the length of the axon).
In addition, lack of insulation of axons allows impulses to disperse laterally to adjacent demyelinated axons. The abnormal physiology of demyelinated axons results in inefficient conduction or conduction block.