Biochem: Intro NTs and DA

Question 1

What structural feature do all catecholamines share?

Answer 1

Benzene ring with two adjacent secondary alcohol functional groups.
(catechol)

Question 2

Designer drug that lead to drug-induced Parkinson’s Disease in patients.

Answer 2

MPPP

metabolized to MPTP in the body, then metabolized into MPP+ by MAO which is toxic to the substantia nigra

Question 3

What are Lewy Bodies?

Answer 3

Eosinophilic inclusion bodies found in Substantia Nigra tissue viewed under a microscope. They are indicators of Parkinson’s Disease

Question 4

Name the 2 locations in the CNS where Dopamnergic neuronal CELL BODIES are located.

Answer 4

1. Substantia Nigra Pars Compacta (portion of the substantia nigra that makes DA)
2. Ventral Tegmental Area (located just posterior to the interpeduncular fossa of the midbrain)

Question 5

4 main projection sites for DA neuronal axons.

Answer 5

1. Striatum (caudate, putamen)
2. Limbic Cortex
3. Nucleus Accumbens
4. Prefrontal Cortex

Question 6

Name the 3 main DA pathways and disorders associated with them.

Answer 6

1. Nigrostriatal: SN to Striatum - too little DA leads to Parkinson’s
2. Mesolimbic: VTA to Cingulate Cortex and Nucleus Accumbens - too much DA leads to Schizophrenia

Mesocortical: VTA and SN to prefrontal cortex - too much DA leads to Schizophrenia and too little DA leads to Parkinson’s

Question 7

Name the biochemical pathway for DA synthesis.

Answer 7

Phenylalanine
Phenylalanine Hydroxylase
Tyrosine
Tyrosine Hydroxylase
L-Dopa
Dopa Decarboxylase
Dopamine

Question 8

Dopa decarboxylase inhibitor given with L-dopa for treatment of Parkinson’s.

Answer 8

Carbidopa

Question 9

Drug taken for hypertension that inhibits DA uptake into vesicles resulting in Parkinsonian Like symptoms when taken in high amounts.

Answer 9

Reserpine

Question 10

Describe the degredation metabolism for dopamine.

Answer 10

DA
              Monoamine Oxidase (MAO)
DOPAL
              Aldehyde Dehydrogenase
DOPAC
              Catechol-O-Methyltransferase (COMT)

Homovanillic Acid (HVA)

Question 11

Name 2 MAOIs, 2 COMT-Is, and 1 DA receptor agonist.

Answer 11

MAOIs

1. Deprenyl
2. Selegiline

COMT-Is

1. Tolcapone
2. Entacapone

DA-R agonist
Bromocriptine

MAOIs and COMT-Is mainly used for depression but can be used for Parkinson’s.

Bromocriptine is mainly used for Galactorrhea

Question 12

What is the reason for the “crash” experienced by cocaine addicts?

Answer 12

Most DA that is secreted from an axon terminal is recycled to make more DA. Cocaine inhibits DA-reuptake transporters and the presynaptic neuron is unable to produce adequate amounts of dopamine. The dopamine that remains out in the cleft eventually is polymerized to melanin.

Question 13

Why were Anti-cholinergics used to treat Parkinson’s disease?

Answer 13

DA and ACh balance each other in the brain. Decrease in DA leads to increased sensitivity to ACh.

Mechanism for tremors in Parkinson’s Disease

Question 14

Insecticide that is structurally similar to MPP+ and could lead to Parkinson’s if ingested in high amounts.

Answer 14

Paraquat