6.2 BCHM - Dopamine Biochem Flashcards
What are monoamine transmitters (describe their structure)?
Contain nitrogen atom (amine) and connected to an aromatic group through a 2 carbon chain.
Are monoamine neurotransmitters ionotropic or metabotropic? hypothesize why that is?
Metabotropic.
They are large (cost a lot to make), therefore make them last (long lasting).
Serotonin and catecholamine neurotransmitters are created in very similar biosynthetic pathways. What are they?
Tyrosine —(tyrosine hydroxylase)–> DOPA (dihydroxyphenylalanine) —-(DOPA decarboxylase)–> dopamine
Tryptophan –(tryptophan hydroxylase)–> 5-hydroxytryptophan –(5-hydroxytryptophan decarboxylase)–> 5-hydroxytryptamine (serotonin)
What cofactor do hydroxylase enzymes require? What does it do?
Tetrahydrobiopterin.
Activates oxygen molecule in order to release activated oxygen atom to attack and oxidize various compounds.
Neurons that use norepinephrine need on more step to convert dopamine -> norepinephrine, what is that step (name enzyme)? What is the next step to convert norepinephrine -> epinephrine?
Dopamine –(dopamine hydroxylase)–> norepinephrine –(phenylethanoamine-N-mythyl-transferase)–> epinephrine
which step in this process is the rate limiting step?
The first step.
Where does the synthesis of monoamine neurotransmitters occur? How about the breakdown (broken down with what)?
Biosynthesis of monoamine neurotransmitters occurs in presynaptic neurons.
Degradation occurs in presynaptic neurons and astrocytes using monoamine oxidases.
Where does the tyrosine precursor used in Dopamine biosynthesis come from, how do any of these amino acids get into the brain for that matter?!
Large Neutral Amino Acid Transporter - transports large hydrophobic amino acids through BBB.
Where do humans get tryptophan and phenylalanine? What is the result of this ^ on the concentration of different neurotransmitters?
These are essential amino acids, cannot be made by humans and must be taken in from diet.
Due to this fact, the concentration of neurotransmitters such as serotonin, dopamin, norepinephrine, and epinephrine vary greatly on the diet.
How is tyrosine formed from phenylalanine? (enzyme, where made?). What would the result be of loss of this enzyme?
Oxidization of phenylalanine in the liver => tyrosine.
Phenylalanine hydroxylase.
Phenylketourea (PKU) would occur (autosomal recessive) -> depletion of tyrosine and buildup of phenylalanine.
Some of the phenylalanine would be alternatively metabolized and transaminated to form phenylpyruvate.
Due to the fact that phenylalanine has the lowest Km of any large hydrophobic amino acid what are the results of PKU and why?
in PKU transport of tyrosine and other large hydrophobic amino acids into brain is restricted.
Depletion of tyrosine and tryptophan in brain can reduce production of neurotransmitters.
Restriction of amino acids interferes with protein synthesis and brain development, especially during child development.
Extreme levels of phenyalanine are believed to be toxic.
What are some treatments of PKU? How do they work?
Modified diets.
Some cases respond to tetrahydrobiopterin.
Tetrahydrobiopterin: cofactor for phenylalanine hydroxylase. activates O2 for hydroxylase. Some PKU cases are caused by mutation in this cofactor.
What if a pt. has a direct mutation in phenylalanine hydroxylase, will tetrahydrobiopterin work, why why not?
Yes.
This tightly binding ligand can act as a chaperone and help the mutated protein fold correctly.
Why do most pts. with PKU have blonde hair and blue eyes?
They lack melanin.
Dark pigment in hair and eyes, built modularly from dopa building blocks, which are in turn made form tyrosine which is made from phenylalanine.
What is Parkinson’s Disease a result of? how is it treated?
Result from inadequate dopamine signaling from substantia nigra.
Treat with L-DOPA. (levodopa)
