Lecture 9 (Part 1): Amino Acids as Biosynthetic Precursors

what amino acid is Tyrosine synthesized from?

phenylalanine

what enzyme catalyzes tyrosine synthesis from phenylalanine?

phenylalanine (Phe) hydroxylase

Phe hydroxylase synthesizes ________ using phenylalanine, ____ and _____

tyrosine; NADH, O2

what does Phe Hydroxylase do to make tyrosine from phenylalanine?

add hydroxy group to benzene ring

what molecule is made from tyrosine by adding another hydroxyl group?

homogentistate

what molecule is this?

phenylalanine

what molecule is this?

tyrosine

how does homogentistate differ from tyrosine?

extra hydroxyl group

what molecule is this?

homogentistate

homogentistate is an intermediate in ___________

tyrosine degredation

homogentistate is broken down into _______ and _______ in tyrosine degradation

acetoacetate; fumarate

alkaptonuria is a disease caused by the inability to ____________

break down homogentistate

alkaptonuria leads to a build up of _______ in the urine

homogentistate

what enzyme deficiency causes alkaptonuria?

homogentistate 1,2-dioxygenase

what is the fumerate produced in tyrosine degradation use for?

TCA and gluconeogensis

what is phenylketonuria (PKU) caused by?

defect in phenylalanine hydroxylase

what happens when phenylalanine hydroxylase is deficient/defected?

build up of phenylalanine

what happens when phenylalanine builds up due to phenylketonuria?

amine is removed to make phenylpyruvate

what enzyme is used to remove an amino group to phenylalanine?

phenylalanine transaminase

what does phenyl pyruvate spontaneously turn into?

phenyl lactate

what is the ultimate result of phenylketonuria?

buildup of phenyl lactate and phenyl pyruvate

What amino acid is Dopamine synthesized from?

tyrosine

what amino acid is epinephrine synthesized from?

tyrosine (from dopamine)

what is the intermediate molecule between tyrosine and dopamine?

L-Dopa

what enzyme converts tyrosine to L-dopa?

tyrosine hydroxylase

what does tyrosine hydroxylase do?

add hydroxyl group to tyrosine

what enzyme synthesizes dopamine from L-Dopa?

Aromatic AA decarboxylase

what does Aromatic AA decarboxylase do?

remove CO2 from L-Dopa (to make dopamine)

what is the intermediate molecule between dopamine and epinephrine?

norepinephrine

what enzyme converts dopamine to norepinephrine?

dopamine B-hydroxylase

what does dopamine B-hydroxylase do?

add a hydroxyl group to dopamine

how is norepinephrine converted into epinephrine?

methylation of amino group

what enzyme converts norepinephrine into epinephrine?

Phenylethanolamine N-methyl transferase

what does phenylethanolamine N-methyl transferase do?

adds a methyl group to norepinephrine

what are the main types of catecholamines? (3)

dopamine, norepinephrine, epinephrine

dopamine, epinephrine, and norepinephrine are examples of:

catecholamines

what do catecholamines do in the body? (physiological response)

flight or fight response

Parkinson’s is accounted with a reduced levels of ________

dopamine

in the CNS, dopamine functions as a ____________

neurotransmitter

OUTSIDE the central nervous system (i.e. outside the brain) dopamine functions as a _________

chemical messenger

dopamine in the CNS is involved in _______, ________, and _________

motor control; reward-motivated behavior; hormone release

OUTSIDE the CNS, dopamine effects bodily functions such as ________, ________, __________, ________

blood pressure; kidney function; intestinal motility; insulin release

the cause of Parkinson’s disease is the loss of cells in the ____________ that produce __________

substantia nigra; neurotransmitters

what are patients given to treat Parkinson’s disease?

L-Dopa (levodopa) and carbidopa

Dopamine is __________ to pass through the blood brain barrier, while L-Dopa __________

unable; is able to

carbidopa is a drug that inhibits _________

aromatic AA decarboxylase

why administer L-dopa instead of dopamine?

it can pass through the blood brain barrier (dopamine cannot)

in order to treat Parkinson’s, you want high levels of _______ in the ________, but not in the ________

dopamine; brain; body

can carbidopa pass through the blood brain barrier?

no

can L-dopa pass through the blood brain barrier?

yes

can dopamine pass through the blood brain barrier?

no

why do you administer carbidopa with L-dopa to treat Parkinson’s?

keeps dopamine outside the brain at low levels

why do you want to keep dopamine levels outside the brain LOW? (via carbidopa)

prevents side effects

dopamine functions as a _________ in the brain and as a _________ in other tissue

neurotransmitter; chemical signal

what would happen if a patient was given L-Dopa WITHOUT carbidopa?

L-Dopa would form dopamine, build up in body and cause side effects

what cofactor does aromatic AA decarboxylase use?

PLP

what molecule is this?

L-dopa

what molecule is this?

dopamine

what molecule is this?

norepinephrine

what molecule is this?

epinephrine

what cofactor does Phenylethanolamine N-methyl transferase use?

SAM

how does carbidopa inhibit aromatic AA decarboxylase?

forms schiff base with PLP, gets stuck

what part of Carbidopa forms a schiff base with PLP?

hydrazine group (N-N bond)

why does carbidopa get stuck in PLP?

carbanion is not resonance stabilized (won’t leave)

carbdiops is a _______ inhibitor

suicide

what amino acid is GABA synthesized from?

glutamate

what amino acid is histamine synthesized from?

histidine

what enzyme forms GABA from glutamate?

glutamate decarboxylase

what enzymes forms histamine from histidine?

histidine decarboxylase

what molecule is this?

GABA

what molecule is this?

histamine

glutamate is the most common _______

neurotransmitter

GABA is an __________

inhibitory neurotransmitter

histamine is a ________ that stimulates an _______

vasodilator; allergic response

Benadryl aka _______

diphenhydramine

what is diphenhydramine?

inhibitor of histamine receptor

how does Benadryl help with allergies?

binds to receptor, prevents histamine binding

what molecule is this?

diphenhydramine

what molecule is serotonin synthesized from?

tryptophan

what is the intermediate molecule between tryptophan and serotonin?

5-hydroxy tryptophan

what enzyme converts tryptophan to 5-hydroxy tryptophan?

tryptophan hydroxylase

what enzyme converts 5-hydroxy tryptophan to serotonin?

aromatic amino acid decarboxylase

what does tryptophan hydroxylase do?

adds hydroxy group (to ring)

how is 5-hydroxy tryptophan converted into serotonin? (what happens)

decarboxylation

where is serotonin found? (3)

intestine, platelets, CNS

what is serotonin’s role in the intestine?

regulates gut movements

what is serotonin’s role in the platelets?

vasoconstrictor (helps blood clotting)

what is serotonin’s role in the CNS

mood, appetite, sleep

what do SSRIs do?

prevent uptake of serotonin in nerve synapse

SSRIs stand for:

selective-serotonin-re-uptake-inhibitors

______ are derived from glycine and succinyl-CoA?

porphyrins

porphyrins are derived from ______ and _______

glycine; succinyl-CoA

what cells are porphyrins synthesized?

liver and erythroid cells

what amino acid is heme made from?

glycine

what does the enzyme g-aminolevulinate synthase do?

form g-aminolevulinate from glycine and succinyl-CoA

how is g-aminolevulinate made from glycine and succinyl-CoA?

decarboxylation

what happens to g-aminolevulinate in porphyrin synthesis?

2 are combined to make porphobilinogen

what happens to porphobilinogen?

4 combined to make uroporphyrinogen III

what happens to uroporphyrinogen III to form heme?

add Fe and 6 decarboxylations

what is heme a major component of? (3)

hemoglobin, myoglobin, cytochromes