Amino acids as precursors to molecules- Lecture 81

Question 1

What are catecholamines?

Answer 1

norepinephrine, DOPA, dopanine, and epinephrine
synthesized in the brain and adrenals to function as neurotransmitters and regulators of blood flow, blood pressure, metabolism, and energy production

Question 2

Describe the synthesis of catecholamines.

Answer 2

L-tyrosine –> L-DOPA
via tyrosine hydroxylase (TH) with O2 and tetrahydrobiopterin cofactors
L-DOPA –> Dopamine
via L-aromatic amino acid decarboxylase (AAAD)/”DOPA decarboxylase”
Dopamine –> norepinephrine/L-noradrenaline
via dopamine-beta-hydroxylase (DBH) with ascorbate, Cu2+, and O2 cofactors
borepinephrine/L-noradrenaline –> epinephrine/L-adrenaline
via phenylethanolamine-N-methyltransferase (PNMT) with SAM cofactor

Question 3

What is dopamine?

Answer 3

important neurotransmitter in many areas of the brain (esp substantia niagra area)

Question 4

What is Parkinson Disease?

Answer 4

neurodegenerative condition resulting from decreasing amounts of dopamine causing loss of motor control, gait, speech, and memory impairments

Question 5

How do you treat Parkinson Disease?

Answer 5

give DOPA as treatment (because it is neutral at body pH and can cross blood-brain barrier whereas dopamine cannot because it is positive)
pts progressively become dopa resistant the longer they are on medication

Question 6

What is norepi?

Answer 6

regulates metabolism, bp, blood flow,

Question 7

What are the uses of amino acids?

Answer 7

synthesis of proteins, enzymes, peptide hormones
energy (–> TCA metabolites, pyruvate, ketones, NAD+, NADP+, creatine (P)
synthesis of many compounds

Question 8

How is glutathioine (GSH) synthesized?

Answer 8

Glutamate + cysteine + ATP –> gamma Glu-Cys + ADP
via gamma glutamyl-cysteine synthetase
gamma Glu-Cys + Glycine + ATP –> glutathione (GSH) + ADP
via gluthione synthetase

Question 9

What is the importance of GSH?

Answer 9

most important cellular antioxidant
important in cellular redox control helping to maintain sulfhydryl-disulfide equilibrium
detoxifying agent removing many xenobiotics by conjugation reactions (forms more soluble xenobiotic-GSH conjugates that are excreted)
play a role in amino acid entry into the cells (some cells- relationship unclear)

Question 10

Describe the synthesis of essential neurotransmitters from tryptophan.

Answer 10

tryptophan + O2 + TBH –> 5-hydroxytryptophan
via tryptophan hydroxylase
5-hydroxytryptophan –> serotonin + CO2
via L-aromatic amino decarboxylase with PLP cofactor
serotonin + acetyl CoA –> N-acetyl serotonin + CoASH
N-acetyl serotonin + SAM –> Melatonin + SAH

Question 11

What is serotonin?

Answer 11

important neurotransmitter that makes you “feel good” (eg. Prozac), and has vasoconstrictive properties (regulates bp)

Question 12

What is melatonin?

Answer 12

important regulator of sleep, mood, appetite, good feeling, and light/dark cycles
important antioxidant

Question 13

What is THB used for?

Answer 13

synthesis of tyrosine, catecholamines, and serotonin

Question 14

Where do each of the steps of creatine synthesis occur?

Answer 14

first step in the kidney
second step in the liver
all subsequent steps in the brain, heart, and muscle

Question 15

Describe the synthesis of creatine.

Answer 15

glycine + arginine –> guanidinoacetate
guanidinoacetate + SAM –> creatine + SAH
creatine + ATP < —- > creatine phosphate + ADP
via creatine phosphokinase (CPK/CK)
creatine phosphate –> creatine

Question 16

How can creatine levels in the urine be clinically significant?

Answer 16

amount of creatine excreted is proportional to the total creatine phosphate content of the body (used to estimate muscle mass)
amount of creatine excreted indicates the amount of muscle breakdown (high levels indicates kidney injury)

Question 17

What are the isoenzymes of CPK?

Answer 17

MM, BB, MB

Question 18

Describe the amino acid decarboxylase reactions.

Answer 18

glutamate --> GABA
via glutamate decarboxylase
histidine --> histamine
via histidine decarboxylase
serine --> ethanolamine
via serine decarboxylase
ornithine --> putrescine --> spermine + spermidine
via ornithine carboxylase

Question 19

What is GABA?

Answer 19

major inhibitory neurotransmitter

Question 20

What is histamine?

Answer 20

powerful vasodilator present during inflammation and allergic attacks
promote secretion of pepsin and HCl (important to digestion in the stomach)

Question 21

What is the function of spermine and spermidine?

Answer 21

stabilize DNA especially during replication

Question 22

Describe the production of nitric oxide.

Answer 22

L-arginine + NADPH + O2 –> L-citrulline + NADP+ + NO

via NO synthase

Question 23

What are the functions of NO?

Answer 23

relax smooth muscle, prevent platelet aggregation, function as a neurotransmitter in brain, and mediate tumorieidal and bacterial actions of macrophages