Amino acids as precursors to molecules- Lecture 81 Flashcards
What are catecholamines?
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
Describe the synthesis of catecholamines.
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
What is dopamine?
important neurotransmitter in many areas of the brain (esp substantia niagra area)
What is Parkinson Disease?
neurodegenerative condition resulting from decreasing amounts of dopamine causing loss of motor control, gait, speech, and memory impairments
How do you treat Parkinson Disease?
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
What is norepi?
regulates metabolism, bp, blood flow,
What are the uses of amino acids?
synthesis of proteins, enzymes, peptide hormones
energy (–> TCA metabolites, pyruvate, ketones, NAD+, NADP+, creatine (P)
synthesis of many compounds
How is glutathioine (GSH) synthesized?
Glutamate + cysteine + ATP –> gamma Glu-Cys + ADP
via gamma glutamyl-cysteine synthetase
gamma Glu-Cys + Glycine + ATP –> glutathione (GSH) + ADP
via gluthione synthetase
What is the importance of GSH?
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)
Describe the synthesis of essential neurotransmitters from tryptophan.
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
What is serotonin?
important neurotransmitter that makes you “feel good” (eg. Prozac), and has vasoconstrictive properties (regulates bp)
What is melatonin?
important regulator of sleep, mood, appetite, good feeling, and light/dark cycles
important antioxidant
What is THB used for?
synthesis of tyrosine, catecholamines, and serotonin
Where do each of the steps of creatine synthesis occur?
first step in the kidney
second step in the liver
all subsequent steps in the brain, heart, and muscle
Describe the synthesis of creatine.
glycine + arginine –> guanidinoacetate
guanidinoacetate + SAM –> creatine + SAH
creatine + ATP < —- > creatine phosphate + ADP
via creatine phosphokinase (CPK/CK)
creatine phosphate –> creatine
How can creatine levels in the urine be clinically significant?
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)
What are the isoenzymes of CPK?
MM, BB, MB
Describe the amino acid decarboxylase reactions.
glutamate --> GABA via glutamate decarboxylase histidine --> histamine via histidine decarboxylase serine --> ethanolamine via serine decarboxylase ornithine --> putrescine --> spermine + spermidine via ornithine carboxylase
What is GABA?
major inhibitory neurotransmitter
What is histamine?
powerful vasodilator present during inflammation and allergic attacks
promote secretion of pepsin and HCl (important to digestion in the stomach)
What is the function of spermine and spermidine?
stabilize DNA especially during replication
Describe the production of nitric oxide.
L-arginine + NADPH + O2 –> L-citrulline + NADP+ + NO
via NO synthase
What are the functions of NO?
relax smooth muscle, prevent platelet aggregation, function as a neurotransmitter in brain, and mediate tumorieidal and bacterial actions of macrophages
