PMBC20 - Synthesis of specialized products from amino acids

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1

How is DOPA formed?

from tyrosine via the enzyme tyrosine hydroxylase (tetrahydrobiopterin coenzyme)

2

How is dopamine formed?

from DOPA via the enzyme DOPA decarboxylase (PLP vitamin B6 coenzyme) in the substantia nigra of the basal ganglia

3

How is norepinephrine formed?

from dopamine via the enzyme dopamine beta-hydroxylase (vitamin C coenzyme) in the sympathetic ganglia and adrenal medulla

4

How is epinephrine formed?

From norepinephrine via the enzyme phenylethanolamine N methyl transferase (PNMT) with methyl group donated by SAM in the adrenal medulla

5

Parkinson's disease

neurodegenerative disorder, loss of dopamine producing cells in the basal ganglia - treat with L-DOPA (dopamine can't cross blood-brain barrier) and DOPA decarboxylase inhibitors (don't want dopamine to be formed in peripheral tissues)

6

How are the catecholamines degraded?

By monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) to form vanillyl mandelic acid (VMA) which is excreted in the urine (can be measured to estimate production of catecholamines)

7

Pheochromocytoma

Overproduction of catecholamines due to a tumor of the adrenal medulla - episodic headache, sweating, tachycardia (stress related) - high urinary VMA and catecholamines

8

How is serotonin synthesized?

In the gut from tryptophan into 5 hydroxy tryptophan by the enzyme tryptophan hydroxylase (tetrahydrobiopterin coenzyme). 5-hydroxy tryptophan is converted to serotonin by amino acid decarboxylase. Serotonin is metabolized to 5-hydroxyindole acetic acid (5-HIAA) by MAO

9

Carcinoid syndrome

Tumor of APUD cells in GIT - increased production of SEROTONIN, increased 5-HIAA in urine, cutaneous flushing, diarrhea, bronchospasm

10

How is GABA synthesized?

Glutamate uses the enzyme glutamate decarboxylase and the coenzyme PLP (vitamin B6)

11

How is histamine synthesized?

produced during allergic reactions from histidine using the enzyme Amino acid decarboxylase and the coenzyme PLP (vitamin B6) - vasodilator

12

H1 blocker

antihistamine

13

H2 blocker

stomach ulcers

14

How is creatine synthesized?

From arginine, glycine and SAM

15

How is creatine excreted?

As creatinine in the urine

16

Serum creatinine

one of the best indicators of renal disease

17

How is nitric oxide synthesized?

From arginine by nitric oxide synthase (releases a citrulline) - vasodilator with a short half life - becomes cGMP via guanylyl cyclase

18

Nitroglycerin

used in treatment of myocardial ischemia (angina) - converted to NO and results in vasodilation of coronary blood vessels

19

Albinism

group of disorders deficient in TYROSINASE that converts tyrosine to melanin

20

Glutathione

glutamate, cysteine and glycine - antioxidant, important for detox of H2O2 especially in RBCs (Needs NADPH - G6PDH deficiency- drug induced hemolytic anemia - fava beans, primaquine)

21

Non-classical phenylalaninemia

problem with coenzyme tetrahydrobiopterin - either dihydrobiopterin reductase enzyme deficiency or problem with dihydrobiopterin synthesis - 3 reactions - phenylalanine hydroxylase (phenylalanine to tyrosine), tyrosine hydroxylase (tyrosine to DOPA), Tryptophan hydroxylase (tryptophan to 5-hydroxy tryptophan) - severe neurological problems - addition of dietary tetrahydrobiopterin and precursors of neurotransmitters and dietary restriction of phenylalanine