Understanding the synthesis of noradrenaline is essential for B.Pharm students studying pharmacology and medicinal chemistry. This concise introduction explains biosynthesis from L-tyrosine through L-DOPA and dopamine to noradrenaline, emphasizing key enzymes—tyrosine hydroxylase (rate-limiting), aromatic L-amino acid decarboxylase, and dopamine β-hydroxylase—plus cofactors (BH4, PLP, ascorbate, copper) and intracellular sites (cytosol and vesicular lumen). Clinical relevance covers enzyme inhibitors, vesicular uptake (VMAT), and metabolic clearance by MAO and COMT that alter drug responses. These focused points support exam preparation and practical drug-development concepts. Keywords include noradrenaline synthesis, dopamine β-hydroxylase, tyrosine hydroxylase, VMAT, MAO/COMT and pharmacological inhibitors to aid SEO and revision. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. What is the rate-limiting enzyme in the biosynthesis of noradrenaline?
- Tyrosine hydroxylase
- Aromatic L-amino acid decarboxylase
- Dopamine β-hydroxylase
- Monoamine oxidase
Correct Answer: Tyrosine hydroxylase
Q2. What is the initial amino acid precursor for noradrenaline biosynthesis?
- L-tryptophan
- L-tyrosine
- L-phenylalanine
- L-histidine
Correct Answer: L-tyrosine
Q3. Which compound is the immediate precursor to noradrenaline in the synthetic pathway?
- L-DOPA
- Dopamine
- Epinephrine
- Normetanephrine
Correct Answer: Dopamine
Q4. Which enzyme converts dopamine to noradrenaline?
- Dopamine β-hydroxylase
- Aromatic L-amino acid decarboxylase
- Tyrosine hydroxylase
- Catechol-O-methyltransferase
Correct Answer: Dopamine β-hydroxylase
Q5. Which cofactors are essential for dopamine β-hydroxylase activity?
- Tetrahydrobiopterin and PLP
- Ascorbate and copper
- FAD and FMN
- Biotin and NAD+
Correct Answer: Ascorbate and copper
Q6. Where is dopamine β-hydroxylase primarily located within noradrenergic neurons?
- Vesicular lumen (storage vesicles)
- Mitochondrial matrix
- Postsynaptic membrane
- Nucleus
Correct Answer: Vesicular lumen (storage vesicles)
Q7. Which enzyme catalyzes the conversion of L-tyrosine to L-DOPA?
- Tyrosine hydroxylase
- Aromatic L-amino acid decarboxylase
- Phenylalanine hydroxylase
- Catechol-O-methyltransferase
Correct Answer: Tyrosine hydroxylase
Q8. Which cofactor is required by tyrosine hydroxylase for hydroxylation of tyrosine?
- Pyridoxal phosphate (PLP)
- Tetrahydrobiopterin (BH4)
- Biotin
- Thiamine pyrophosphate
Correct Answer: Tetrahydrobiopterin (BH4)
Q9. Aromatic L-amino acid decarboxylase (AADC) requires which vitamin-derived cofactor?
- Vitamin C
- Pyridoxal phosphate (PLP)
- Riboflavin
- Nicotinamide
Correct Answer: Pyridoxal phosphate (PLP)
Q10. Which transporter loads dopamine into synaptic vesicles for conversion to noradrenaline?
- DAT (dopamine transporter)
- NET (norepinephrine transporter)
- VMAT (vesicular monoamine transporter)
- OCT (organic cation transporter)
Correct Answer: VMAT (vesicular monoamine transporter)
Q11. Which pharmacological agent inhibits VMAT and depletes vesicular noradrenaline?
- Reserpine
- Cocaine
- Propranolol
Correct Answer: Reserpine
Q12. Which two enzymes are primarily responsible for metabolic degradation of noradrenaline?
- MAO and COMT
- DBH and TH
- AADC and PNMT
- Acetylcholinesterase and butyrylcholinesterase
Correct Answer: MAO and COMT
Q13. Which monoamine oxidase isoform preferentially metabolizes noradrenaline?
- MAO-A
- MAO-B
- Both isoforms equally
- Neither; COMT metabolizes exclusively
Correct Answer: MAO-A
Q14. Where is catechol-O-methyltransferase (COMT) activity commonly found?
- Only in synaptic vesicles
- In cytosol and membrane-associated forms, abundant in liver and brain
- Only in mitochondria
- Exclusively in the adrenal medulla chromaffin granules
Correct Answer: In cytosol and membrane-associated forms, abundant in liver and brain
Q15. Which drug is known to inhibit dopamine β-hydroxylase?
- Metyrosine (α-methyltyrosine)
- Disulfiram
- Carbidopa
- Selegiline
Correct Answer: Disulfiram
Q16. Which compound is a known inhibitor of tyrosine hydroxylase used experimentally and clinically?
- Metyrosine (α-methyltyrosine)
- Carbidopa
- Reserpine
- Entacapone
Correct Answer: Metyrosine (α-methyltyrosine)
Q17. Which peripheral decarboxylase inhibitor is co-administered with L-DOPA to prevent peripheral conversion to dopamine?
- Carbidopa
- Selegiline
- Entacapone
- Amantadine
Correct Answer: Carbidopa
Q18. Which substance acts as an electron donor (reducing agent) for DBH catalysis?
- Ascorbate (vitamin C)
- Glutathione
- FADH2
- NADPH
Correct Answer: Ascorbate (vitamin C)
Q19. In which tissue is noradrenaline converted to adrenaline by phenylethanolamine N-methyltransferase (PNMT)?
- Adrenal medulla (chromaffin cells)
- Sympathetic ganglia
- Vascular endothelium
- Liver hepatocytes
Correct Answer: Adrenal medulla (chromaffin cells)
Q20. What methyl donor cofactor is required by PNMT to form adrenaline from noradrenaline?
- S-adenosylmethionine (SAM)
- Tetrahydrofolate (THF)
- Acetyl-CoA
- Glutathione
Correct Answer: S-adenosylmethionine (SAM)
Q21. Which VMAT isoform predominates in central nervous system neurons?
- VMAT1
- VMAT2
- VMAT3
- VMAT4
Correct Answer: VMAT2
Q22. What is the effect of amphetamines on noradrenaline handling?
- Block MAO to prevent degradation
- Inhibit PNMT to block adrenaline formation
- Promote release of noradrenaline from presynaptic terminals
- Enhance COMT-mediated metabolism
Correct Answer: Promote release of noradrenaline from presynaptic terminals
Q23. Which enzymatic product results from COMT acting on noradrenaline?
- Normetanephrine
- Homovanillic acid
- 3,4-Dihydroxyphenylacetic acid (DOPAC)
- 5-Hydroxyindoleacetic acid (5-HIAA)
Correct Answer: Normetanephrine
Q24. Inhibition of monoamine oxidase (MAO) will generally cause what effect on noradrenaline levels?
- Decrease noradrenaline levels
- Increase noradrenaline levels
- No change in noradrenaline levels
- Convert noradrenaline to dopamine
Correct Answer: Increase noradrenaline levels
Q25. How is tyrosine hydroxylase activity commonly regulated in neurons?
- Allosteric inhibition by dopamine only
- Phosphorylation by protein kinases increases activity
- Irreversible proteolytic cleavage
- Sequestration into lysosomes
Correct Answer: Phosphorylation by protein kinases increases activity
Q26. A deficiency of tetrahydrobiopterin (BH4) will most directly reduce synthesis of which neurotransmitters?
- GABA and glycine
- Catecholamines (dopamine, noradrenaline) and serotonin
- Acetylcholine only
- Histamine only
Correct Answer: Catecholamines (dopamine, noradrenaline) and serotonin
Q27. Which enzyme is located inside the lumen of secretory vesicles rather than in the cytosol?
- Tyrosine hydroxylase
- Dopamine β-hydroxylase
- Tyrosine aminotransferase
- Catechol-O-methyltransferase
Correct Answer: Dopamine β-hydroxylase
Q28. Which vitamin deficiency impairs dopamine β-hydroxylase function and noradrenaline synthesis?
- Vitamin B12 deficiency
- Vitamin C (ascorbic acid) deficiency
- Vitamin D deficiency
- Vitamin K deficiency
Correct Answer: Vitamin C (ascorbic acid) deficiency
Q29. Which cofactor is essential for aromatic L-amino acid decarboxylase activity?
- Folate
- Pyridoxal phosphate (PLP)
- Vitamin E
- Vitamin K
Correct Answer: Pyridoxal phosphate (PLP)
Q30. Which analytical technique is commonly used to quantify noradrenaline in biological samples?
- HPLC with electrochemical detection
- ELISA for acetylcholine
- Western blot for tyrosine hydroxylase
- Gram staining
Correct Answer: HPLC with electrochemical detection
Q31. Which amino acid is converted to tyrosine by phenylalanine hydroxylase?
- L-tryptophan
- L-phenylalanine
- L-leucine
- L-methionine
Correct Answer: L-phenylalanine
Q32. Phenylalanine hydroxylase requires which cofactor that is also used by tyrosine hydroxylase?
- Tetrahydrobiopterin (BH4)
- Pyridoxal phosphate (PLP)
- Biotin
- NAD+
Correct Answer: Tetrahydrobiopterin (BH4)
Q33. Which of the following is NOT a catecholamine?
- Dopamine
- Noradrenaline
- Epinephrine
- Serotonin
Correct Answer: Serotonin
Q34. The conversion of dopamine to noradrenaline by DBH requires which gaseous reactant?
- Nitrogen
- Oxygen
- Carbon dioxide
- Hydrogen sulfide
Correct Answer: Oxygen
Q35. In sympathetic neurons, where is the rate-limiting enzyme tyrosine hydroxylase primarily localized?
- Synaptic vesicle lumen
- Presynaptic cytosol near nerve terminal
- Postsynaptic membrane
- Sarcomere
Correct Answer: Presynaptic cytosol near nerve terminal
Q36. Which drug class increases synaptic noradrenaline by blocking reuptake transporter NET?
- Tricyclic antidepressants and some SNRIs
- MAO inhibitors only
- Beta blockers
- Calcium channel blockers
Correct Answer: Tricyclic antidepressants and some SNRIs
Q37. Which effect would you expect from cocaine on noradrenaline synaptic levels?
- Decrease by enhancing MAO activity
- Increase by inhibiting NET (norepinephrine transporter)
- Convert noradrenaline to adrenaline
- Stimulate VMAT to increase vesicular uptake
Correct Answer: Increase by inhibiting NET (norepinephrine transporter)
Q38. The norepinephrine transporter (NET) is located on which membrane?
- Presynaptic plasma membrane
- Postsynaptic nuclear membrane
- Golgi apparatus membrane
- Mitochondrial inner membrane
Correct Answer: Presynaptic plasma membrane
Q39. Which vitamin is directly involved as a cofactor in decarboxylation of L-DOPA to dopamine?
- Vitamin B6 (as PLP)
- Vitamin B12
- Vitamin C
- Vitamin A
Correct Answer: Vitamin B6 (as PLP)
Q40. What is the product formed immediately after tyrosine hydroxylation?
- Dopamine
- L-DOPA
- Noradrenaline
- Adrenaline
Correct Answer: L-DOPA
Q41. Which irreversible inhibitor depletes vesicular monoamines by blocking VMAT?
- Reserpine
- Carbidopa
- Entacapone
- Metyrosine
Correct Answer: Reserpine
Q42. Which MAO isoform is primarily targeted by selegiline at low doses?
- MAO-A
- MAO-B
- Both MAO-A and MAO-B equally
- Neither; selegiline targets COMT
Correct Answer: MAO-B
Q43. COMT uses which molecule as the methyl donor for catecholamine methylation?
- Acetyl-CoA
- S-adenosylmethionine (SAM)
- UDP-glucuronic acid
- ATP
Correct Answer: S-adenosylmethionine (SAM)
Q44. Excess production of noradrenaline is a hallmark of which tumor?
- Pheochromocytoma
- Glioblastoma
- Hepatocellular carcinoma
- Benign prostatic hyperplasia
Correct Answer: Pheochromocytoma
Q45. The gene symbol commonly used for tyrosine hydroxylase is:
- TH
- TYRH
- DBH
- PNMT
Correct Answer: TH
Q46. Congenital deficiency of dopamine β-hydroxylase typically results in which clinical feature?
- Hypertension and tachycardia
- Orthostatic hypotension and low plasma norepinephrine
- Excessive sweating and hyperthermia
- Hyperpigmentation
Correct Answer: Orthostatic hypotension and low plasma norepinephrine
Q47. Which metabolite is a major breakdown product of central noradrenaline used as a biomarker?
- 3-Methoxy-4-hydroxyphenylglycol (MHPG)
- Homovanillic acid (HVA)
- 5-Hydroxyindoleacetic acid (5-HIAA)
- Vanillylmandelic acid (VMA) only
Correct Answer: 3-Methoxy-4-hydroxyphenylglycol (MHPG)
Q48. Which metal ion is critical for optimal activity of dopamine β-hydroxylase?
- Iron (Fe2+)
- Copper (Cu2+)
- Zinc (Zn2+)
- Manganese (Mn2+)
Correct Answer: Copper (Cu2+)
Q49. Which compound is the major methylated metabolite of noradrenaline formed by COMT?
- Normetanephrine
- Metanephrine
- Vanillylmandelic acid (VMA)
- Homovanillic acid (HVA)
Correct Answer: Normetanephrine
Q50. Carbidopa inhibits which enzyme in the noradrenaline synthetic pathway?
- Tyrosine hydroxylase
- Aromatic L-amino acid decarboxylase (AADC)
- Dopamine β-hydroxylase
- Catechol-O-methyltransferase (COMT)
Correct Answer: Aromatic L-amino acid decarboxylase (AADC)
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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