Amino acids specialized products

Question 1

Catelcholamine synthesis rate limiting enzyme

Answer 1

• Tyrosine hydroxylase
• Converts Tyr -> 3,4 dihydroxy-phenylalanine (DOPA)
  *

Question 2

Catecholamine degradation

Answer 2

• NE & E degraded by 2 pathways leading to production VMA & other products
  
  • MAO: outer mitochondrial membrane
  • COMT: cytosolic; requires SAM
• DA also degraded by MAO & COMT producing HVA

Question 3

5-HT synthesis

Answer 3

• Hydroxylation of indole group of side chain of Trp
  
  • requires BH4
• Decarboxylation of alpha-carboxyl group
  
  • requires PLP

Question 4

5-HT degradation

Answer 4

• MAO-A: conversion of 5-HT -> N-acetyl 5-HT
• 2nd conversion: 5-hydroxyindole-acetaldehyde -> 5-HIAA
  
  • requires NAD+

Question 5

Melatonin synthesis

Answer 5

• acetylation & methylation of 5-HT
• requires Acetyl-CoA & SAM; donors of acetyl & methyl groups

Question 6

GABA synthesis

Answer 6

• Glutamate Decarboxylase: Glutamate -> GABA
  
  • PLP required

Question 7

Histidine synthesis

Answer 7

• Histidine Decarboxylase: decarboxylation of alpha-carboxyl group of histidine to produce Histamine
  
  • PLP required
• Histamine degraded by 2 different pathways; tissue dependent
  
  • Peripheral tissue: Deamination followed by oxidation
  • Brain: methylation, deaminated then oxidised
• Anti-histamines: do not block synthesis or promote degradation
  
  • instead receptor blockers

Question 8

NO synthesis & degradation

Answer 8

• NOS: converts Arginine -> NO
  
  • requires NADPH & O2
  • enzyme contains FAD, FMN as cofactors & Haem
  • requires BH4
  • Citrulline produced as 2nd product
• NO -> cGMP pathway
• action of cGMP terminated by Phosphodiesterase 5
  
  • Sildenafil (Viagra) targets this
• Nitroglycerine used in MI Rx is converted ot NO
  
  • vasodilation of coronary blood vessels and improvement of blood flow to heart

Question 9

Creatine synthesis

Answer 9

• starts in kidney & continues in liver
• transported via blood to brain, heart & muscle where it is used
• Amidotransferase: converts Arg & Gly -> Guanidinoacetate
• Methyltransferase: converts Guanidinoacetate -> Creatine
  
  • requires SAM

Question 10

Glutathione

Answer 10

• GSH: tripeptide used in redox rxn
  
  • contains Glu, Cys, Gly
• Intracell reducing agent (anti-oxidant)
• Important for detox of toxic H2O2 especially in RBC
• Glutathione Peroxidase: H2O2 produced during O2 transport is reduced by GSH by this enzyme
• Glutathione Reductase: GSH reformed from GSSG by this enzyme
  
  • requires NADPH s e- source
  • NADPH produced by HMP
• Reductant for thiol groups of Cys
• Can be conjugated to drugs to make them more water soluble
• serves as cofactor for some enzymatic rxn
• serves as aid in rearrangement of protein disulphide bonds