Pharmacy Stage 3: Amino Acids Conversion

Conversion of Amino Acids to Specialized Products

• Certain proteins contain amino acids that have been post-translationally modified to perform specific functions.
• Hydroxylation of lysine to 5-hydroxylysine stabilizes maturing collagen fibers.

Importance of Amino Acids

• Amino acids serve as precursors of diverse biologic materials.
• Examples of biological molecules derived from amino acids include:
  • Creatine and creatinine
  • Catecholamines
  • Serotonin and melatonin
  • Histamine
  • Glutathione (GSH)
  • Purine and pyrimidine rings

Creatine and Creatinine

• Creatine is stored in the muscle in the form of creatine phosphate, which acts as an energy store.
• Creatinine is formed in muscle from creatine phosphate by irreversible, non-enzymatic dehydration, and loss of phosphate (used for muscle contraction).
• The amount of creatinine produced is constant from day to day and depends on muscle mass.
• Creatinine is excreted in urine.

Catecholamines

• The name catechol refers to the dihydroxylated phenyl ring.
• The amine derivatives of catechol are called catecholamines.
• Tyrosine is the precursor for the synthesis of catecholamines, namely:
  • Dopamine
  • Norepinephrine (noradrenaline)
  • Epinephrine (adrenaline)
• Conversion of tyrosine to catecholamines occurs in adrenal medulla and central nervous system.
• Enzymes involved in catecholamine synthesis:
  • Tyrosine hydroxylase
  • Aromatic amino acid decarboxylase
  • Dopamine β-hydroxylase
  • Phenylethanolamine N-methyltransferase
• Catecholamines regulate carbohydrate and lipid metabolisms, stimulate the degradation of triacylglycerol and glycogen, and cause an increase in blood pressure.
• Dopamine and norepinephrine serve as neurotransmitters in the brain and autonomous nervous system.

Serotonin and Melatonin

• Serotonin (5-hydroxytryptamine, 5HT) is a neurotransmitter synthesized from tryptophan.
• Enzymes involved in serotonin synthesis:
  • Tryptophan hydroxylase
  • Aromatic amino acid decarboxylase
• Melatonin is a hormone, mostly synthesized by the pineal gland.
• Serotonin is acted upon by serotonin N-acetylase to give N-acetylserotonin, which undergoes O-methylation to produce melatonin.
• Synthesis and secretion of melatonin from pineal gland is controlled by light.

Histamine

• Histamine is a biogenic amine that functions in allergic reactions and gastric acid secretion.
• Histamine is formed by decarboxylation of histidine, catalyzed by pyridoxal phosphate-dependent enzyme histidine decarboxylase.
• Histamine is present in all tissues.

Glutathione (GSH)

• Glutathione is γ-Glutamyl cysteinyl glycine.
• The active part is the -SH group of cysteine (sulfhydryl group).
• Biosynthetic reactions of GSH are catalyzed by γ-glutamyl cysteine synthetase and GSH synthetase.