Synthesis of Biologically Important Compounds from Amino Acids

Synthesis of Biologically Important Compounds from Amino Acids

Synthesis of Biologically Important Compounds from Amino Acids

On this page

Heme Synthesis (from Glycine) - Bloody Building Blocks

  • Initial Step (Mitochondria):
    • $Glycine + Succinyl CoA \xrightarrow{ALA Synthase, PLP} \delta-Aminolevulinate (ALA) + CO_2 + CoA$.
    • Rate-limiting: ALA Synthase (PLP-dependent).
  • Pathway Overview & Key Intermediates:
-   Intermediates: ALA, Porphobilinogen, Uroporphyrinogen, Coproporphyrinogen, Protoporphyrinogen, Protoporphyrin IX.
  • Key Deficiencies:
    • ALA Dehydratase (Lead sensitive): ↑ ALA.
    • Uroporphyrinogen I Synthase: Acute Intermittent Porphyria (AIP). ↑ PBG, ALA. No photosensitivity.
  • Regulation:
    • Heme/Hemin: Feedback inhibits ALA synthase.
    • Glucose: Represses ALA synthase.
  • 📌 Porphyria (5 Ps): Painful abdomen, Polyneuropathy, Psychological issues, Precipitated by drugs, Purple pee.

⭐ Lead poisoning inhibits ALA dehydratase & Ferrochelatase → ↑ ALA & ↑ Protoporphyrin IX. Causes anemia, neurotoxicity.

Heme synthesis pathway and utilization

Tyrosine Derivatives - Mood & Pigment Power

Tyrosine, a non-essential amino acid (conditionally essential in PKU), is a precursor to vital catecholamines, melanin, and thyroid hormones.

  • Catecholamine Synthesis Pathway:

    ⭐ Tyrosine hydroxylase is the rate-limiting enzyme in catecholamine synthesis and requires tetrahydrobiopterin (THB or BH4) as a cofactor.

  • Melanin Synthesis (Pigment):

    • Tyrosine $\xrightarrow{\text{Tyrosinase (Cu-dependent)}}$ L-DOPA $\rightarrow$ Dopaquinone $\rightarrow$ Melanin.
  • Thyroid Hormones (T3/T4): Synthesized from iodination and coupling of tyrosine residues in thyroglobulin.

  • Clinical Significance:

    • Parkinson's Disease: ↓ Dopamine.
    • Pheochromocytoma: ↑ Catecholamines.
    • Albinism: Tyrosinase deficiency $\rightarrow$ ↓ Melanin.
    • Phenylketonuria (PKU): Phenylalanine Hydroxylase deficiency makes Tyrosine essential.

Tyrosine metabolism pathways and related disorders

Tryptophan Derivatives - Serene Nights & Energy

  • Key Products: Serotonin (neurotransmitter), Melatonin (sleep hormone), Niacin (Vitamin B3).
  • Serotonin (5-HT): Tryptophan $\xrightarrow{\text{Tryptophan hydroxylase (THB, rate-limiting)}}$ 5-Hydroxytryptophan $\xrightarrow{\text{Decarboxylase (PLP)}}$ Serotonin.
  • Melatonin: Serotonin $\xrightarrow{\text{Pineal gland, Acetylation, Methylation (SAM)}}$ Melatonin.
  • Niacin (B3): Tryptophan $\xrightarrow{\text{Kynurenine pathway (PLP, FAD, Niacin)}}$ Quinolinic acid $\rightarrow$ NAD+/NADP+. Inefficient.
  • Clinical Notes:
    • Depression (↓Serotonin; SSRIs target reuptake).
    • Sleep disorders (↓Melatonin).
    • Pellagra (Niacin deficiency): 📌 3 D's: Diarrhea, Dermatitis, Dementia (+ Death).
    • Hartnup disease (defective Tryptophan absorption).
    • Carcinoid syndrome (↑Serotonin).

⭐ Tryptophan is a precursor for serotonin, melatonin, and niacin (Vitamin B3); approximately 60 mg of tryptophan yields 1 mg of niacin.

Tryptophan metabolism pathways

Other AA Derivatives - Vital Variety Pack

  • Histamine: Histidine $\rightarrow$ Histamine (Histidine decarboxylase, PLP).
    • Sources: Mast cells, basophils.
    • Functions: Allergic reactions, gastric acid secretion.
  • GABA ($\ ext{gamma}$-Aminobutyric acid): Glutamate $\rightarrow$ GABA (Glutamate decarboxylase, PLP).
    • Function: Major inhibitory CNS neurotransmitter.
  • Creatine/Phosphocreatine:
    • Synthesis: Arginine + Glycine $\rightarrow$ Guanidinoacetate (kidney); Guanidinoacetate + SAM $\rightarrow$ Creatine (liver).
    • Storage: Creatine $\rightarrow$ Phosphocreatine (muscle, brain energy reserve).
    • Excretion: Creatinine (from non-enzymatic cyclization of creatine phosphate).
  • Glutathione (GSH): Glutamate + Cysteine $\rightarrow$ $\gamma$-Glutamylcysteine; then + Glycine $\rightarrow$ GSH.

    ⭐ Glutathione (GSH), a tripeptide of glutamate, cysteine, and glycine, is a major intracellular antioxidant, protecting cells from oxidative damage.

  • Nitric Oxide (NO): Arginine $\rightarrow$ NO + Citrulline (NO synthase; requires NADPH, THB).
    • Functions: Vasodilator, neurotransmitter. Bioactive molecules from amino acids

High‑Yield Points - ⚡ Biggest Takeaways

  • Tyrosine is a precursor for catecholamines (Dopamine, Epinephrine), thyroid hormones, and melanin.
  • Tryptophan forms serotonin, melatonin, and is a source for niacin (B3).
  • Glycine is essential for heme, purine rings, and creatine synthesis.
  • Arginine synthesizes nitric oxide (NO), urea, and creatine.
  • Histidine is decarboxylated to histamine, a key inflammatory mediator.
  • Glutamate is converted to GABA (inhibitory neurotransmitter) and glutathione.
  • S-Adenosylmethionine (SAM) from methionine is the primary methyl donor.

Practice Questions: Synthesis of Biologically Important Compounds from Amino Acids

Test your understanding with these related questions

Acute intermittent porphyria is due to deficiency of?

1 of 5

Flashcards: Synthesis of Biologically Important Compounds from Amino Acids

1/10

Creatine is synthesized from _____, arginine, and methionine (GAM)

TAP TO REVEAL ANSWER

Creatine is synthesized from _____, arginine, and methionine (GAM)

glycine

browseSpaceflip

Enjoying this lesson?

Get full access to all lessons, practice questions, and more.

Start Your Free Trial