Vitamin B6 and Transamination

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Vitamin B6 Forms & Sources - Pyridoxine Powerhouse

  • Vitamers (3 forms):
    • Pyridoxine (PN): Plant origin.
    • Pyridoxal (PL).
    • Pyridoxamine (PM): Animal origin.
    • All convert to phosphate esters (PNP, PLP, PMP).
  • Active Coenzyme: Pyridoxal Phosphate (PLP).

    ⭐ Pyridoxal Phosphate (PLP) is the biologically active coenzyme form of Vitamin B6.

  • Vitamin B6 Vitamers and PLP Structures
  • Sources & RDA:
CategoryExamples
SourcesMeat, fish, poultry, whole grains, vegetables
RDA (Adults)1.3-1.7 mg/day

PLP Coenzyme Function - Amino Acid Ace

  • Pyridoxal Phosphate (PLP): B6's active coenzyme, vital for amino acid (AA) metabolism.
  • Mechanism: Schiff Base Cycle
    • Internal Aldimine: PLP's aldehyde group + enzyme's Lysine residue: $\text{E-CHO} + \text{H}_2\text{N-Lys} \rightleftharpoons \text{E-CH=N-Lys} + \text{H}_2\text{O}$.
    • External Aldimine: Incoming AA substrate displaces enzyme's Lysine: $\text{E-CH=N-Lys} + \text{R-CH(NH}_2\text{)-COOH} \rightleftharpoons \text{E-Lys-NH}_2 + \text{R-CH(COOH)-N=CH-PLP}$.
    • Labilizes AA $\alpha$-carbon bonds, enabling diverse reactions. PLP Schiff base formation in transamination
  • PLP-Dependent Reactions:
    • Transamination
    • Decarboxylation
    • Racemization
    • Deamination
    • Side-chain modifications

⭐ The aldehyde group of PLP is the reactive part, forming a Schiff base with amino groups.

Transamination Mechanism & Significance - Amino Group Shuffle

  • General Reaction: Transfer of an amino group ($ ext{-NH}_2$) from an amino acid to an $\alpha$-keto acid, yielding a new amino acid and a new $\alpha$-keto acid. $\text{Amino Acid}_1 + \alpha\text{-Keto Acid}_2 \rightleftharpoons \alpha\text{-Keto Acid}_1 + \text{Amino Acid}_2$

  • Mechanism: 'Ping-pong bi-bi' reaction. PLP (Pyridoxal Phosphate) is the coenzyme.

    • Enzyme-PLP + Amino Acid$_1$ $\rightarrow$ Enzyme-PMP + $\alpha$-Keto Acid$_1$. (PLP accepts $\text{-NH}_2$, forms PMP)
    • Enzyme-PMP + $\alpha$-Keto Acid$_2$ $\rightarrow$ Enzyme-PLP + Amino Acid$_2$. (PMP donates $\text{-NH}_2$, regenerates PLP) PLP-dependent transamination reaction mechanism
  • Key Transaminases (Aminotransferases):

    FeatureALT (Alanine Aminotransferase/SGPT)AST (Aspartate Aminotransferase/SGOT)
    ReactionAlanine + $\alpha$-KG $\rightleftharpoons$ Pyruvate + GlutamateAspartate + $\alpha$-KG $\rightleftharpoons$ OAA + Glutamate
    Tissue (Major)Liver (specific)Liver, Heart, Sk. Muscle, Kidney (Assorted)
    Clinical Sig.$\uparrow$ in liver damage (e.g., viral hepatitis)$\uparrow$ in liver/muscle damage, MI
    📌 Mnemonic: ALT for Liver; AST for Several Tissues (Heart, Liver, Muscle).
  • Metabolic Significance:

    • Funneling amino groups to glutamate (for urea cycle or AA synthesis).
    • Synthesis of non-essential amino acids.
    • Role in gluconeogenesis (e.g., alanine $\rightarrow$ pyruvate).
  • Flowchart: Ping-Pong Bi-Bi Mechanism

⭐ All transamination reactions require PLP, and glutamate is a common product, acting as a collector of amino groups for disposal or reuse.

Vitamin B6 Clinical Aspects - Deficiency & Drama

  • Deficiency Causes:
    • Dietary inadequacy, chronic alcoholism.
    • Drug interactions: 📌 "I Pee On Coins" (Isoniazid, Penicillamine, Oral Contraceptives, Cycloserine).
  • Deficiency Manifestations:
    • Skin: Seborrheic dermatitis-like rash, cheilosis, glossitis.
    • Neurological: Peripheral neuropathy, irritability; convulsions in infants (due to impaired GABA synthesis).
    • Hematological: Sideroblastic anemia (microcytic, hypochromic). *
    • Diagnosis: Tryptophan load test (↑ urinary xanthurenic acid).

⭐ Isoniazid, an anti-tubercular drug, can induce Vitamin B6 deficiency by forming an inactive hydrazone complex with pyridoxal phosphate (PLP), leading to its functional inactivation and increased excretion.

  • Toxicity:
    • Sensory neuropathy with chronic high doses (> 200 mg/day).
  • Therapeutic Uses:
    • Prevention of INH-induced neuropathy (prophylactic dose 10-25 mg/day).
    • Nausea and vomiting of pregnancy.
    • Homocystinuria (pharmacological doses).

High‑Yield Points - ⚡ Biggest Takeaways

  • Vitamin B6 active form is Pyridoxal Phosphate (PLP).
  • PLP is the key coenzyme for transamination reactions, crucial for amino acid metabolism.
  • Aminotransferases (e.g., ALT, AST) are PLP-dependent; their levels indicate liver damage.
  • Transamination involves transfer of an amino group from an amino acid to a keto acid.
  • B6 deficiency leads to peripheral neuropathy, sideroblastic anemia, dermatitis, and seizures.
  • Isoniazid can cause B6 deficiency by forming inactive complexes with PLP.
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Practice Questions: Vitamin B6 and Transamination

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Which amino acid is not involved in transamination?

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Severe deficiencies of vitamin _____ can lead to pellagra

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Severe deficiencies of vitamin _____ can lead to pellagra

B3

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