Vitamin B5 (Pantothenic Acid) and Vitamin B6 (Pyridoxine)

Mechanism

Cellular biochemical mechanisms

1. Pantothenic Acid (Vitamin B5) and Coenzyme A

Cellular pantothenic acid is phosphorylated and coupled to cysteine through the energy expenditure of ATP to become Coenzyme A (CoA-SH). The free thiol group (-SH) of CoA acts as a nucleophile transporting acyl radicals with high energy transfer, participating in the synthesis of body lipids, acetylation of neurotransmitters and in the entry of substrates to the Krebs Cycle in the form of Acetyl-CoA.

2. Pyridoxine (Vitamin B6) and Pyridoxal Phosphate (PLP)

Pyridoxine, pyridoxal and pyridoxamine are converted in the cytosol to the active coenzyme Pyridoxal Phosphate (PLP). PLP acts in the nitrogen metabolism of body amino acids:

• Transamination: Reversible reactions catalyzed by aminotransferases (AST/ALT) that transfer the amino group of an amino acid to an α-keto acid for the synthesis of new metabolites. The mechanism involves the cyclic conversion of PLP to pyridoxamine phosphate (PMP): Amino acid + PLP-Enzyme leftharpoons Ketoacid + PMP-Enzyme
• Decarboxylation: Essential for the synthesis of essential neurotransmitters: histidine to histamine, dopa to dopamine, tryptophan to serotonin and glutamic acid to GABA.
• Emergence of Hemoglobin (Porphyrin Synthesis): It acts as a limiting cofactor of the enzyme δ-aminolevulinate synthase (ALA-synthase) in the first mitochondrial stage of synthesis of the Heme group.

Indicators and dose

Clinical Indications and Drug Adjustment

• Treatment of Microcytic Sideroblastic Anemia: The genetic or acquired deficiency of ALA-synthase interrupts the incorporation of iron into the Heme group, accumulating it in the perinuclear mitochondria of the erythroblasts. Responds partially to PLP supplementation.
• Prevention of Neuropathy by Medications (Isoniazid): The anti-tuberculosis drug isoniazid reacts directly chemically with pyridoxal and PLP, forming an inactive hydrazone for rapid renal excretion. Its use without B6 supplementation induces peripheral neuropathy due to tissue depletion. It is mandatory to prescribe 25-50 mg of pyridoxine per day together with isoniazid.

Security

Risk of Sensory Neurotoxicity due to Chronic Overdose

Unlike most water-soluble vitamins that are easily excreted by the kidneys, chronic use of megadoses of pyridoxine (> 500 mg/day) induces symmetrical and irreversible painful sensory neuropathy. The mechanism is associated with the saturation of the cellular enzyme systems of tissue phosphorylation, causing competitive inhibition by non-phosphorylated pyridoxine on the intracellular PLP receptors in the spinal dorsal root ganglion neurons.