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7 Cards in this Set
- Front
- Back
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isoniazid mechanism of action
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inhibits mycolic acid component of mycobacteria cell wall
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why does isoniazid require B6 supplements? (2)
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iosniazid is a competitive inhibitor of pyridoxal kinase (which makes PLP)- shares similar structure. increasing b6 concentrations can drive the reaction in favor of PLP.
isoniazid also binds to pyridoxal B6 and inactivates it |
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specifically what neurotransmitter pathway is affected by lack of pyridoxal B6
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Glutamate (excitatory) --> glutamate decarboxylase (requires PLP)-->GABA
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why does isoniazid cause liver damage in some patients?
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because of difference in speed of metabolism of isoniazid: normally, isoniazid is acetylated and forms an intermediate called acetyl hydrazine (toxic) which is quickly acetylated again to become diacetyl hydrazine, which is easily excreted and not that toxic. Some patients have slow metabolism from acetyl hydrazine to diacetyl hydrazine, so the toxic form accumulates.
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acetyl hydrazine
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toxic metabolite of izoniazid. if accumulated, can be oxidized to form products that react with proteins (can inactivate, or cause immune response) or DNA (trigger apoptosis).
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how to run enzyme assay for AST
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incubate sample of serum with Aspartate (substrate) and a-ketoglutarate. enzyme should be the limiting factor, so add a lot of substrate (but not too high or you will denature the enzyme). amount of substrate needs to be higher than double the Km concentration, to compensate for substrate consumption
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AST rxn
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aspartate--> transfer amino group from aspartate to a-ketoglutarate (becomes glutamate)-->deaminated aspartate = oxaloacetate (ketoacid)
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