High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased K(m)): relevance to genetic disease and polymorphisms.
Level 5 - mechanism / opinion, no new human data
Narrative review describing biochemical mechanisms and theoretical applications without new empirical data
PubMed 11916749 · doi:10.1093/ajcn/75.4.616
What was done
This narrative review examined the biochemical mechanism by which gene mutations reduce coenzyme binding affinity (increase the Michaelis constant, Km) in variant human enzymes, and summarized evidence for using high-dose vitamin therapy to restore enzymatic activity in genetic diseases and single-nucleotide polymorphisms.
What was found
The authors report that up to one-third of mutations in a gene increase the Km for a coenzyme, lowering the reaction rate. About 50 human genetic diseases caused by defective enzymes are reported to be remedied or ameliorated by high doses of the corresponding vitamin cofactor. Several common polymorphisms with reduced coenzyme binding are highlighted as potentially remediable via high-dose vitamin therapy, including MTHFR 677C->T (Ala222Val with FAD cofactor), NQO1 609C->T (Pro187Ser with FAD), G6PD 131C->G (Ala44Gly with NADP), and ALDH2 Glu487Lys (with NAD, present in roughly half of Asian populations).
Why it matters
This paper provides a unifying biochemical framework explaining how supraphysiological vitamin supplementation can overcome reduced cofactor binding affinity across a wide range of inborn errors of metabolism and common genetic variants.
Limits
The abstract describes a narrative conceptual review rather than a systematic review, clinical trial, or meta-analysis. It does not provide quantitative clinical outcome data, trial sample sizes, or toxicity profiles for high-dose vitamin regimens.
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