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Chemico-Biological Interactions 163 (2006) 94–112

Mitochondrial function and toxicity: Role of the B vitamin
family on mitochondrial energy metabolism
Flore Depeint a,b , W. Robert Bruce b , Nandita Shangari a ,
Rhea Mehta a , Peter J. O’Brien a,∗

Department of Pharmaceutical Sciences, University of Toronto, Canada
b Department of Nutritional Sciences, University of Toronto, CanadaAvailable online 1 May 2006

The B vitamins are water-soluble vitamins required as coenzymes for enzymes essential for cell function. This review focuses
on their essential role in maintaining mitochondrial function and on how mitochondria are compromised by a deficiency of any B
vitamin. Thiamin (B1) is essential for the oxidative decarboxylation of the multienzyme branched-chainketoacid dehydrogenase
complexes of the citric acid cycle. Riboflavin (B2) is required for the flavoenzymes of the respiratory chain, while NADH is
synthesized from niacin (B3) and is required to supply protons for oxidative phosphorylation. Pantothenic acid (B5) is required
for coenzyme A formation and is also essential for -ketoglutarate and pyruvate dehydrogenase complexes as well as fatty acidoxidation. Biotin (B7) is the coenzyme of decarboxylases required for gluconeogenesis and fatty acid oxidation. Pyridoxal (B6),
folate and cobalamin (B12) properties are reviewed elsewhere in this issue. The experimental animal and clinical evidence that
vitamin B therapy alleviates B deficiency symptoms and prevents mitochondrial toxicity is also reviewed. The effectiveness of B
vitamins asantioxidants preventing oxidative stress toxicity is also reviewed.
© 2006 Published by Elsevier Ireland Ltd.
Keywords: B vitamins; Mitochondria; Oxidative stress; Vitamin B therapy

1. Introduction
The aim of this review is to better understand the
relationship between clinical outcome and underlying
mitochondrial disturbances due to B vitamin deficiency.
The B vitamins are water-solublevitamins required as
cofactors for enzymes essential in cell function and
energy production. For each vitamin, we review the
biochemical evidence of absorption, metabolism and
the role of the active form of B vitamins on cellular

Corresponding author at: Leslie Dan faculty of Pharmacy, 19 Russell Street, Toronto, Ont. M5S 2S2, Canada.
Tel.: +1 416 978 2716; fax: +1 416 978 8511.
E-mailaddress: peter.obrien@utoronto.ca (P.J. O’Brien).
0009-2797/$ – see front matter © 2006 Published by Elsevier Ireland Ltd.

function, focusing on reactions relevant to mitochondrial activity and energy metabolism. In this review
the term mitochondrial damage refers to disorders of
mitochondrial integrity and to reactions leading to or
involved in energyproduction. The term mitochondrial
toxins refers to molecules, exogenous or endogenous,
that are known to affect mitochondria or those reactions. Thiamin (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5) and biotin (B7) are reported here,
while pyridoxal (B6), folate and cobalamin (B12) are
reported elsewhere in this issue [1]. We report on current and possible biomarkers for detection of eachof the deficiencies and on evidence of the therapeutic potential of vitamin supplementation. The structures of the vitamins are shown in Table 1. Table 2

F. Depeint et al. / Chemico-Biological Interactions 163 (2006) 94–112
Table 1
Chemical structures of B vitamins



Chemical structure



polished rice. Since then several additional conditions
resultingfrom thiamin deficiency have been observed
in normal populations and in populations affected by
genetic mutations (Tables 2 and 3). Most recently, we
suggested a link between thiamin deficiency and colon
carcinogenesis [4].
2.1. Thiamin delivery from the diet to the






Pantothenic acid



summarizes the clinical conditions...
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