Heme, iron, and the mitochondrial decay of ageing
Heme, the major functional form of iron, is synthesized in the mitochondria. Although dis-
turbed heme metabolism causes mitochondrial decay, oxidative stress, and iron accumulation, all
of which are hallmarks of ageing, heme has been little studied in nutritional deficiency, in ageing,
or age-related disorders such as Alzheimer’s disease (AD). Biosynthesis of heme requires Vitamin
B6, riboflavin, biotin, pantothenic acid, and lipoic acid and the minerals zinc, iron, and copper,
micronutrients are essential for the production of succinyl-CoA, the precursor for porphyrins, by
the TCA (Krebs) cycle. Only a small fraction of the porphyrins synthesized from succinyl-CoA are
converted to heme, the rest are excreted out of the body together with the degradation products of
heme (e.g. bilirubin). Therefore, the heme biosynthetic pathway causes a net loss of succinyl-CoA
from the TCA cycle. The mitochondrial pool of succinyl-CoA may limit heme biosynthesis in defi-
ciencies for micronutrients (e.g. iron or biotin deficiency). Ageing and AD are also associated with
hypometabolism, increase in heme oxygenase-1, loss of complex IV, and iron accumulation. Heme
is a common denominator for all these changes, suggesting that heme metabolism maybe altered
in age-related disorders. Heme can also be a prooxidant: it converts less reactive oxidants to highly
reactive free radicals. Free heme has high affinity for different cell structures (protein, membranes,
and DNA), triggering site-directed oxidative damage. This review discusses heme metabolism as
related to metabolic changes seen in ageing and age-related disorders and highlights the possible
role in iron deficiency.
