Haem in the gut. I. Fate of haemoproteins and the absorption of haem

Haem (FeII-protoporphyrin-IX) is presented to the gut lumen as haemoproteins derived from exogenous dietary) and endogenous (mucosal cell desquamation and bleeding) sources. Haemoproteins such as haemoglobin, myoglobin and catalase undergo hydrolysis by luminal proteases to release the haem. Released haem is maintained in a soluble form in the gut lumen by the products of haemoprotein digestion. Chelators of elemental iron do not bind haem-iron and so haem-iron is better absorbed than elemental iron. Haem-iron does not exchange with luminal elemental iron. Mucosal uptake of haem is limited. Less than 10% binds to the brush border of the villus cell. Although the mechanisms by which haem binds to the brush border and is transported to the intracellular environment are poorly understood, it is known that some haem is transferred to secondary lysosomes where the porphyrin ring is split to release iron and form bilirubin. Depending upon the composition of the diet, the iron released from haem within the villus cell can be the major physiological source of iron. In iron-deficiency in humans, absorption of haem-iron can increase threefold whereas absorption of elemental-iron can increase tenfold. These observations indicate that haem-iron and elemental-iron are absorbed via different mechanisms which are subject to different regulation. For haem-iron to be absorbed, the haem itself must be taken up by the mucosa.     

A model systems approach to age-related memory disorders

Memory deficits are common to virtually all forms of cognitive dysfunction and are central to disorders associated with aging. Animal models provide the opportunity to understand normal and pathologic memory in great detail. The model systems approach to the neurobiology of memory involves studying a well characterized learned response in a relatively simple and well controlled preparation. The best characterized mammalian model system is classical conditioning of the rabbit's eyeblink response. Using this preparation, significant progress has been made toward understanding the neurobiological systems and mechanisms involved in elaboration of the conditioned response. Using a well characterized model system such as classical eyeblink conditioning, it should be possible to both characterize the changes in learning and memory that accompany aging and to investigate their neural substrate. Our strategy for using the conditioned eyeblink preparation for studying age-related memory deficits is fourfold and includes investigating conditioning deficits in: (1) humans across the life-span, (2) rabbits across the life-span, (3) Alzheimer's disease patients, and (4) rabbits with aluminum-induced neurofibrillary degeneration. In this paper, we present exemplary data from each of these lines of research. If similar deficits occur in each of these groups, it may be possible to begin to form hypotheses about the neurobiology of age-related memory disorders.