Background: Dietary protein promotes growth and regulates appetite. In the gut, protein elicits digestive, absorptive and hormonal responses that facilitate nutrient disposal and the control of growth. In bone, dietary protein promotes bone density and resistance to fracture. The molecular and cellular mechanisms that underlie these effects of protein, however, have been poorly understood.
Review: As dietary protein intake changes, serum and intracellular amino acid levels also change and recent research indicates that the body is equipped with sophisticated amino acid sensing mechanisms for detecting and responding to states of feast - and famine. The molecular mechanisms that are emerging are predominantly intracellular in the case of amino acid famine and predominantly extracellular in the case of amino acid plenty. Mechanisms for amino acid depletion are based on the generation of amino acid-free forms of transfer RNA and operate, for example, to regulate appetite, perhaps even the appetites for specific types of foods. Two basic mechanisms appear to operate in the case of amino acid plenty. One is based on amino acid transporters and the other on class 3 G-protein coupled receptors, some of which bind multiple amino acids in their extracellular bilobed “Venus FlyTrap” domains. Expression of these receptors in the gut provides mechanisms by which amino acids contribute to the control of digestion and absorption. Expression in endocrine cells, on the other hand, provides mechanisms by which the synthesis and/or secretion of growth-regulating hormones can be regulated. Finally, amino acid modulation of calcium-sensing receptors provides a mechanism by which protein and calcium metabolism are linked providing insights into the molecular control of bone homeostasis.
Conclusions: The cellular and molecular mechanisms responsible for detecting and responding to changes in dietary protein intake are, at last, coming to light.
Reference
AD Conigrave and DR Hampson (2006) Broad-spectrum amino acid sensing by class 3 G-protein coupled receptors. Trends Endocrinology and Metabolism, in press.