PubMed · 14926099
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A PAZZINI, A BAFFONI. [Sciatica].. https://pubmed.ncbi.nlm.nih.gov/14926099/
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Between the 1950s and 1980s, scientists were focusing mostly on how the genetic code is transcribed to RNA and translated to proteins, but how proteins are degraded has remained a neglected research area. With the discovery of the lysosome by Christian de Duve it was assumed that cellular proteins are degraded within this organelle. Yet, several independent lines of experimental evidence strongly suggested that intracellular proteolysis is largely non-lysosomal, but the mechanisms involved remained obscure. The discovery of the ubiquitin-proteasome system resolved the enigma. We now recognize that degradation of intracellular proteins is involved in regulation of a broad array of cellular processes, such as the cell cycle and division, regulation of transcription factors, and assurance of the cellular quality control. Not surprisingly, aberrations in the system have been implicated in the pathogenesis of human disease, such as malignancies and neurodegenerative disorders, which led subsequently to an increasing effort to develop mechanism-based drugs.
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Advances in Vitamin D nutritional physiology since publication of the DRIs in 1997 are briefly summarized. Available data indicate that (1) Vitamin D's canonical function, optimizing intestinal calcium absorption, is fully expressed at serum 25-hydroxyvitamin D (25OHD) concentration of approximately 80nmol/L; (2) elevated parathyroid activity, typical of aging populations, is minimized at the same 25OHD value and (3) osteoporotic fractures are reduced when serum 25OHD is raised to near 80nmol/L. Depending upon starting value, achieving 25OHD concentrations of 80 or higher may require a daily oral intake of 2200IU (55microg) or more in addition to prevailing cutaneous inputs. The tolerable upper intake level (TUIL), currently set at 2000IU (50microg)/day, is too low to permit optimization of Vitamin D status in the general population. Actual toxicity is not seen below serum 25OHD values of 250nmol/L, a value that would be produced only at continuing oral intakes in excess of 10,000IU (250microg)/day.