A 49-year-old man comes to the office due to "aching bones." He has a 2-month history of insidious-onset pain that is most pronounced in the back, pelvis, and lower extremities. The pain is dull and increases after weight-bearing activities. The patient has no prior medical conditions and takes no medications. He emigrated from Central Africa 5 years ago and works overnight shifts as a cab driver. Vital signs are within normal limits. Physical examination shows normal muscle strength in the upper and lower extremities bilaterally. A thorough laboratory evaluation establishes the diagnosis. After discussing the likely cause of his condition, the patient starts spending more time outdoors in the sun. Which of the following enzymatic steps will most likely be affected by this change in activity?

Question

A 49-year-old man comes to the office due to "aching bones."  He has a 2-month history of insidious-onset pain that is most pronounced in the back, pelvis, and lower extremities.  The pain is dull and increases after weight-bearing activities.  The patient has no prior medical conditions and takes no medications.  He emigrated from Central Africa 5 years ago and works overnight shifts as a cab driver.  Vital signs are within normal limits.  Physical examination shows normal muscle strength in the upper and lower extremities bilaterally.  A thorough laboratory evaluation establishes the diagnosis.  After discussing the likely cause of his condition, the patient starts spending more time outdoors in the sun.  Which of the following enzymatic steps will most likely be affected by this change in activity?

Quizplus · Accepted Answer

11ec160b_3d05_6e4a_9249_99bb54021e85_MD0001_00 On exposure to sunlight, 7-dehydrocholesterol (provitamin D3) in the skin absorbs ultraviolet (UV) B rays. This opens the B ring of 7-dehydrocholesterol, forming previtamin D3, which then undergoes thermal isomerization to form vitamin D3 (cholecalciferol). Vitamin D3 is then hydroxylated in the liver to 25-hydroxyvitamin D and subsequently to 1,25-hydroxyvitamin D (the active form) in the kidneys. Vitamin D deficiency can lead to osteomalacia with bone pain or tenderness, muscle weakness or cramps, gait abnormalities, and increased fracture risk. Factors associated with limited UV exposure and increased risk of vitamin D deficiency include the following: (Choices B and C) The conversion of vitamin D2 and D3 to 25-hydroxycholecalciferol by 25-hydroxylase in the liver is primarily regulated by feedback inhibition from 25-hydroxycholecalciferol. The conversion to 1,25-dihydroxycholecalciferol by 1-alpha-hydroxylase in the kidney is primarily regulated by parathyroid hormone (PTH) and plasma calcium levels. Neither of these steps takes place in the skin or is affected by sunlight exposure. (Choices D and E) 25-hydroxyvitamin D-24-hydroxylase converts 25- and 1,25-dihydroxyvitamin D into inactive 24-hydroxylated metabolites. It is upregulated by 1,25-dihydroxyvitamin D (to prevent excess vitamin D activity) and suppressed by parathyroid hormone (to facilitate replenishment of circulating calcium levels) and thus functions as a counter-regulatory homeostatic enzyme. However, it is not affected by sunlight. Educational objective: Sunlight exposure catalyzes conversion of 7-dehydrocholesterol to cholecalciferol (vitamin D3) in the skin. Subsequent 25-hydroxylation in the liver and 1-hydroxylation in the kidneys produce 1,25-dihydroxyvitamin D, the active form. Inadequate exposure to sunlight can lead to vitamin D deficiency. __________ References: Sunlight, ultraviolet radiation, vitamin D and skin cancer: how much sunlight do we need? (http://www.ncbi.nlm.nih.gov/pubmed/25207357)

A 49-Year-Old Man Comes to the Office Due to "Aching