Welcome to the next lecture in Leaning Unit 3 where you will learn about the importance of nutrients in animal life I am Dr Peter Ferket and this lecture is about the skeletal system and the importance of calcium phosphorus and vitamin D In learning unit 2 you learned some basic concepts of calcium and phosphorus in the lecture about minerals and about vitamin D in the lecture about vitamins In this lecture we will discuss how these nutrients function in the formation and maintenance of the skeletal system in animals using the human as the primary reference model 1 Calcium and Phosphorus nutrition is critical for skeletal development and maintenance The requirements and metabolism of calcium phosphorus and vitamin D are closely interrelated Mineralized bone consists mainly of tricalcium phosphate and other salts that include magnesium boron sodium and silica Primarily hydroxyapatite Ca10 PO4 6 OH 2 which is laid down on collagen matrix during bone formation About 99 of the calcium and 80 of the phosphorus in the animal body occur in the bones and teeth Phosphorus has a multitude of functions It is a structural component of bones and teeth as an anion in hydroxyapatite It s a component of DNA and RNA high energy compounds such as ATP and creatine phosphate and a component of phospholipids in cellular 3 membranes Phosphorus controls the activation of certain enzymes through phosphorylation or dephosphorylation and phosphoproteins such as calmodulin and glutaminase Finally phosphorus is critical for acid base balance 3 Calcium also serves several non structural roles such as An Enzyme cofactor lipases hydrolases Blood clotting cascade Relaxation and constriction of blood vessels Cell aggregation and adhesion Muscle protein contraction Cellular protein turnover Hormone secretion Nervous impulse transmission Cell signaling 4 What is interesting about Vitamin D is that it is the only vitamin that is not required in the diet provided there is enough exposure to sunlight This sunshine vitamin is actually a hormone produced from steroids in the body by the photolytic action of ultraviolet light on the skin of individuals who receive modest exposures to sunlight However animals raised in environmentally controlled confinement and people who spend all or most of their days indoors especially in Northern latitudes need a dietary source of Vitamin D 5 The risk of vitamin D deficiency is distributed throughout the world is inversely related to the intensity of ultraviolet light exposure from the sun Populations living at global latitudes of about 40 degrees North or South do not get sufficient exposure to sunlight for at least one month of the year but because most people spend their time indoors or they cover themselves with sunscreen when they do go out in the sun most people do not get sufficient sunlight exposure 6 The major physiological role of vitamin D is to regulate the absorption of calcium from the intestine by regulating the mucosal synthesis of calcium binding protein calbindin However Vitamin D has many other functions as a regulatory hormone There are some interesting differences among species in vitamin D regulation of calcium absorption reflecting evolutionary background For example llamas have a high dietary vitamin D requirement because in their native habitat at high elevations in the Andes they are exposed to intense solar radiation Vitamin D has several biological functions all related in some part to calcium metabolism These function include bone health muscle function immune function mental health heart health diabetes and cancer and how vitamin D acts on each of these function is listed for your review 8 There are several forms vitamers of vitamin D that are known collectively as calciferol The two major forms are vitamin D2 or erocalciferol and vitamin D3 or cholecalciferol Ergocalciferol Vitamin D2 has a double bonds in the non cyclic carbon chain originating from ergosterol in plants fungi molds lichens and some invertebrates e g snails and worms In fact Ergosterol was named for the parasitic fungus of oats ergot from which the sterol was first isolated Cholecalciferol Vitamin D3 is widely distributed in animals in which its provitamin D form 7 dehydrocholesterol is a normal metabolite Cholecalciferol is not found in plants but most animals can convert Erogocalciferol to Cholecalciferol It is noteworthy that dietary requirement of Cholecalciferol is higher for poultry than mammals due its greater affinity to binding proteins Vitamin D is a generic term and indicates a molecule of the general structure shown for rings A B C and D with differing side chain structures The A B C D ring structure is derived from the ring structure for steroid Technically Vitamin D is classified as a seco steroid Seco steriods are those in which one of the rings has been broken in Vitamin D the 9 10 carbon carbon bond of the ring B is broken 9 Vitamin D metabolites arise from two potential sources photo dependent biosynthesis or by dietary sources As mentioned previously in this lecture Vitamin D can be biosynthesized in the skin from 7 dehydrocholesterol which originates from aceytl CoA synthesis to cholesterol 7 dehydrocholesterol can also be absorbed from the diet and then converted to cholcalciferol Vitamin D3 in the skin Cholcalciferol can also be absorbed in the diet Vitamin D3 entering the circulation system form the skin or intestine then goes to the liver where it is converted to 25 hydroxy D3 calcidiol by hydroxylation of the side chain carbon C 25 with the enzyme Vitamin D 25 hydroxylase This reaction occurs in the liver in mammals but occurs in both the kidney and liver in birds In the kidney the initial hydroxylation product of 25 OH D3 is further hydroxylated at the C 1 position of the A ring to yield 1 25 OH 2 D3 catalyzed by 25 OH vitamin D 1 hydroxylase This activity is primarily in renal cortical mitochondria but also in mitochondrial and microsmal fractions of at lease some extrarenal tissues such as bone cells liver and placenta 25 OH vitamin 1 hydroxylase is activated when blood calcium and phosphorus is low The hydroxylation of the C 24 of the side chain can occur to 25 OH D3 to produce 24 25 OH 2 D3 10 In all animals calcium absorption is regulated by need via the calcitriol 1 25 OHD3 pathway and ultimately controlled by the serum calcium concentration Serum calcium is homeostatically regulated by the actions of parathyroid hormone PTH in response to hypocalcaemia