11:22:11 - Review for Exam III (Part 2)

11:22:11 - Review for Exam III (Part 2) - Iron - Fe 2 – 4...

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Unformatted text preview: Iron - Fe 2 – 4 g of iron present in the human body 39 mg/kg female 50 mg/kg male Distribution >65% hemoglobin - Iron-containing oxygen-transport metalloprotein in the red blood cells. 10% myoglobin an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in almost all mammals 1-5% part of enzymes Remainder found in blood or storage Amount is dependent on body weight, gender, age, pregnancy, growth state. Types: Heme iron – or “animal source” is found in the hemoglobin and myoglobin of animal products in the diet. (50 – 60% of animal tissue protein) Nonheme iron – or “plant source” bound to components of food. (plant and some animal source, milk) Digestion and Absorption • Heme iron: hydrolyzed by proteases in stomach and small intestine. It must be released from the porphyrin ring •Heme carrier protein is present in the proximal small intestine. •Heme iron absorption takes place throughout the small intestine but is most efficient in the proximal duodenum. • Iron can bind with ligands and chelating agents. If the bonds are strong and insoluble iron will not be absorbed. Structure Digestion and Absorption • Heme iron: hydrolyzed by proteases in stomach and small intestine. It must be released from the porphyrin ring • Heme carrier protein is present in the proximal small intestine. • Heme iron absorption takes place throughout the small intestine but is most efficient in the proximal duodenum. • Iron can bind with ligands and chelating agents. If the bonds are strong and insoluble iron will not be absorbed. Fig. 12-2, p. 472 Absorption enhanced by: acids - ascorbic, citric, lactic and tartaric acid sugars (esp. fructose and sorbitol) meat, poultry and fish – cysteine and histidine mucin – acts as s chelate that aids iron absorption These chemicals can act as chelating agents or ligands that bind with iron and enhance absorption Vitamin C - is especially helpful for iron absorption. Absorption inhibited by: polyphenols – coffee and tea oxalic acid – in chard berried, chocolate and tea phytates – in whole grains and cereals phosvitin – a protein found in egg yolks nutrients such as calcium, calcium phosphate salts, zinc, manganese, and nickel These chemical bind iron in the intestinal lumen and decrease iron absorption Regulation Hepcidin – protein secreted by the liver in response to adequate iron levels. causes ↓’d levels of ferroportin – stops iron absorption. HFE – promotes uptake of iron by transferrin Dcytb and DMT1 – promote iron absorption The body will store some iron in the intestinal cells as apoferritin. The intestinal cells will also use iron for a variety of purposes such as cofactor for enzymes. Transport Transfer across the basolateral membrane requires ferroportin. Iron is reduced to Fe2+ for absorption then is oxidized to Fe3+ for transport Hephaestin and ceruloplasmin are two copper containing proteins that oxidize iron. is transported by transferrin in the blood stream. Iron Transferrin typically is 33% saturated with iron. Storage Fe is stored in the cell as ferritin. 1) Liver – stores about 60% of body’s iron 2) Bone marrow 3) spleen Ferritin is not stable – constantly being degraded and resynthesized. So creates a cellula pool. ↓ cellular iron ↓ ferritin synthesized ↑ cellular iron ↑ ferritin synthesized Equilibrium between tissue ferritin and serum ferritin. So serum ferritin can help indicate body stores. Function Hemoglobin and myoglobin – hemoglobin is synthesized in the RBC Cytochromes – heme-containing cytochromes b and c in the electron transport chain Iron is alternately reduced and oxidized as electrons are transferred. Monooxygenases and dioxygenases – Many of these enzymes requires iron for their action of inserting oxygen into a substrate. Peroxidases , oxidoreductases, and other proteins. Interactions with other nutrients: Vitamin C – absorption and release from ferritin. Copper – hephaestin and ceruloplasmin to oxidize iron. Zinc – excessive amounts of nonheme iron in a meal have been shown to inhibit zinc absorption. Vitamin A - ↓ amounts of vitamin cause accumulation of iron in organs such as the spleen and liver. Also see altered RBC morphology as well as ↓’d hemoglobin and hematocrit. caused by ↓’d synthesis of erythropoietin. Lead – related to iron deficiency – inhibits heme synthesis and addition of iron to hemoglobin. Selenium – iron deficiency associated with decreased selenium concentration. Turnover Daily intake cannot meet body needs – therefore body conserves iron. Most iron is stored as ferritin and hemosiderin. Body will reuse the iron from hemoglobin, ferritin and hemosiderin. Excretion Sites of iron loss: 1) gastrointestinal tract 2) skin 3) kidney Daily iron loss: Male: 0.9 – 1.0 mg/day Female : 0.7 – 0.9 mg/day* * Postmenopausal Premenopausal women avg: 1.3 – 1.4 mg/day Can lose 17.5 mg/period Deficiency Most often due to inadequate intake. Populations groups at risk: 1)Infants and young children: low content of milk and other preferred foods, rapid growth and insufficient stores. 2) Adolescents: rapid growth and expanding RBC mass. 3)Pregnant women: expanding blood volume, needs of fetus and placenta, and blood loss due to childbirth. 4) Females during childbearing years: regular menstrual iron losses. Other clinical situations: Hemorrhage, renal disease, renal placement therapy, decreased GI transit time, Steatorrhea, parasites. Deficiency without anemia: Can be seen in children – symptoms: pallor, listlessness, behavioral disturbances, impaired performance on some cognitive tasks, some irreversible impairment in learning ability, short attention span. Adults – symptoms: impaired work performance and productivity, impaired immune system, decreased resistance to infection, impaired ability to maintain body temperature. Fig. 12-8, p. 486 Assessment Common: Hemoglobin – measure of iron containing protein found in RBC. Hematocrit – the proportion of total blood volume that are RBC. Problem: these measures are the last to change in iron deficiency. Often use measure of plasma ferritin levels to assess stores. Problem: these can be elevated if there is inflammation. As iron deficiency progresses, see a decrease in transferrin saturation. normal: 33% deficiency: <16% When deficiency has finally affected HgB (<12 g/dL female and <13 g/dL male) and hematocrit (<37% female and <40% male) see: ↓ MCV – mean corpuscular volume (size of RBC) ↓ MCH – mean corpuscular hemoglobin (average hemoglobin content of each RBC) ↓ MCHC – mean corpuscular hemoglobin concentration (amt of hemoglobin in g/dL of RBC. See hypochromic (pale) microcytic (small) anemia. Toxicity emochromatosis – genetic disorder, seen in 50/10,000 in US. ost often seen in Caucasian males. 2 x’s normal iron absorption. aused by mutation in HFE gene. Intestinal cells are unable to accurately sense iron stores and down regulate intestinal absorption. on is deposited in joints, liver, heart and pancreas – causes organ damage and eventually organ failure. reatment: 1) removal of 400-500 ml of blood per week. 2) Deferoxamine – chelating agent that binds to iron in the blood and increase urinary excretion. Zinc Zinc Is found in all organs and tissues although primarily intracellularly. • Heating can cause zinc to form complexes that resist hydrolysis. Example: Maillard reaction: amino acid-carbohydrate complex formed in browning. • GI tract will hydrolyze enzymes after use and absorb zinc rather than lose through • proteases, nucleases and HCl feces. •Meds that increase pH of stomach (antacids, beta blockers) will tend to inhibit zinc release from foods. Absorption 10 – 59% absorbed. 1)Carrier mediated – improves with larger intake 2)Passive diffusion Absorption is most efficient in the jejunum but can occur throughout the small intestine. Factors enhancing absorption Several substance can act as ligands that aid absorptions: citric acid, prostaglandins, amino acids: histidine, cysteine, pancreatic secretions, products of protein digestion. Factors inhibiting zinc absorption Phytate, oxalic acid, polyphenols, minerals: nonheme iron, calcium and copper. nce in the enterocyte zinc can be: 1) used functionally by the cell 2) stored 3) transported through the cell and across the basolateral membrane into the plasma. Transport There are several zinc transporters to move zinc in and out of various cells. Zinc is bound to albumin for transport through the blood to the liver. When leaving the liver, zinc can be bound to albumin (60%) transferrin immunoglobulin α-2 macroglobulin. Distribution and Storage Zinc is found in all body organs. Not part of the zinc pool – protected. If dietary zinc is low, body will degrade “less essential” enzymes. Theory: zinc is stored in tissues as part of metallothionein. 15 – 40% Functions Primary function as cofactor for enzymes Zinc-dependent enzymes: used by enzymes both for function and structural integrity Cell replication Zinc interacts with transcription factors. Acts as a structural component as “zinc fingers”. Will bind to retinoic acid (vitamin A) and 1,25 – (OH) 2 vitamin D Cell membranes – structure and support when they interact with transcription factors in the nucleus. Carbohydrate metabolism Zinc deficiency will decrease insulin response which will impair glucose tolerance. Host defense and immunity Interactions with other nutrients Vitamin A – alcohol dehydrogenase: retinol → retinal hepatic synthesis of retinol-binding protein (transport Vitamin A) Copper - ↑ zinc → production of thionein (metallothionein when zinc is bound to it) this will trap copper and prevent transport out of the enterocyte. Calcium – if calcium intake is low (<300mg) presence of zinc can decrease calcium absorption. Cadmium – can replace zinc on common enzyme bonding sites. Deficiency Symptoms: growth retardation (young children); skeletal abnormalities from impaired development: epiphyseal cartilage, defective collagen synthesis; poor wound healing; dermatitis; delayed sexual maturation (young children); roups as risk: elderly hypogeusia; alopecia; impaired immune function; impaired protein synthesis. vegans alcoholics patients with chronic illnesses, stress, trauma, surgery, malabsorption Toxicity Tolerable upper level: 40 mg/day – regular ingestion of this amount will result in Cu deficiency 1-2g zinc sulfate can result in: metallic taste, nausea, vomiting, epigastric pain, abdominal cramps, bloody diarrhea. Excretion 1)GI tract – lost proteins in feces and sloughed intestinal cells 2)Kidneys – small amount in urine, most reabsorbed 3)Skin – exfoliation and sweat Copper Dietary sources of copper are influenced by: origin, production, handling, and processing. Digestion and Absorption HCl and pepsin release Copper from food components, frequently amino acids. Primary absorption through duodenum but can also be absorbed from the stomach. Absorption is both carrier mediated and passive diffusion. Copper is reduced for all phases of absorption. Typically 50% of dietary copper is absorbed. Varies with dietary levels. low dietary copper - >50% high dietary copper - <20% Factors enhancing Copper absorption Amino acids: histidine, methionine and cysteine Acids form binding ligands: acetic, lactic, gluconic, citric and malic acids. Factors that inhibit Copper absorption Phytate Zinc Iron Molybdenum Calcium Phosphorus Vitamin C Excessive antacids Copper can be stored as metallothionein (like zinc) in the enterocyte or move on to Be absorbed across the basolateral membrane. Transport Methods of transport: 1)Albumin – primary method 2)Transcuprein 3)Histidine/cysteine Storage • Liver thought to regulate copper levels in the body. • Copper is found in a variety of tissue/organs but primarily in liver, kidney and brain. Functions 1) Primary function: an enzyme cofactor. 2) Angiogenesis 3) Immune function 4) Nerve myelination 5) Endorphin action Interaction with other nutrients Vitamin C – inhibits absorption Zinc – strong mutual antagonism Iron – related to iron metabolism (oxidizes iron as it leaves the cells). Copper deficiency can promote anemia. Molybdenum – forms an insoluble complex Deficiency Symptoms: hypochromic anemia, leukopenia, hypopigmentation of skin and hair, impaired immune system, bone abnormalities, cardio vascular and pulmonary dysfunction. Associated with: excess intake of zinc or antacids or increased loss of copper as seen in GI malabsorptive disorders (celiac disease, tropical sprue, and inflammatory bowel disease. Toxicity Tolerable upper level: 10 mg/day Symptoms: epigastric pain, nausea, vomiting, diarrhea, hematuria, liver and kidney damage (oliguria or anuria). Wilson’s disease – genetic disorder . See accumulation of copper in tissue. Treatment: low copper diet, zinc and molybdenum supplements to bind dietary copper and D-penicilllamine therapy to bind body copper and increase excretion. Excretion Primary excretion through bile. Biliary copper loss in the feces regulates copper balanc If copper intake is low, biliary copper loss through feces falls. Small amounts are lost through urine and sweat. Selenium Chemistry is similar to sulfur. Can substitute for sulfur. Absorption Organic form (found in food): selenomethionine, selenocysteine Inorganic forms (some vegetables, yeast, and supplements): selenite, selenate, selenide Duodenum is primary site but can also be absorbed from jejunum and ileum. The organic forms, selenomethionine and selenocysteine are absorbed via the amino acid transport systems. elenium is transported as selenoamino acids of VLDLs, LDLs and other blood proteins. Storage Selenium is found in many organs and tissues. Highest: thyroid gland, kidney, liver, heart, pancreas, and muscle. Functions Primary function: as part of selenium-dependent enzymes. Other functions exist but are poorly understood. Common selenium –dependent enzymes: Glutathione Peroxidase (GPX 1-4) – catalyzes removal of hydrogen peroxides and hydroperoxides. Iodothyronine 5’-Deiodinase (IDI or DI) – catalyze the removal of iodine from thyroxine. Interactions with other nutrients Iron – iron deficiency ↓’s synthesis of hepatic GPX and ↓’s tissue Se concentrations Copper – Copper deficiency ↓’s activity of both GPX and IDI Methionine – if selenium is only available as selenomethionine, limits selenium availability (only available when protein is degraded). Deficiency nked to: 1) Keshan disease – cardiomyopathy involving cardiogeneic shock or CHF or both Coxsackie virus is a cofactor – insufficient selenium causes normally benign virus to become virulent. Believed to account for some of the symptoms. 2) Kashin-Beck’s disease – osteoarthropathy ( degeneration of joints and epiphyseal cartilage of legs and arms). 3) Patients receiving TPN – symptoms: poor growth, muscle pain and weakness, loss of pigmentation in skin and hair, and whitening of nail beds. Toxicity - selenosis Tolerable upper level: 400 μg/day Seen in miners as well as people that ingest high levels of supplements. Symptoms (seen with 910 μg dose): nausea, vomiting, fatigue, diarrhea, hair and nail brittleness and loss, paresthesia, interference with sulfur metabolism. Excretion rimary excretion routes: urine and feces (believed to be regulation method) ome loss through lungs and skin. Iodine Levels in foods are affected by soil content. Amount in water is affected by levels in Rocks and soil. Examples: India – Nepal and Ceylon : 0.1 – 1.2 mg/L New Delhi: 9.0 mg/L USA – Great Lakes area – very low, saw high incidence of goiter before iodized salt. Digestion and Absorption Dietary iodine tends to be found bound to amino acids or free. After release, various forms as well as T4 nd T3 can be easily Iodine is transportedafreely in the blood. absorbed. Digestion and Absorption Dietary iodine tends to be found bound to amino acids or free. After release, various forms as well as T4 and T3 can be easily absorbed. Iodine is transported freely in the blood. Storage Thyroid gland aggressively traps iodine – other organs: ovaries, placenta, skin salivary, gastric and mammary glands. Function Primary function: as part of thyroxine (T4) and triiodothyronine (T3). Three carriers: Thyroxine-binding globulin, albumin, and transthyretin. T4 needs to be diiodinated to the active form by IDI (selenium) Key tissues that can do this: liver, pituitary, brain, brown adipose tissue. Thyroid hormones: stimulate basal rate of metabolism stimulate oxygen consumption stimulate heat production necessary for normal nervous system development necessary for normal linear growth Interactions with other nutrients Goitrigens – affect uptake of iodine by thyroid and cause augment TSH release so thyroid gland becomes enlarged. They compete with iodine for active transport into the thyroid gland Some goitrogens: bromide, astatide, thiocyanate, perrhenate, pertechnetate, lithium Cruciferous vegetables contain goitrins – would need to be consumed in VERY large quantities Cassava – contains linamarin – converts to thiocyanate Deficiency Release of thyroid hormones is regulate between the hypothalamus an d pituitary gland Hypothalamus responds to ↓’d levels of T4 . Sends signal to pituitary gland to release TSH. Dietary iodine deficiency causes ↓’d levels of T4 and over release of TSH. Result is simple goiter. Goiter is enlarged thyroid gland. As it enlarges, it is able to trap more iodine. SO the enlargement is self limiting. Can return to normal size over time with addition of iodine to the diet. When over 10% of a population has goiter it is labeled endemic goiter. Iodine (iodide) deficiency in infants can result in cretenism. Neurological Cretinism: mental deficiency, hearing loss or deaf mutism, spaticity and muscle rigidity Hypothyroid cretinism: thyroid failure. Toxicity Tolerable upper level: 1,100 μg/day. Adverse effects seen at 1,700 μg/day. Symptoms: burning of the mouth, throat and stomach, nausea, vomiting, diarrhea and fever. Can affect function of thyroid gland. Excretion Primary route of excretion: urine Kidney does not reabsorb so: daily urine output of iodide is considered to accurately reflect dietary intake. ...
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