Iron Metabolism/Ca And Other Minerals Flashcards
Iron in non-heme structures
. Non-heme proteins have iron-sulfur cluster proteins (NADH dehydrogenase, dehydrogenase, ferrochelatase)
. Single Fe-containing proteins (Phe hydroxylase)
. Oxygen-bridged iron (ribonucleotide reductase)
Amount of Fe in adult
. 2-4 g w/ 60-70% present in Hb
. Remainder in Mb or storage
Iron found in diet
. Heme Fe: less abundant but readily absorbed (red meat, poultry, some fish)
. Non-here Fe: more abundant but not as easily absorbed (enriched cereal, spinach, lentils, and beans)
Enhancers of Fe absorption
. Vit. C
. Organic acids
. Reducing sugars
. Meat factor
Inhibitors of absorption
. Dietary fibers/phytates (grains, veggies) . Polyphenols veggies, tea, coffee) . Ca . Carbonates . Polyphenols . Oxalates . Tannates (tea, coffee)
Fe homeostasis
. Closed system, losses o only 1-2 mg/day and are unregulated
. Maintenance dependent on regulation of absorption
. Hepcidin (25-AA antimicrobial) synthesized in hepatocytes binds to ferroportion to promote cellular internalization of hepcidin-ferroportin complex and lysosomal degradation
Potential causes of Fe deficiency
. Inadequate absorption: poor bioavailability, antacid therapy, excess dietary bran or starch, competition from other metals, low/dysfunctional enterocytes, bowel resection, celiac, IBD)
. Inc. loss: GI, GU, Pulmonary, or other blood losses
Anemia of chronic disease
. Occurs as consequence of cytokines-mediated impaired ability to boiling Fe from storage stores and neg. effects on EPO production and erythropoesis
. Treat underlying disease
. Blood transfusions
. Administration of erythropoietic agents
Hereditary hemochromatosis
. Genetic disorder of Fe metabolism where Fe absorption is unregulated and excess Fe is deposited in organs (liver, pancreas, heart, joints, skin)
. Leads to liver cirrhosis, hepatocellular carcinoma, DM, HF, and arthritis
. Type one is assoc. w/ HFE gene mutation
. Treatment: regular phlebotomy
Secondary forms of Fe overload
. Consequence of chronic transfusion therapy in patients w/ thalassemia and aplastic anemia
Calcium
. Most abundant mineral in body (1,000 g)
. Important in m. Contraction, hemostasis, and cell signaling
. Highly regulated w/in 9-10 mg/dL
. Achieved via PTH, vit. D, and calcitonin on bone, kidney and intestine
Ca homeostasis
. Plasma Ca has half bound to albumin and other half is complexed w/ organic anions, phosphate, or free
. Measure of serum Ca used to measure ionized Ca
. Ca-sensing receptor is assoc. w/ PTH secreting cells
Hypercalcemia
. Common metabolic emergency
. Primary hyperparathyroidism from parathyroid adenomatous and cancer
Hypocalcemia
. Due to hypoparathyroidism due to surgical removal
. Hypoalbuminemia, hyperphosphatemia, and vit. D deficiency/resistance
Vit. D related disorders
. Leads to altered Ca and PO4metabolism
. Manifest as rockers
Magnesium
. 25g in human Boyd w/ over half found in teeth
. Functions in charge neutralization (stabilize polyphosphateS)
. Bind to induce activation or stabilize active conformation of enzymes
Mg deficiency
. Symptoms non-specific (neuromuscular issues, cardiovascular problems, anorexia, nausea, personality changes)
. GI disorders and renal loss can cause this
Mg toxicity
. Due to excessive intake of Mg salts (antacids, laxatives) esp. when combined w/ renal insufficiency
. Nonspecific symptoms: hypotension, vomiting, cardiac arrhythmias, muscle weakness, hyporeflexia
zinc
. 1.5 mg in girls, 2.5 in boys
. Mainly in skeletal mm. And bone
. Essential for growth and reproduction, wound healing, taste sensation, and immune function
. Plays catalytic/structural role in over 200 enzymes, stabilization of biomembrane, component of Zn-finger proteins (TFs)
. Dietary sources: shellfish, beef, and other red meat, fortified cereal (attached to physic acid and prevents some absorption)
. RDA: 15 mg men and 12 for women
Metallothionein
. Cys-rich protein which binds Zn is important mediator of Zn absorption
. When Zn intake is high, metallothionein synthesis in intestinal cells inc. and less Zn is released into portal circulation
. When intake is low, less is synthesized and more Zn is released into circulation
. Also binds to copper
Zn deficiency
. Uncommon
. Occurs in patients w/ acrodermatitis enteropathica (rare genetic disease causing dec. Zn absorption)
. Causes: patients w/ Fe/Cu overload, anticonvulsant drugs, pregnancy, elderly, and diarrhea
Clinical manifestations of Zn deficiency
. Delayed growth, sexual maturation, impotence . Hypogonadism and hypothermia . Alopecia . Acroorificial skin lesions . Delayed wound healing . Immune dysfunction . Impaired taste and appetite . Eye lesions . Behavioral abnormalities
Zn toxicity
. Rare
. Similar to Cu deficiency symptoms, dec. HDL-C, gastric function, and impaired immune function, may result from long-term ingestion of Zn supplements
Copper
. Important for Cu-containing compounds, erythropoesis, and erythrocyte function, platelet function, lipoprotein metabolism, cardiac function, and immune function
. Sources: organ meats, shell fish, nuts, seeds, legumes, chocolate
. Daily intake 1.5-3 mg
Copper absorption and transport
. Occurs in SI and is inc. or dec. based on Cu intake
. Cu enters portal circulation and is transported to liver for incorporation into Cu-containing compounds (ceruloplasmin protein in blood)
Cu deficiency and toxicity
. Premature babies, babies fed cow’s milk, patients w. Malabsorption issues, patients using high dose zinc supplements, patients receiving long-term parenteral nutrition support
Menkes’ disease
. Rare x-linked disease
. Caused by mutation in ATP7A gene
. Causes impaired absorption of Cu from diet and a lethal copper deficiency (death by age 3)
Wilson’s disease
. Autosomal recessive disease caused by mutation in ATP7B gene
. Leads to impaired Cu excretion in bile
. Massive deposition of Cu in liver and other organs leading to Cu toxicity
. Treatment: chelation therapy
Selenium
. Essential component of selenoproteins that function in antioxidant detoxification, thyroid hormone metabolism, and regulation of cellular redox status
. Co-translational incorporation of selenocysteine into proteins is facilitated via stem-loop structure in mRNA facilitating read through of UGA as selenocysteine
. Sources: organ meats, seafood, Brazil nuts, meat and poultry, some plant foods
Other essential minerals
. Molybdenum
. Manganese
. Chromium
. Ultra traces minerals (boron, silicon, nickel)