metab 2 EXAM 3

Magnesium's Role in Stabilizing Chemical Compounds

Magnesium binds to the phosphate groups of ATP to stabilize and activate the structure. This structural stability is especially important for kinase reactions, such as glucose to produce glucose-6-phosphate.

Potassium

Major intracellular cation

MAGNESIUM

Mg

Magnesium Functions and Mechanisms of Action

Mg is a cofactor for over 300 enzymes involved with metabolism, cholesterol synthesis, and DNA/RNA; especially for systems depending on ATP! Mg is needed for the hydroxylation of vitamin D. Mg deficiency leads to decreased parathyroid function and reduced 1,24 (OH)2 cholecalciferol. Mg is found in bone tissue. Mg is associated with the membranes of phospholipids, proteins, nucleic acids, and ATP. Mg stabilizes ATP.

Osmosis

Movement of water across semipermeable membrane in response to differences in solute concentrations

PHOSPHORUS

P

RXR

Retinoic acid X Receptor

Electrogenic Na+ absorption

Sodium enters the luminal membrane via a Na+ channel diffusion inwardly by the downhill concentration gradient of the ion. The absorbed sodium is accompanied by water and anions, resulting in net water and electrolyte moment from the luminal side to the basolateral side of the cells. Sodium is pumped out across the basolateral membrane by the Na+/K+ ATPase pump which maintains a low intercellular Na+ concentration and creates the electrical gradient. This is more common in the colon.

Absorption of Sodium

Sodium has a 90-95% absorption rate. Excretion is controlled by the kidneys as the primary method of physiological regulation. Sodium absorption mechanisms: - Na+/glucose cotransport system - Na+/Cl- cotransport system - Electrogenic Na+ transport Sodium is also involved in the transport of certain amino acids, dipeptides, tripeptides, and some of the water-soluble vitamins across the apical membrane of enterocytes in a mechanism similar to the Na+-glucose co-transporter.

Sodium, Chloride, and Potassium Facts

Sodium is a positive cation in ECF. Potassium is a positive cation in ICF. Chloride is an anion in ECF. Two main physiological purposes: 1. Water balance across cellular membranes 2. Electrolyte potential across plasma membranes These elements are often referred to as electrolytes because of their ability to conduct an electric charge.

Osmolarity

Solute (particle) concentration of a fluid

Electroneutral Na and Cl absorption

The sodium-hydrogen exchange. Works in concert with a Cl-/HCO-3 exchange. This transporter allows the entrance of both Na and Cl into the cell, where they are exchanged for the H+ and HCO-3., respectively. Protons (H+) and HCO-3 are produced within the cell by the action of carbonic anhydrase on CO2. Sodium is then pumped basolaterally with Cl- diffusing passively, mostly paracellular.

Regulation of Iron Uptake by Hepatocytes Through the Transferrin Receptor

The transferrin receptor with bound transferrin is engulfed by the cell, and iron is reduced from the ferric to the ferrous form so that it can be subsequently delivered to ferritin. In ferritin, iron is in the ferric form. Hemosiderin is a breakdown product of ferritin.

How Vitamin D Exerts Its Actions on Genes

The vitamin D receptor (VDR) acts in partnership with the retinoic acid receptors (RXR) and binds to nucleotide base pairs called the vitamin D-responsive elements (VDRE) to control gene expression. Cis-retinoic acid and 1,25-dihydroxycholecalciferol are ligands that must be present to control gene expression.

Serum Phosphorus Level

Under homeostatic control in blood (usual range 2.5/4.5 mg/dL •Parathyroid hormone •1-25 (OH)2 cholecalciferol Two specific proteins also produced to •Parathyroid Hormone (PTH) •Fibroblast Growth Factor 23 (FGF 23) - Produced by bone osteocytes •Klotho - Produced by a variety of tissue, including renal tubules

Iron Interactions with Other Nutrients

Vitamin C enhances iron absorption Copper - Deficiency results in iron-deficiency anemia Zinc inhibits iron absorption when taken together in supplements Vitamin A has several interactions Lead is a particularly pernicious element to iron metabolism, as it is taken up by the iron absorption machinery, and secondarily blocks iron through competitive inhibition. Furthermore, it interferes with a number of important iron dependent metabolic steps such as heme biosynthesis.

VDR

Vitamin D Receptor

Osteomalacia

Vitamin D deficiency in adults. This results from decreased calcium and phosphate absorption. Loss of mineral resulting in decreased bone density

Vitamin D reaching the liver either by way of chylomicron remnants or by DBP

must be hydroxylated by cytochrome P-450 hydroxylases to begin the generation of vitamin D's active form. These hydroxylases are collectively referred to as mixed-function oxidases (the enzymes reduce one atom of molecular oxygen to water and one to the hydroxyl group). They are abbreviated as CYP followed by numbers and letters. In the liver, 25-hydroxylase (NADPH-dependent), function in the mitochondria to hydroxylate vitamin D3 at carbon 25 to form 25(OH)D. Another 25-hydroxylase found in the microsomes also hydroxylated vitamin D3 as well as D2. It is not until hydroxylation at C-25 in the liver and C-1 in the renal cells lining the proximal tubule that the active form of vitamin D, 1,25-dihydroxycholcalciferol [1,25-(OH)D3] is produced.

Hyponatremia (low Na+ concentration)

overhydration, cell swelling, plasma diluted due to increase in water no change in solutes. - hypotonic •Diluted plasma due to overconsumption of water •Cause: diarrhea, heart failure, liver and renal disease

Hyperkalemia

a serum or plasma potassium level above the upper limits of normal, usually greater than 5.0 mEq/L to 5.5 mEq/L. While mild hyperkalemia is usually asymptomatic, high levels of potassium may cause life-threatening cardiac arrhythmias, muscle weakness or paralysis.

Ionized Mg is the

active form

Calcitriol

acts on cells in the GI tract to increase the production of calcium transport proteins, termed calbindin-D proteins, which results in increased uptake of calcium from the gut into the body This is the only mechanism by which the body can increase its calcium stores.

The efficiency of vitamin D binding is tremendously increased

after two hydroxylations to its molecular form.

7-dehydrocholesterol

provitamin found in human skin - enable humans to manufacture vitamin D3 from UV light. Also, found in breast milk

Vitamin D exerts most of its effects via

binding to a Vitamin D receptor (VDR) that interacts with DNA.

1α -hydroxylase

catalyzes the conversion of 25-OH D to 1,25-(OH)D3 (the most potent metabolite of vitamin D) found in renal cells lining the proximal tubule The activity of the enzyme is enhanced by PTH and IGF-1 and inhibited by calcium and phosphorous.

Ergosterol

converted to vitamin D2 when irradiated with UV light

Increased potassium intake leads to

decreased risk for elevated blood pressure

Major minerals

dietary need ≥ 100 mg/day and > 0.01% of total human mass •Calcium, phosphorus, sodium, potassium, chloride, magnesium, and sulfur

Hypotonic

has a lower osmotic pressure than another solution: has less solute and more water than another solution - more water less solute

Hypertonic

having a higher osmotic pressure than a fluid, typically a body fluid or intracellular fluid. - more solute less water

Isotonic

having the same osmotic pressure as some other solution, especially one in a cell or a body fluid

Calcium deficiency

increased PTH secretion leading to bone resorption •Osteomalacia (soft bones) •Osteoporosis (loss of total bone)

Hypernatremia (high Na+ concentration)

increased serum sodium, loss of water without solutes, cells shrink - hypertonic •Losses of water without solutes •Cause: diarrhea, drugs, blood pressure-lowering medication, high fevers, profuse sweating

Ergocalciferol

known as vitamin D2 or calciferol, found in food and as dietary supplement

Cholecalciferol

known as vitamin D3, made by the skin when exposed to light

inhibitors

magnesium and aluminum

MARRS

membrane associated, rapid response steroid binding

CALCIUM

most abundant divalent (have a valence of two (2+) cation in the body

Hypocalcemia

reduced PTH secretion and/or impaired vitamin D •Low blood calcium levels: muscle cramps, irritable nervous tissue, tetany, parestheia

functions of calcium

structural: Bone and teeth mineralization functional: •Nerve impulse transmission •Regulation of muscle contraction •Maintenance of acid-base balance (pH) •Regulation of biochemical reactions via calmodulin •Blood coagulation

Hypokalemia

when blood's potassium levels are too low Potassium is an important electrolyte for nerve and muscle cell functioning, especially for muscle cells in the heart. Your kidneys control your body's .potassium levels, allowing for excess potassium to leave the body through urine or sweat. Can cause heart arrythmia

digestion and absorption of Phosphorus

•Absorbed in the free inorganic form •Bound, organic molecules must be liberated by digestive enzymes (phospholipase C, alkaline phosphotase) Factors affecting absorption: •Absorption stimulated by vitamin D •Decreased phosphorus absorption with increased magnesium and calcium •Absorption decrease due to antacids

Magnesium Functions: Other roles

•Blood clotting •Anti-inflammatory role •Hormone receptor binding and activation of second-messenger signaling •Ion channel regulation •Antagonism of intracellular calcium •Insulin production, release, and action/signaling

associated factors with calcium deficiency

•Blood pressure: increased calcium, decreased blood pressure •Body fatness: decreased calcium, increased fatness

Phosphorus homeostasis

•Calcitriol enables phosphorus absorption in the intestine •Calcitriol promotes resorption of phosphorus out of bone and into blood

VITAMIN D

•D2 (ergocalciferol) •D3 (cholecalciferol) •Provitamin - 7 dehydrocholesterol

Electrolytes and Other Nutrients

•Diets high in sodium increase calcium excretion. •Diets high in potassium decrease calcium excretion. •Increased sodium intake results in increased risk for elevated blood pressure.

Absorption of Magnesium

•Does not require digestion •Entire small intestine and colon absorbs Mg through two methods - Active transporter: TRMP6 - Paracellular diffusion •25-60% absorption rate •Increased need, increased absorption •Factors affecting absorption: - increased by vitamin D - excess calcium, phosphorus, magnesium, phytates, or excessive fatty acids decrease Mg absorption.

Elevated serum phosphate:

•FGF23 reduces serum phosphate through its action on the kidneys by increasing excretion rate. This is down through downregulation of NaPi2 transporters in the kidneys. •FGF23 diminishes intestinal absorption by diminishing phosphate transporters and reduces 1a-hydroxylase activity. Calcitonin inhibits osteoclast activity and thus decreases bone resorption.

Functions of Vitamin D

•Functions due to Vitamin D receptor mediation •Regulation of gene expression •Differentiation of stem cells in bone tissue •Differentiation of hair follicles and skin cells •Possible roles in bone metabolism and/or bone formation and cancer prevention or treatment •Multiple sclerosis, type 1 diabetes, inflammatory bowel disease (ulcerative colitis and Crohn's disease), and rheumatoid arthritis •Thought to prevent heart diseases of various types

Ratio of Ca:Mg is critical to health

•Greater than 2.7 results in increased rectal adenomas •Less than 1.7 increases ischemic heart disease risk •Safe level is 1.7 to 2.7 For example, a diet of 1300 mg Ca and 300 mg Mg is a (750/300) is a 2.5 ratio of Ca:Mg. Supplemental doses of Ca may be as high as 2000-2500 mg/day with low or no added Mg. This would result in a ratio of 6.6 Ca:Mg (2000mg /300 mg).

factors that INCREASE calcium absorption

•Healthy vitamin D intake •Acidic conditions in the GI tract •Lactose •Lack of stress •Calcium distribution throughout the day •Increased need

Idiopathic hypercalciuria (and fat malabsorption disorders)

•High urinary calcium (250-300 mg/day) •Increased susceptibility to kidney stones

Hydroxylation Reactions of Vitamin D of Biological Significance

•Hydroxylation in the liver and renal cells - active form of vitamin D, 1,25-dihydroxycholcalciferol [1,25-(OH)D3] is produced

Vitamin D is unique because

•Is synthesized in the body with adequate sun exposure •Functions as a hormone

functions of sodium

•Maintenance of osmotic pressure •Nerve transmission/impulse conduction •Muscle contraction •Dietary sodium intake increases urinary calcium excretion

Vitamin D Metabolism, and Storage

•Metabolized to 25(OH)D in liver •25-OH D secreted into blood, transported by DBP •Converted to 1,25-OH2 D (calcitriol) in kidneys - Calcitriol released into blood

Additional Iron Facts

•Multiple factors increase and decrease absorption. •Iron is part of heme structures. •Iron uptake is regulated by liver cells through the transferrin receptor. - Vitamin C intake plays a significant role in iron absorption. Quite simply, as vitamin C intake increases in conjunction with iron-containing sources, iron absorption is enhanced. It is likely that vitamin C promotes the formation and stabilization of ferrous iron, which , as mentioned earlier in the semester, is much better absorbed than the ferric form. - Living at high altitude appears to create a greater need for iron. Therefore, greater iron absorption is needed to synthesize more red blood cells under the control of erythropoietin.

factors that DECREASE calcium absorption

•Oxalates, phytates, and fiber in food •Rapid GI tract movement •Very high fat diet or decreased fat digestion •Excess vitamin A •Excess phosphorus, magnesium and zinc •Decreased physical activity

Low serum phosphate

•PTH and Calcitriol: resorption from bone •Calcitriol: increased small intestine absorption and kidney reabsorption

functions of potassium

•Proper intercellular to extracellular ratio needed to maintain cell's resting membrane potential •Water and acid-base balance •Needed for cellular metabolism •Decreases urinary excretion of calcium

Calcitriol synthesis

•Stimulated in response to changes in serum calcium concentrations and the release of PTH •Hypocalcemia (less than 8.5 mg/dL) PTH stimulates calcitriol production in the kidney by increasing the synthesis of 1-α hydroxylase. Calcitriol has several important functions in the body. It maintains serum calcium levels by increasing calcium absorption in the GI tract. Calcitonin has the opposite effect - It decreases the amount of calcium and phosphate in the blood.

functions of phosphorous

•Structure to cellular membranes •Mineralization of bones and teeth •pH regulation of ECF •Nucleic acid formation (Part of DNA and RNA) •Acid base balance -acts as physiological buffer •Inositol phosphate - Causes Ca release from organelles in cells - Activates kinases in cells

Sources of Vitamin D

•UV light •Animal foods (eggs, liver, fatty fish, and butter) •Fortified milk and dairy products; Fortified margarine

Water (Fluid) and Sodium Balance

•Water movement strongly affected by sodium in ECF - Movement between interstitial space and extracellular space regulated by osmotic pressure •Movement across capillary blood vessel walls that separate plasma from interstitial space - Governed by differences in hydrostatic pressure and colloidal osmotic pressure

Blood calcium levels are tightly regulated by several endocrine factors

- PTH (stimulates increase of calcium absorption) - Vitamin D3 (calcitriol) stimulates production of calcium binding protein and intracellular calcium binding protein - calbindin (calcium absorption) - calcitonin (increases calcium deposition removing it from the blood)

The Role of Iron-Responsive Element-Binding Protein (IREP) in the Regulation of Iron Storage Proteins

In iron deficiency, IREP is active and blocks ferritin transcription but stabilizes the mRNA of the transferrin receptors. When iron levels are high, iron binds to the IREP, thereby preventing it from binding it to the mRNA for either protein.

Calcium-alkali syndrome

Ingestion large amounts of calcium carbonate salts to prevent or treat osteoporosis or dyspepsia

Several factors decrease iron absorption

-High phytic acid intake -Polyphenolic substances, such as tannins in tea, oxalates in spinach, chard, berries, chocolate, teas, and other foods; phytate in whole grains; and the preservative EDTA by chelation (binding of ions and molecules to metal ions) -Supplemental doses of calcium and calcium in milk may decrease iron absorption - take iron supplements in the absence of a significant source of calcium -Zinc may also compete with iron for a common transporter and may decrease absorption

In blood, Calcium is found in three forms

1) ionized (Albumin is the primary transport protein) 2) bound to proteins 3) complexed with anions

Trace minerals

1-100 mg/day

process of absorption

1. Ca 2+ crosses the brush border membrane of the enterocyte through a calcium channel TRPV6. 2. Ca2+ binds to calbindin D, which carries the calcium across the cytosol of the enterocyte. 3. Ca2+-ATPase (PMCA1 b) or a Na+/Ca2+ exchanger (NCX1) pump calcium across the basolateral membrane for entrance into the blood. 4. Some Ca2+ is absorbed between cells, typically with high Ca2+ concentrations in the lumen.

Calcium Balance as Mediated by Parathyroid Hormone (PTH), Calcitonin, and Vitamin D (25-OH)

1. Low blood calcium signals the parathyroid gland to release parathyroid hormone (PTH) into the blood. 2. PTH binds to bone cell receptors and triggers the resorption or breakdown of bone mineral for the release of calcium into the blood. 3. PTH acts on the kidneys to synthesize the active form of vitamin D, calcitriol. 4. PTH and calcitriol promote the reabsorption of calcium from the kidneys and into the blood. 5. Calcitriol leaves the kidneys and travels to the intestine, where it promotes calcium absorption across the brush border membrane, its transport in the cell cytosol, and egress into the blood. 6. Calcium enters the blood a) after release from bone, b) after release from kidneys, and c) after absorption from intestinal cells.

process

1. Mg2+ crosses the brush border membrane of the enterocyte through a magnesium channel, TRPM6. 2. Mg2+ also may be absorbed between cells; this transport is influenced by the electron chemical gradient and solvent drag. 3. Mg2+ is pumped out of the cell across the basolateral membrane by a sodium-dependent ATPase.

Ultratrace Minerals

< 1 mg/day

Na+/glucose co-transport

A carrier on the brush border membrane of the enterocyte cotransports sodium together with a solute such as glucose or other nutrients, such as amino acids and some B vitamins into the cells. They both are released before the carrier returns to the cell membrane. Once in the cell, sodium is pumped across the basolateral membrane by Na/K -ATPase, glucose exits through the membrane by facilitated diffusion. The Na+ gradient is created by the energy needed to maintain the absorptive direction of the ion.

Potassium absorption

Absorbed by passive diffusion or by a K+/H+-ATPase - the colon being a major site of absorption Stimulated by insulin Extracellular potassium is necessary for the movement of sodium across the basolateral membrane as well because it is used in the Na+-K+ ATPase antiport system.

Recommended Water Intake

Adequate Intakes: •Adult women: 2.7 L (91 oz): 8 cups/day •Adult men: 3.7 L (125 oz): 12 cups/day Large variation in individual needs based on activity level and energy intake •25-40 mL of water per kg body weight

calcium supplements

Avoid single large doses - better absorbed when distributed throughout the day

Calcium Digestion and Absorption

Calcium must be liberated from food to be absorbed (i.e., in its free state). Two mechanisms: 1) Through cells - Saturable, active mechanism requiring calcitriol - Requires membrane calcium channel TRPV6 to enter enterocyte - Binds to Calbindin9k in cell - Export to the blood via PMCA or NCX transp. 2) Between cells (paracellular)

Intestinal Chloride Secretion

Chloride follows sodium - Na+/glucose cotransport system: chloride follows actively absorbed Na+ - Electroneutral Na+/Cl- cotransport absorption: chloride absorbed in exchange for bicarbonate as sodium is absorbed in exchange for H+ - Electrogenic Na+ absorption: chloride follows the absorbed sodium passively Chloride is absorbed along the length of the small intestine, and its absorption is often associated with sodium absorption in efforts to maintain electric neutrality. With the exception of NaCl co-transporter mentioned earlier, most chloride absorption occurs in a paracellular manner because chloride appears to navigate between tight junctions between enterocytes.

Facts About Minor Minerals

Deficiency from dietary lack or malabsorption - Symptoms: fatigue, lethargy, decreased ability to make ATP by aerobic mechanisms, decreased iron-containing enzyme activity

Electrolytes

Distributed throughout fluid compartments Electrolytes: for example in the blood plasma, maintain electric neutrality. With the anion concentration balanced by the cation concentration.

ECG Changes with potassium imbalance

ECG should be done on patients with hypokalemia. Cardiac effects of hypokalemia are usually minimal until serum potassium concentrations are < 3 mEq/L. Hypokalemia causes sagging of the ST segment, depression of the T wave, and elevation of the U wave. Early ECG changes of hyperkalemia, typically seen at a serum potassium level of 5.5-6.5 mEq/L, include the following: Tall, peaked T waves with a narrow base, best seen in precordial leads. Shortened QT interval. ST-segment depression. Although it is much less common than hypokalemia, hyperkalemia is much more dangerous, and when unrecognized or untreated it may result in cardiac arrest. Hyperkalemia is generally caused by decreased or impaired renal excretion, the addition of potassium to the extracellular space or transmembrane shifts of potassium.

Regulating serum phosphorus levels

Low Serum Phosphate •Parathyroid Hormone (PTH) •Calcitriol Elevated Serum Phosphate •Fibroblast Growth Factor 23 (FGF 23) •Calcitonin •Klotho

Role of Parathyroid Hormone in the Homeostatic Control of Calcium Through Interaction with Vitamin D Metabolism

Low blood calcium increases secretion of PTH. PTH stimulates (1) calcium release from bone; (2) 1 α-hydroxylase to produce 1,25 (OH)2D3 and (3) the reabsorption of calcium by the kidney tubules. 1,25 (OH)2 will enhance calcium absorption by stimulating small intestinal cells to produce the calcium uptake protein, calbindin. These series of reactions maintain calcium levels within a normal range.

Serum Calcium Homeostasis

Effects on kidneys, small intestine, and bone Hypocalcemia will trigger PTH release. PTH release will stimulate the release of calcium from bone. PTH will have two effects on the kidneys: 1) it will stimulate 1α -hydroxylase to produce 1,25-(OH)D3 and 2) it will stimulate the reabsorption of Ca by the kidney tubules. The 1,25-(OH)D3 will be released to the blood and target the small intestinal cells to stimulate the production of calbindin, which is a calcium uptake protein. Collectively, all of these reactions will raise blood calcium levels to a normal physiological range.

Unique Functions of Electrolytes

Electrolytes are involved in the production of electric potential across plasma membranes—this is important in muscle cells and neurons. Chloride is a component of HCl acid, which helps maintain electrical neutrality in the GI tract.

Sodium Excretion and Deficiency

Excreted by kidneys and sweat - Aldosterone controls excretion Deficiencies are rare - May occur with excessive sweating Chronic excessive sodium has been linked hypertension and cardiovascular disease.

Rickets

Failure of growing bones to mineralize properly. This results in bowing of long, weight-bearing bones (children)

IRON

Fe

functions of chloride

Formation of gastric hydrochloric acid Released by white blood cells to help destroy foreign substances Exchange anion for HCO3- in red blood cells - chloride shift

Hemochromatosis

HFE gene mutation iron overload

Key Players in Iron Absorption

Heme carrier protein 1 (hcp1) Heme oxygenase Divalent metal transporter 1 (DMT1) Ferritin and mobiloferrin IREG1 of ferroportin Hephaestin Steap3 Hepcidin Hypoxia inducible factors (HIFs)

heme iron

Heme iron is present in meat, poultry, and fish and its absorption is greater than nonheme iron. In addition to hemoglobin, heme is found in myoglobin and the cytochromes.

functions of iron

Hemoglobin and myoglobin - Oxygen delivery Iron-storage proteins: ferritin and hemosiderin Cytochromes and other enzymes involved in the electron transport chain Monooxygenases and dioxygenases - Amino acid metabolism, carnitine synthesis, and procollagen synthesis Peroxidases - Antioxidant roles and thyroid hormone synthesis Oxidoreductases Other iron-containing enzymes Iron as a pro-oxidant

Role of the Liver Hormone Hepcidin in Iron Absorption

Hepcidin blocks iron absorption when iron stores are high/sufficient

Magnesium Deficiency

Hypomagnesemia metabolic effects •Decreased PTH, calcium, potassium, and calcitriol concentrations Muscular, cardiovascular symptoms Factors that contribute to deficiency •Inadequate intake, excess alcohol use, malabsorptive disorders, medications, •Uncontrolled diabetes and metabolic syndrome Heart disease develops more quickly if magnesium deficiency exists

Absorption of Heme Iron by the Gastrointestinal System

Iron containing heme must be liberated from associated protein structures. That occurs in the stomach and small intestine via the activity of proteases in digestive secretions. Heme, endowed with iron, then crosses the luminal barrier - it does this by binding to a carrier on the intestinal membrane called heme carrier protein (hcp1). This binds heme iron on the luminal side of the enterocyte. Heme iron enters the cell and the enzyme, heme oxygenase, liberates the iron in the ferrous form.

iron deficiency

Iron intake frequently inadequate in these population groups: •Infants/young children •Adolescents •Menstruating females •Pregnant women Deficiency progresses to iron-deficiency anemia •Treatment requires supplements

Gains and losses of fluids along with solutes

Isotonic imbalances - Hypervolemia (fluid overload) - Hypovolemia (severe dehydration); can cause hypovolemic shock

neonatal iron overload

Concerns: increased free radical activity associated with excess iron, especially unbound iron in the reduced ferrous form

Absorption of Nonheme Iron by the Gastrointestinal System

Inorganic or nonheme iron is released from food components by digestive secretions. If the iron is associated with a protein, proteases and HCl acid are necessary for its liberation. It is then transported into the enterocyte by divalent metal transporter (DMT1) can bind nonheme iron and then deliver it to either ferroportin or mobiloferrin. DMT1 transports ferrous iron only. Ferric iron must be converted to ferrous iron before it can be absorbed. A number of reductases on the intestinal cell membrane can reduce the ferric iron to the ferrous form prior to binding to DMT1 for absorption. If iron binds to mobiloferrin, the iron is delivered to the basolateral side of the enterocyte and given to the membrane IREG1, which is sometimes called ferroportin. IREG1 will absorb the ferrous iron from the enterocyte to the blood, where iron will be converted to the ferric form by hephaestin and subsequently picked up by transferrin for delivery to the liver. Hephaestin is a copper containing enzyme, This enzyme oxidizes the ferrous to the ferric form of iron so that it can be picked up by serum transferrin, because the ferrous form cannot bind to transferrin. Only a small portion of iron is absorbed, depending on total body status. Iron bound to ferritin in the ferric acid form will be eliminated as enterocytes are replaced.

In addition to dietary vit D, the body can produce vitamin D3 from 7-dehydrocholesterol (aka DHCR7)

It is made in the sebaceous glands and secreted onto the skin's surface, where it becomes incorporated into the skin's various layers, including the dermis and epidermis. The conjugated set of double bonds (5 to 7) found in the B ring of 7-dehydrocholesterol allows the absorption of specific wavelengths of light found in the UV range. Thus direct exposure to UVB photons penetrate into the epidermis and dermis, allowing 7-dehydrocholesterol in the plasma membranes of skin cells to absorb the photons; this event causes the B ring to open, forming previtamin D3 (precholecalciferol). The unstable double bonds in previtamin D3 are rearranged through a process called thermal isomerization (the molecules have exactly the same number of atoms, but the atoms have a different arrangement).

How does calcium play a role in muscle contraction and neuroexcitation?

Surrounding each myofibril (remember a myofibril is the portion of the muscle fiber that houses actin and myosin) is a system of tubules called the sarcoplasmic reticulum. The sarcoplasmic reticulum stores calcium and it is the regulation of calcium release that causes muscular contraction. The action potential arrives at the nerve terminal and causes the release of a chemical called acetylcholine. Acetylcholine travels across the neuromusclualr junction and stimulates the sarcoplasmic reticulum to release its stored calcium ions throughout the muscle. As calcium is released it binds with a protein called troponin that is situated along the actin filaments. Sliding filament theory states that this binding causes a shift to occur in another chemical called tropomyosin. Because these chemicals have a high affinity for calcium ions they cause the myosin cross bridges to attach to actin and flex rapidly. For contraction to continue the myosin cross bridges must detach, "recock" and reattach.

Calcium as a Second Messenger with Calmodulin Protein to Activate Enzymes

The binding of certain hormones to plasma membrane receptors results in the opening of the calcium channels and increases in the intracellular calcium concentration. Calcium is then able to bind with calmodulin, a protein with four calcium-binding sites. This creates a conformational change in the protein. The presence of this calmodulin-calcium complexes results in several cellular events, including the regulation of key enzymes: myosin light chain kinase (involved in smooth muscle contraction), phosphorylase kinase (activate phosphorylase - glycogen degradation), phospholipase A2 (hydrolyze fatty acids) , protein kinase C, phosphodiesterase. Regulation of key enzymes: •myosin light chain kinase •phosphorylase kinase •phospholipase •protein kinase C •phosphodiesterase

Isotonic imbalance

Water and solute increase or decrease together in equal volumes so that osmolarity remains normal. Causes include: An inadequate intake of water (i.e. an inability to respond to thirst will cause serum osmolality to increase and lead to cellular dehydration). Prolonged isotonic fluid losses (extracellular fluid will become hypertonic as compensatory mechanisms are exhausted).