Viewing All Flashcards for Biochem - 3 - Minerals
Minerals may be divided arbitrarily into 2 groups: Macrominerals (required in amounts greater than 100 mg/day) and microminerals - trace elements (required in amounts less than 100 mg/day).
Absorption is rarely complete. It is affected by other nutrients and compounds in the diet. Oxalates and phylates chelate divalent cations (for example, phytate from spinach prevents the absorption of iron). Transport and storage also require special proteins.
Excretion occurs in the feces (unabsorbed minerals and from bile) and urine and sweat.
Toxic symptoms. Unless otherwise specified, symptoms include non-specific nausea, diarrhea, and irritability.
By a varied intake of adequate amounts of whole-grain cereals, legumes, leafy vegetables, meat, and dairy products.
Constituent of bones, teeth, and regulation of nerve, muscle function.
Calcium-binding protein (calbindin D28K).
Vitamin D, parathyroid hormone, and calcitonin.
The formation of 1,25-dihydroxycholecalciferol, which enhances intestinal calcium absorption and, with parathyroid hormone, stimulates bone resorption.
It almost always results in net loss of calcium from bones.
Ionized calcium (47%), albumin-bound (40%), and complexed to phosphate and citrate (13%). A total serum calcium includes all of these forms.
Ionized calcium is metabolically active and has a negative feedback with parathyroid hormone. Ionized calcium maintains the normal muscle and nerve threshold potential.
There is an increase in negative charges on albumin, because there are fewer H+ ions and more COO- groups on the acidic amino acids (aspartate, glutamate). Therefore, proportionately more calcium is bound to albumin at the expense of the ionized calcium concentration.
No, however it does lower the ionized calcium level, resulting in a lowering of the muscle and nerve threshold potential, which causes tetany.
PTH and thiazide diuretics.
It resembles those of vitamin D deficiency. Rickets in children, osteomalacia in adults, high protein diets promote calcium excretion in urine and could promote kidney stones.
Excess absorption due to hypervitaminosis D, hypercalcemia due to hyperparathyroidism, idiopathic hypercalcemia.
Dairy products, beans, leafy vegetables.
Vitamin C is needed to form the bone matrix and magnesium and phosphorus are important components of the bone structure. Vitamin K and a variety of trace minerals, including copper, zinc, manganese, and boron, are important for bone formation. Thus, calcium supplements may not be optimally utilized if the overall diet is inadequate.
Constitutent of bones, teeth, ATP, nucleic acids, phosphorylated metabolic intermediates.
Unknown. Maybe vitamin D.
Synthesis and stores of 2,3-bisphosphorglycerate (BPG).
Hemoglobin releases its oxygen more easily and as a result, the hematocrit and HB values are set lower.
Rickets in children and osteomalacia in adults.
Low serum Ca:P ratio stimulates secondary hyperparathyroidism which may lead to bone loss.
Phosphate food additives.
Reabsorption: 70% (proximal tubule), 15% (thick descending limb). Excretion: 15%.
Principal cation in extracellular fluid. It regulates plasma volume, acid-base balance, nerve and muscle function, Na+/K+-ATPase.
It is a potent neurotoxin with no known antidote. Tetrodotoxin binds to what is know as site 1 of the fast voltage-gated sodium channel. Tetrodotoxin blocks action potentials in nerves by binding to the voltage-gated, fast sodium channels in nerve cell membranes, essentially preventing any affected nerve cells from firing by blocking the channels used in the process.
Unknown on normal diet. Secondary to injury or illness.
Hypertension (in susceptible individuals).
Table salt, salt added to prepared food.
Principle cation in intracellular fluid. Nerve and muscle function, Na+/K+-ATPase.
The secretion of aldosterone.
Occurs secondary to illness, injury, or diuretic therapy. Muscular weakness, paralysis, mental confusion.
Vegetables, fruits, and nuts.
Fluid and electrolyte balance, gastric fluid.
Secondary to vomiting, diuretic therapy, renal disease.
Constituent of bones, teeth. Enzyme cofactor for many enzymatic activities utilizing ATP-Mg2+ (example: kinases).
Secondary to malabsorption or diarrhea, alcoholism. The main symptoms are weakness, tremors, and cardiac arrhythmia.
Depressed deep tendon reflexes and respiration.
Leafy vegetables (containing chlorophyll).
May help prevent formation of calcium oxalate stones in the kidney.
Kanamycin, streptomycin, neomycin, and gentamycin.
They are a common cause of magnesium wasting in the urine leading to hypomagnesemia.
PTH and also controls the synthesis and release of PTH.
To allow fusion of the secretory granules with the membrane in order to release PTH.
Deficiency of magnesium produces a functional hypoparathyroidism with a concomitant decrease in serum calcium, leading to hypocalcemia.
It lowers it so that it is closer to the resting membrane potential. This leaves muscles and nerves in a partially depolarized state and subject to the clinical findings of tetany (ex. thumb adduction into the palm with blood pressure measurements).
Proximal tubule (30%), thick ascending limb (60%), distal tubule (5%). Excretion - 5%.
Constituent of chromodulin, "glucose tolerance factor", which potentiates the effects of insulin by facilitating both the insulin binding to its receptor and the receptor kinase signalling.
Impaired glucose tolerance is the chief symptom of deficiency, a result of decreased insulin sensitivity. Diabetes causes increased urinary loss of chromium, that over time can lead to deficiency. Supplementation with chromium appears to improve glycemic control in patients with diabetes type 2.
Meat, liver, whole grains, nuts, and cheese.
Required only as a constituent of vitamin B12, therefore its metabolism and deficiency states are as those for vitamin B12.
Dietary iodine is efficiently absorbed and transported to the thyroid gland. In the thyroid gland, it is utilized for the synthesis of T3 and T4. These hormones function in regulating basal metabolic rate of adults and in the growth and development of children.
It is stored in the thyroid gland as thyroglobulin and requires proteolytic activity to release the hormone from thyroglobulin.
Cretinism in children (person that is deformed and mentally handicapped). Physical examination reveals a pot-bellied, pale child with a puffy face. The child's tongue is enlarged. It is due to congenital deficiency of thyroid hormones. Goiter (enlargement of the thyroid gland, sometimes massive) and hypothyroidism in adults. In Graves disease, which is the most common form or cause of hyperthyroidism, the eyes may look enlarged because the upper lids are elevated. Sometimes, one or both eyes may bulge. Some patients have swelling of the front of the neck from an enlarged thyroid gland (a goiter).
Constituent of heme (hemoglobin, cytochromes, etc.).
Plasma ferritin has a half life of 50 hours, is cleared by reticuloendothelial cells and hepatocytes, and its concentration, although very low, correlates closely with the size of the body iron stores.
It is deposited on the outside of ferritin in an amorphous mixture of iron phosphate, iron hydroxide, and proteins called hemosiderin in the liver, pancreas, and pituitary, leading to organ failure.
In sloughed cells and by bleeding.
Deficiency in iron, copper, or pyridoxine.
Deficiency in vitamin B12, folate.
Iron is absorbed in the diet, transported in the blood by transferrin, stored in ferritin, and used for the synthesis of cytochromes, iron-containing enzymes, hemoglobin, and myoglobin. It is lost from the body with bleeding, sloughed-off cells, sweat, urine, and feces. Hemosiderin is the amorphous iron deposition adjacent to ferritin spheres.
Iron uptake and delivery to the bloodstream by the intestine.
DMT-1 expression is up-regulated and ferritin expression is down-regulated. In addition, hepcidin expression is down-regulated, this results in stabilization and accumulation of ferroportin.
Several other transition metals that occurs naturally in the 2+ state, such as zinc, copper, and manganese.
It is oxidized to the Fe3+ state by two ferroxidases called hephaestin and ceruloplasmin. Both are involved in the oxidation but hepatocytes and macrophages use ceruloplasmin exclusively.
Copper. This is thought to be the reason that anemia is a symptom of copper deficiency.
Transferrin levels are increased under conditions of iron deficiency and decreased under conditions of iron excess, but transferrin levels are generally in excess so this effect is much less important than the regulation of the other proteins.
The protein homojuvelin (HJV), transferrin receptor 2 (TfR2) and the major histocompatibility class 1 like molecule (HFE).
It is up-regulated. Mutations in any of these proteins can lead to an iron overload disease called hemochromatosis because hepcidin is not available to downregulate ferroportin under conditions of iron excess.
Results in an increase in hepcidin levels via the effects of cytokines such as interleukin 6 (IL-6). This results in sequestration of iron in tissues and reduces the risk of systemic infections.
is taken up by binding to the transferrin receptor (TfR1). The
transferrin-receptor complex clusters in clathrin-coated
pits and is taken up by endocytosis.
the interior of the endosome is acidified, Fe3+ is
released from transferrin and reduced by a ferrireductase
called streap3, the resulting Fe2+ is
transported into the cytosol by DMT-1.
Fe2+ is transported into the
mitochondria by mitoferrin and
inserted into protoporphyrin IX
to form the heme by
the enzyme ferrochelatase
Ferritin is the major protein involved in storage of iron. Transferrin, a B1-glycoprotein synthesized in the liver, is the protein in serum involved in the transport of iron. The transferrin receptor is a transmembrane protein in the surface of the cells that bind plasma transferrin. The receptor-transferrin complex is internalized into the lysosome where the iron is released.
Anemia (hypochromic, microcytic). Common causes for iron deficiency are excessive menstrual flow, multiple births, and gastrointestinal bleeding that may be occult.
Iron overload (siderosis) is due to a mutation in the human hemochromatosis protein also know as the HFE protein. This is a protein which in humans is encoded by the HFE gene (autosomal recessive genetic disorder). Unusually, the official gene symbol (HFE for High Iron) is not an abbreviation of the official name (hemochromatosis). Its primary mode of action is then through regulation of the iron storage hormone hepcidin.
Accumulation of iron in the liver, pancreas, and heart that can lead to cirrhosis and liver tumours, diabetes mellitus, and cardiac failure.
A certain group of patients acquire excess iron because they ingest large amounts of both iron and ethanol, the latter promotes iron absorption.
A bacterial siderophore produced by the actinobacter Streptomyces pilosus. It has medical applications as a chelating agent used to remove excess iron from the body.
Constituent of oxidase enzymes (ex. cytochrome C oxidase), cytosolic superoxide dismutase, dopamine B-hydroxylase (norepinephrine synthesis), lysine oxidase (collagen cross-linking), C18, triangle 9-desaturase that converts stearic acid to oleic acid. This may explain why dietary stearic acid does not raise blood cholesterol like the other saturated fatty acids. Copper also plays a role in iron absorption. Ceruloplasmin contains copper and oxidizes iron from Fe2+ to Fe3+ to facilitate binding to transferrin.
A high-affinity copper transporter called CTR1.
ATP-7A and ATP-7B. ATP-7A is found in every tissue and is essential for exit of copper from intestinal cells. ATP-7B is found in greatest abundance in liver and brain and is responsible for exit of copper from those tissues.
Intracellular copper concentrations. When the intracellular copper concentration is low, both ATP-7A and 7B are localized primarily within the trans Golgi network. When intracellular copper levels are high, ATP-7A is transferred to the basolateral plasma membrane surface of the intestinal mucosa for transport of copper into the bloodstream. ATP-7B is transferred to the bile canaliculus for excretion of copper into the bile.
Menkes syndrome. It is relatively rare and is usually seen due to excess zinc intake (zinc and copper compete for absorption), includes anemia, hypercholesterolemia, demineralization of bones, fragility of large arteries, and demyelination of nerve tissue. Copper deficiency is also observed in the Menkes' syndrome, a relatively rare X-linked hereditary disease associated with a defect in ATP-7A, which affect the transport of copper from intestinal cells into the bloodstream and causes a global copper deficiency.
Mental retardation, hypothermia, loose skin and joints, hypopigmentation, and kinky hair, which are caused by the inability to load copper-dependent enzymes with copper.
An autosomal recessive disease, characterized by copper overload, particularly in liver and brain.
It is caused by mutations of ATP-7B gene that prevent the liver and brain from removing excess intracellular copper levels. The accumulation leads to cirrhosis, and liver failure while in the brain leads to parkinsonian-like symptoms. Copper also accumulates as a characteristic gold brown ring, called the Kayser-Fleischer ring around the periphery of the cornea. Treatment consists of restricting copper in the diet and prescribing the copper chelator penicillamine, to excrete the copper from the body.
part of the catalytic center of over 300 metalloenzymes
including RNA and DNA polymerases, alkaline phosphatase, and carbonic anhydrase
addition, there are problems with wound healing, since zinc is a coenzyme for
collagenase. Collagenase is important in remodeling a wound, which involves the
replacement of type III collagen with type I collagen, the latter having
greater tensile strength
of zinc fingers motifs that provide structural stability to DNA binding
proteins (example : in transcription factors, nuclear receptors for
binds to the metal response element (MRE) of MRE-binding transcription factor-1
(MRF-1) and control gene expression similarly to the effect of iron on binding
of IRPs to IREs
containing enzyme, porphobilinogen
synthase is affected by lead poisoning
Reactions associated with maintenance of skin and mucosal integrity, wound healing, spermatogenesis, and growth in children.
In alcohol abuse, rheumatoid arthritis, and acute and chronic diseases.
Clinical findings include problems with taste (dysgeusia) and smell (anosmia) and development of an acneiform rash on the face. In addition, there are problems with wound healing, since zinc is a coenzyme for collagenase. Collagenase is important in remodeling a wound, which involves the replacement of type III collagen with type I collagen, the latter having greater tensile strength.
Acrodermatitis enteropathica, parenteral nutrition.
Gastrointestinal irritation and vomiting.
Cofactor of hydrolase, decarboxylase, and transferase enzymes. Glycoprotein and proteoglycan synthesis. Mitochondrial superoxide dismutase.
Deficiency: Unknown. Toxicity: Inhalation poisoning produces psychotic symptoms and parkinsonism.
Constituent of oxidase enzymes (xanthine oxidase). Xanthine oxidase is also a dehydrogenase under low concentrations of purine. Under those conditions, NAD is used as the acceptor of electrons. When xanthine oxidase has high concentrations of purine to be oxidized, for example when the levels of AMP are high in the cells, oxygen is used as the acceptor electrons to produce hydrogen peroxide.
Constituent of glutathione peroxidase.
Synergistic antioxidant with vitamin E.
Marginal deficiency when soil is low. Secondary to parenteral nutrition, protein energy malnutrition.
Toxic levels in some soil. Megadose supplementation induces hair loss, dermatitis, and irritability.
Plants, but varies with soil content; meat.
Essential for rat growth but not proved to be strictly essential for human nutrition.
Increases hardness of bone and teeth.
Dental caries. Streptococcus mutants, found in dental plaque, produces acids from the metabolism of carbohydrates. Topical fluoride treatment in the dental office can slow the production of acids. Fluoride inhibits the glycolytic enzyme enolase, which catalyzes the dehydration of 2-phosphoglycerate to PEP.