TRACE ELEMENTS.pdf

Prof.Dr.M.Koray GÜMÜŞTAŞ Assoc.Prof.Dr. Karolin Yanar İUC-Cerrahpaşa MePistry Zinc (Zn) • oysters, meat, liver, wheat germ, pumpkin seeds, sunflower seeds, all grains, almonds and milk are zinc rich nutrients Functions of zinc related with involvement of enzymes structure • • • • • • • • • • Re...

Prof.Dr.M.Koray GÜMÜŞTAŞ Assoc.Prof.Dr. Karolin Yanar İUC-Cerrahpaşa MePistry Zinc (Zn) • oysters, meat, liver, wheat germ, pumpkin seeds, sunflower seeds, all grains, almonds and milk are zinc rich nutrients Functions of zinc related with involvement of enzymes structure • • • • • • • • • • Redox homeostasis (superoxide dismutase) Regulation of pH (carbonic anhydrase) Nonspecific aldehyde synthesis (alcohol dehydrogenase) Visual cycle and night vision (retinol dehydrogenase) Folate digestion (polyglutamate hydrolase) Protein digestion(carboxypeptidase A and B ) Phospholipid metabolism (phospholipase C) Hem synthesis (aminolevulunic acid dehydratase) Nucleic acid and nucleotide metabolism (DNA polymerase, RNA polymerase ) Taste (gustin) *Functions of zinc related with matrix metalloproteinases • MMPs initiate bone growth and remodeling • innate immunity, • wound repair, • angiogenesis, • tissue repair, • cell migration Other functions • Regulation of serotonin and norepinephrine content • Cellular adhesion • Sperm motility and vitality • The participation of zinc in hormone production • zinc finger Tetrahedral zinc atoms bind with histidine and cysteine residues of protein and form folded structures known as zing finger • Zinc finger play roles in transcriptional regulation, ubiquitin-mediated protein degradation, signal transduction, actin targeting, DNA repair, cell migration, tumorigenesis, cancer progression, metastasis, regulation of hormone such as free T4, thymulin, estrogen, testosterone, insulin, insulin like growth factor-1 • Daily zinc requirement is about 12-15 mg, Max; 50mg • 15-30% of ingested zinc absorbed in duedenum and upper jejenum • Intestinal Zn2+ is absorbed by carrier mediated transport and diffusion • It is carried with Albumin (%60-70)and α2-macroglobulin(30- 40%) in plasma • It is bind to metallothionein and stored that form in tissues • It is excreted by sweat, feces and urine ACRODERMATITIS ENTEROPATICA • A rare cause of impaired zinc absorption from the intestine. • A severe zinc deficiency in which whole body zinc stores are depleted • is an autosomal recessive inborn error that occurs mutation of the zip encoding gene (ZIP4) on chromosome 8q24 toxicity • Zinc is relatively nontoxic. • Gastrointestinal system tract symptoms, decrease in heme synthesis and hyperglycemia have been observed in excessive (1gram) or repetitive doses exposure of zinc for several months. • Heme synthesis is decreased due to effects of excessive zinc concentration on copper metabolism. • Excessive zinc exposure produces some symptoms as abdominal and epigastric pain, bloody diarrhea, nausea and vomiting, metallic taste, decreased immune function, alteration in copper and iron metabolism in acute conditions. • In chronic conditions it may lead to copper deficiency, numbness, weakness, ataxia, and spastic gait, sideroblastic anemia, neutropenia and hyperglycemia • Excessive levels of intracellular zinc may play a role in cellular toxicity. Ischemia-reperfusion injury and Alzheimer’s disease are related to excessive zinc levels. • Increased intracellular levels of zinc results in loss of mitochondrial membrane potential, generation of free radicals, cell death and inhibition of α -ketoglutarate dehydrogenase complex Copper • Copper- rich dietary sources are liver, kidney, shellfish, nuts, raisins, egg yolk, whole grain cereals, cacao containing products, and legumes • RDA 900 µg/day for adult *Copper is core part of copper- containing enzymes which terms as cuproenzymes Cuproenzyme Function Lysyl oxidase Indole 2,3-dioxygenase Dopamine monooxygenase Superoxide dismutase 1 izoenzyme Ceruloplasmin Collagen and elastin cross-link Tryptophan metabolism Norepinephrine synthesis Antioxidant Ferroxidase activity, chaperone binding, copper and iron transports Ferroxidase activity Melanin synthesis Oxidation of monoamine and diamines, detoxication of serotonin, spermidine, putresin,1 phenyl-ethylamine ATP production Hephestin Tyrosinase Amine oxidase Cytochrome c oxidase • Copper is absorbed mainly in the small intestine and slightly in stomach. • The intestinal uptake is dependent on pH. • Approximately, 40%-70% of ingested copper is absorbed • If copper content is low(lower than 1 mg/day), the absorption is around 50% whereas, if it is high around(higher than 5mg/day) 20% is absorbed *ceruloplasmin • It is synthesized in the liver. • It is an acute phase reactant. • It has ferroxidase activity. • It has antioxidant properties. • It contains 6-8 copper • Ceruloplasmin enables iron to be oxidized (Fe+3) with its ferroxidase activity and provide to bind transferrin • Normal value of serum copper level in a healthy adult is 65-165 g/dL Higher-than-normal serum copper level hypercupremia • Lower than normal serum copper level, hypocupremia *Disorders of copper metabolism • Menkes’ disease • Menkes disease (Menkes kinky hair syndrome), a progressive neurodegenerative disease with X-linked recessive inheritance starting from early childhood • Due to the mutation in the gene of the Cu+2 -carrying ATPase, the transport and storage of copper is impaired. • Low levels of plasma copper • The most important findings to support the diagnosis are hair findings. Lightening in hair color, wooly, hard and mixed hair is typical. • (Due to the loss of disulfide bond catalyzed by Cu+2------ Lysyl oxidase) If untreated, death occurs due to dysfunction of copper enzymes. *Wilson’s disease •It is a genetically determined copper accumulation disease. •. Loss- of- function mutation of gene that encodes ATP7B is lead to Wilson’s disease •Neurological disorders, liver cirrhosis, Kayser- Fleischer ring (green-brown discoloration) due to copper deposition •Copper accumulation in all tissues, especially liver, brain (Basal ganglia), cornea and kidneys Symptoms and signs Wilson cirrhosis • Serum ceruloplasmin levels are low. • Total serum copper decreased due to ceruloplasmin deficiency, but serum free copper increased. • Quantitative copper increase in liver biopsy (Gold standard in diagnosis) Copper toxicity • It can be formed by copper pots, some burn pomades and fungicides. • Bleeding in the GIS, renal dysfunction, and neurological findings are in question. manganese • Almond, apricot, bran, kidney, lentil, parsley, walnut, cress, wheat extract are manganese rich nutrients • It is absorbed through the small intestine by a mechanism similar to iron absorption. • It is found in many metalloenzyme structures in the form of Mn+2, Mn+3. • Enzymes containing Mn in their structure -arginase -Pyruvate carboxylase -Superoxide dismutase; -Transferase, - decarboxylase, -hydrolases; • Bone development; It is a cofactor of glycosyltransferase, which enables the synthesis of proteoglycans. • wound healing; in collagen and glycosaminoglycan synthesis Neuromuscular disorders and schizophrenia-like findings in manganese intoxication • Excess manganese activates atherosclerosis. • Manganese Deficiency: Irregularity in balance, infertility, decreased desire for sex, abnormal development in the body,increase birth of a dead child Chromium (Cr) • Cr +3 and Cr +6 valence forms are found in biological systems. • glucose tolerance factor • It strengthens the effects of insulin. • Facilitates the binding of insulin to its receptors • Insulin is ineffective as a glucose regulator without chromium. Chromium deficiency leads to atherosclerosis