NT-7 Copper and Zinc 2024-2025 University of Baghdad PDF

University of Baghdad College of Medicine 2024-2025 Title: Minerals (Zinc & Copper) Grade: third Module: Nutrition, Water & Electrolytes Imbalances (NT) Speaker: Assist. Prof. Dr. Thikra Hasan Mathkor Date: 22/10/2024 Objectives: - To analyze the dis...

University of Baghdad College of Medicine 2024-2025 Title: Minerals (Zinc & Copper) Grade: third Module: Nutrition, Water & Electrolytes Imbalances (NT) Speaker: Assist. Prof. Dr. Thikra Hasan Mathkor Date: 22/10/2024 Objectives: - To analyze the distribution, absorption mechanisms, biological functions, and potential deficiency and toxicity levels of zinc in the human body, highlighting its essential roles in enzymatic processes and immune function. - To examine the distribution, absorption pathways, biological significance, and associated deficiency and toxicity risks of copper, emphasizing its critical contributions to metabolic processes and neurological health.  Distribution of zinc in human body Zinc is mainly intracellular element. RDA of Zinc in adults= 10-15 mg/day Zinc absorption Zn absorption is facilitated by a low molecular weight Zinc binding factor produced and secreted by Pancreas (zinc importer (ZiP) and transporter (ZnT) families Zn absorption is interfered with High amounts of dietary Ca, P and Phytates. Blood Zinc Levels 120- 140 μg/100ml Zinc is associated with Albumin in blood. Functions of zinc in human body The broad spread of zinc through the body at the organ, cellular and even protein levels suggests that the function of most systems is dependent on zinc. Enzyme Function RNA polymerase Transcription, synthesis of mRNA Carboxypeptidase A Protein digestion in intestine Protein kinase C Signal transduction Respiration/buffering/hydration of Carbonic anhydrase CO2 Cytochrome c oxidase Respiration/electron transport chain Alcohol dehydrogenase Ethanol metabolism Superoxide dismutase Inactivation of free radicals Nitric oxide synthase Signaling, vasodilation Blood pressure regulation/activation Angiotensin converting enzyme of angiotensinogen Zinc Transcription Factors  Zinc Transcription Factors -There are many zinc enzymes but even more transcription factors utilize zinc. Variable numbers of zinc atoms are each coordinated by four cysteine or histidine residues to stabilize a DNA binding structure (characteristic zinc finger domains). -An important class of zinc finger transcription factors is the steroid/thyroid receptor superfamily, responsible for mediating the biological response to a wide range of hormonal and metabolic signals, including retinoic acid and vitamin D. Metallothioneins Metallothioneins (MTs) are a family of proteins that play a vital role in metal ion homeostasis and detoxification They are rich in sulfhydryl groups and can be found in various tissues, including the liver, kidney, and intestine. When MTs bind to physiological heavy metals, such as cadmium, mercury, zinc and copper, they can participate in regulating cell growth and proliferation and protecting the body against oxidative stress MT may trap zinc within the epithelial cells, causing it to be lost to feces as the cells are sloughed off. This may be part of the explanation of how zinc absorption is adjusted to meet needs. Acrodermatitis enteropathica - Congenital malabsorption of zinc -is an autosomal recessive condition of zinc malabsorption, which can lead to severe deficiency. -Gene mutations that lead to this condition have been identified in ZIP4, which encodes one of the zinc transporters. -This protein has been localized to the apical membrane of intestinal epithelial cells Copper absorption -Copper-transporting ATPases play critical roles in intestinal absorption (ATPase copper-transporting alpha; ATP7A) and biliary excretion (ATPase copper- transporting beta; ATP7B), -and their dysfunctionality underlies Menkes disease (MD) and Wilson’s disease (WD). -After absorption, most dietary copper enters the liver where it may be: stored in metallothionein, incorporated into ceruloplasmin (CP) or distributed in the blood to various organs. -Circulating CP participates in iron metabolism, while atomic cupric (Cu2þ) copper bound to various serum ligands functions as transport copper. Role of copper in iron metabolism Transport of Iron Storage of Iron Utilization of Iron Heme Biosynthesis  Deficiency Of Copper Deficiency of Copper consequently lowers: * Saturation of Transferrin/Ferritin Levels * Hb concentration/Oxygen supply to tissues * ATP production in body Deficiency of Copper in body directly and indirectly affects: Iron Metabolism Heme Biosynthesis (weakness, weight loss) Leads to Iron deficiency Anemia Melanin Biosynthesis (Demyelination) Collagen Biosynthesis (bone disorder) Menkes Disease Kinky /Steel Hair Syndrome A Copper Deficiency Disorder It is inherited X linked disorder affects male only. Defects in intestinal Copper absorption. Due to absence of Copper binding ATPase Defective Transport of Copper across the Serosa of mucosal cell membrane. Clinical Manifestations Of Cu Deficiency Iron Deficiency Anemia Depigmentation of hair Mental Retardation Abnormal Bone formation Susceptible to Infections. Copper Toxicity Disorder Wilsons Disease (Hepatolenticular Degeneration) Wilsons Disease is inherited as Autosomal Recessive. Incidence of Wilsons Disease is 1 in 50,000 of live births. Biochemical Defect the copper is loaded onto apoceruloplasmin or exocytosed into bile by a metal ptype atpa that is coded by the atp7b gene found on chromosome 13 In Wilson's disease mutations in the atp7b gene lead to a lack of this protein or its activity leading to an inability to form ceruloplasmin and an inability to excrete copper in the bile eading to Copper accumulation Copper is not excreted through bile. In Wilson disease, the Copper builds up in toxic levels in Liver, In Wisons disease due to low Ferroxidase activity of Ceruloplasmin The Iron transport and Storage is indirectly affected. it deposits in the basal ganglia it can cause a movement disorder it can deposit membrane of the cornea which is this membrane between the stroma and the endothelial layer of the cornea so you look for something called kaiser fletcher rings Summary Zinc is primarily an intracellular element essential for various biological functions, with a recommended dietary allowance (RDA) of 10-15 mg/day for adults. Its absorption is facilitated by zinc-binding factors produced by the pancreas and zinc is often associated with albumin in circulation. high levels of dietary calcium, phosphorus, and phytates can hinder this zinc absorption. Zinc plays a critical role in numerous enzymatic reactions and is integral to the function of zinc finger transcription factors, particularly in hormonal signaling. Metallothioneins (MTs) are key proteins involved in metal ion homeostasis and detoxification, regulating cell growth and protecting against oxidative stress. Acrodermatitis enteropathica, a genetic disorder caused by mutations in the ZIP4 gene, leads to severe zinc malabsorption, highlighting the importance of zinc transport mechanisms in health. Summary Copper is a vital trace element essential for numerous physiological functions. Approximately 10% of dietary copper is absorbed in the duodenum, facilitated by copper-transporting ATPases (ATP7A and ATP7B), whose dysfunction can lead to Menkes disease (MD) and Wilson’s disease (WD). Post-absorption, copper is primarily stored in the liver, incorporated into ceruloplasmin, or distributed to various organs, playing a crucial role in iron metabolism. Copper is a key component of several enzymes, including cytochrome oxidase and superoxide dismutase, and is involved in collagen synthesis. Copper deficiency can lead to anemia, impaired iron metabolism, and bone disorders, while excess copper accumulation in Wilson’s disease results in neurological and hepatic complications. Treatment for Wilson’s disease includes chelation therapy with penicillamine to remove excess copper from the body.  ‫ئ‬ ‫ل‬ ‫شكرا حسن اصغا مك‬