Nutrition Module: Zinc & Copper Overview

University of Baghdad, College of Medicine, 2024-2025

• Location: Baghdad, Iraq
• Academic year: 2024-2025
• Course title: Minerals (Zinc & Copper)
• Grade level: Third
• Module title: Nutrition, Water & Electrolytes Imbalances (NT)
• Lecturer: Dr. Thikra Hasan Mathkor
• Date of lecture: 22/10/2024

Objectives

• Analyze zinc distribution, absorption mechanisms, biological functions, potential deficiency/toxicity levels, and roles in enzymatic/immune function.
• Examine copper distribution, absorption pathways, biological significance, associated deficiency/toxicity risks, and contributions to metabolic/neurological health.

Zinc in Human Body

• Primarily an intracellular element.
• Recommended daily allowance (RDA) for adults: 10-15 mg/day
• Distribution: skeletal muscle (60%), bone (30%), skin (5%), other tissues (brain, kidney, pancreas, heart) (5%), plasma (~0.1%).

Zinc Absorption

• Facilitated by low molecular weight zinc-binding factors produced by the pancreas (zinc importers/transporters, ZIPs and ZnTs).
• Interfered with high amounts of dietary calcium, phosphorus, and phytates.
• Blood zinc levels: 120-140 µg/100ml
• Associated with albumin in blood.
• Losses occur through faeces, sweat, urine, seminal fluid.

Zinc Functions

• Broadly spread throughout the body, influencing organ, cellular, and protein function.
• Essential for many systems, including immunity (T&B cells, antibody production), metabolism (insulin storage/secretion, receptor function), other sensory function (night vision, taste, olfaction), cardiovascular health (blood pressure, mucociliary clearance).

Zinc Enzymes

• RNA polymerase: Transcription, synthesis of mRNA
• Carboxypeptidase A: Protein digestion in intestine
• Protein kinase C: Signal transduction
• Carbonic anhydrase: Respiration (buffering/hydration of CO2)
• Cytochrome c oxidase: Respiration/electron transport chain
• Alcohol dehydrogenase: Ethanol metabolism
• Superoxide dismutase: Inactivation of free radicals
• Nitric oxide synthase: Signaling, vasodilation
• Angiotensin converting enzyme: Blood pressure regulation

Zinc Transcription Factors

• Many zinc enzymes and transcription factors utilize zinc atoms coordinated by cysteine/histidine residues to stabilize DNA-binding.
• Some factors are important in the biological response to various signals, such as hormones.

Metallothioneins (MTs)

• A family of proteins involved in metal ion homeostasis and detoxification, rich in sulfhydryl groups.
• Found in liver, kidney, and intestine.
• Bind to physiological heavy metals (cadmium, mercury, zinc, and copper) to regulate cell growth, proliferation, and offer antioxidant protection.
• Can trap zinc, leading to loss in feces as epithelial cells shed.

Enteric Zinc and Copper Absorption

• Normal absorption involves metallothionein activity.
• Excess zinc increases metallothionein production, binding copper and transporting it back to the gut for excretion.

Acrodermatitis Enteropathica

• Congenital malabsorption of zinc.
• Autosomal recessive disorder
• Causes severe zinc deficiency.
• Defects in the zinc transporter gene (ZIP4) localized to the apical membrane of intestinal epithelial cells.
• Manifestations: skin inflammation, around orifices, tips of fingers and toes, diarrhea, hair loss, growth retardation, anorexia, and crying.

Copper Absorption

• Copper-transporting ATPases (ATP7A and ATP7B) are critical in intestinal absorption and biliary excretion.
• Dysfunction of ATP7A and ATP7B underlies Menkes and Wilson's disease.
• Copper can be stored in metallothionein or incorporated into ceruloplasmins in the liver.
• Circulating ceruloplasmin plays a role in iron metabolism and transport.

Copper’s role in enzymes

• Cytochrome oxidase
• Phenol oxidase/uricase
• ALA synthase
• Ascorbic acid oxidase
• Catalase
• Tyrosinase
• Superoxide dismutase
• Monoamine oxidase

Copper Function & Role in Hemoglobin

• Essential for hemoglobin synthesis.
• Needed for ALA synthase, a molecule used in heme synthesis.
• Essential in elastin and collagen synthesis.

Copper and L-Tyrosine in Melanin Synthesis

• Tyrosinase activity, with copper in the active center, catalyzes L-Tyrosine's conversion to L-Dopaquinone, an important step in melanin synthesis.

Copper Role in Iron Metabolism

• Ceruloplasmin, a copper-dependent oxidase, plays a role in oxidizing ferrous iron (Fe2+) to ferric iron (Fe3+).
• Crucial for iron transport in the blood via transferrin.

Copper-containing non-enzymatic proteins

• Hepatocuprein
• Hemocuprein
• Cerebrocuprein

Copper Deficiency

• Reduced transferrin/ferritin saturation.
• Lower Hb concentration/oxygen supply to tissues.
• Decreased ATP production.
• Directly/indirectly affects iron metabolism, heme biosynthesis (weakness, weight loss), iron deficiency anemia, melanin/collagen biosynthesis (demyelination/bone disorder).

Menkes Disease

• Inherited X-linked disorder affecting only males.
• Defect in copper absorption in the intestine.
• Defective transport of copper across the serosal membrane.
• Clinical manifestations: kinky hair, mental retardation, abnormal bone formation, susceptible to infections.

Wilson's Disease

• Autosomal recessive disorder.
• Increased copper absorption.
• Reduced/defective copper excretion in bile.
• Accumulation of copper in the liver, brain/nervous system and other tissues.
• Clinical manifestations: Hepatic cirrhosis, brain necrosis, neurological problems, Kayser-Fleischer rings(rings in the cornea).

Copper Toxicity Treatment

• Penicillamine (DP): Used to excrete copper through the urine and is a preferred standard of therapy for Wilson's disease.
• Treatment involves chelation therapy for excessive copper accumulation by sequestering the metal, rendering it nontoxic.

This quiz covers the essential aspects of zinc and copper in human nutrition, focusing on their distribution, absorption mechanisms, and biological functions. It aims to analyze potential deficiencies and toxicities associated with these minerals, which are crucial for enzymatic and immune functions. Suitable for third-year medical students in the College of Medicine.