Week 7

Trace elements  Micro-nutrients are chemical elements required in minute amounts  Usually as part of a vital element.  There are 19 trace elements divided into three groups (WHO classification):  Essential elements

They are : 1. zinc (Zn), 2. copper (Cu) 3. selenium (Se) 4. chromium (Cr) 5. cobalt (Co) 6. Manganese (Mn) 7. molybdenum (Mo).

3rd most important trace element  Copper combines with certain proteins to produce enzymes that act as catalysts to help several body functions.  Some help provide energy required by biochemical reactions.  Others are involved in the transformation of melanin for pigmentation of the skin and still others help to form cross- links in collagen and elastin and thereby maintain and repair connective tissues.  This is especially important for the heart and arteries.

 Copper is carried mostly in the bloodstream on a plasma protein ( a blood protein ) called ceruloplasmin.  When copper is first absorbed in the gut it is transported to the liver bound to albumin.  Copper is found in a variety of enzymes, including the copper centers of cytochrome c oxidase and the enzyme superoxide dismutase (containing copper and zinc).  In addition to its enzymatic roles, copper is used for biological electron transport.

Copper forms two series of compounds:  copper (I/cuprous)  copper (II/cupric) compounds.

 Is component of a cofactor for approximately 50 different enzymes. These enzymes need copper to function properly.  Is essential for iron absorption and transport.  Iron is needed to make haemoglobin, a main component of red blood cells. Therefore, copper deficiency is often linked to iron-deficiency anemia.  Is required to build elastin and collagen, which are an important component of bones and connective tissues. Therefore, copper is believed to protect the bones and joints against degeneration and osteoporosis.  Is required for melanin (pigment) production. People with copper deficiency may have pale skin and hair.  Is a key mineral for the immune system. Copper promotes wound healing.

Haemoglobin is the iron-containing oxygen- transport metalloprotein in the red blood cells of the blood.

Elastin, is a protein in connective tissue that is elastic and allows many tissues in the body to resume their shape after stretching or contracting.

Collagen is the most abundant protein in mammals

copper deficiency produces an extensive range of symptoms. These symptoms include: - iron deficiency anemia - osteoporosis - ruptured blood vessels - neutropenia - joint problems (arthritis) - brain disturbances - elevated LDL cholesterol and reduced HDL cholesterol levels - increased susceptibility to infections due to poor immunity - loss of pigment in the hair and skin (Menkes’ Syndrome) - poor thyroid function - irregular heartbeat - intolerability of glucose

 Copper works with vitamin C to help make a component of connective tissue, elastin.  Osteoporosis is defined as a disease in the bone in which the bone mineral density is reduced, bone microarchitecture is disrupted, and the amount and variety of non-collagenous proteins in the bone is altered. Osteoporotic bones are more at risk of fracture.

Neutropenia is a hematological (study of blood) disorder characterized by an abnormally low number of neutrophil granulocytes (a type of white blood cell and serves as the primary defense against infections by destroying bacteria in the blood).

Arthritis is inflammation of the joints. Copper’s anti-inflammatory actions may help in reducing arthritis symptoms.

Menkes disease (also called the kinky hair disease or Menke’s kinky hair syndrome) is a disorder that affects copper levels in the body.  It is characterized by sparse and coarse hair, growth failure, and deterioration of the nervous system. Onset of Menkes syndrome typically begins during infancy.  Signs and symptoms of this disorder include weak muscle tone (hypotonia), sagging facial features, seizures, mental retardation, and developmental delay.  The patients have brittle hair and metaphyseal widening. In rare cases, symptoms begin later in childhood and are less severe. It is a X-linked recessive disorder, therefore males have the disease, while females are carriers.

Copper in excess amounts is usually caused by over supplementation. Excessive intake of copper can cause: - abdominal pain and cramps - diarrhea - liver damage The toxic effects of high tissue levels of copper are seen in patients with Wilson’s disease  A genetic disorder characterized by copper accumulation in various organs due to the inadequate synthesis of ceruloplasmin (the protein that transports copper through the blood) by the liver.  Wilson’s disease primarily effects the liver, kidneys, and brain causing degenerative physiological changes (including cirrhosis of the liver, muscular rigidity and spastic contraction, and emotional disturbances) that are fatal if untreated.  The treatment of Wilson’s disease involves avoidance of foods rich in copper and any supplements containing copper and drug treatment with chelating agents that remove the excess copper from the body.

Second most abundant trace element  Cofactor – DNA polymerase, alkaline phosphatase, carboxypeptidase  Regulate- growth, immune system, collagen synthesis, wound healing, bone metabolism, reproduction, taste, smell & vision

 Skin lesions (acrodermatitis)  Growth retardation  Anorexia  Poor wound healing  Decreased night vision  Hypogonadism  Impaired immune function  Diarrhea  Depressed mental function  Teratogenesis

 70% bound to albumin in serum  Absorbed mainly in small bowel

Play a central role in the immune system and Zn deficient individuals experience increased susceptibility to a variety of pathogens. Affects multiple aspects of the immune system from the barrier of the skin to gene regulation within lymphocytes.  Zn is crucial for normal development and function of cells mediating non- specific immunity such as neutrophils and natural killer cells.  Zn deficiency also affects development of acquired immunity by preventing both the outgrowth and certain functions of T cells such as activation, Th1 cytokine production, and B cell help.  The macrophage, a pivotal cell in many immunological functions, is adversely affected by Zn deficiency, which can dysregulate intracellular killing, cytokine production, and phagocytosis.  Zn deficiency affects the development of acquired immunity by regulating growth and function of T and B cells. Zn is needed for DNA replication, RNA transcription, cell division, and cell activation.  Apoptosis is potentiated by Zn deficiency and Zn also functions as an antioxidant and can stabilize membranes.

 Component of several enzymes; requires bile for absorption  Deficiency: weight loss, transient dermatitis, n/v; changes in color, and slow growth of hair; sterility

 Miners  Accumulates in liver  Accumulates in CNS  Parkinson-like symptoms

 No deficiency has been described in humans or other animals

 Inorganic lead compounds have been known to be a toxic hazard

 Clear proof of the essentiality of chromium in humans has been difficult to attain