Functions of Iron 1. Iron serves as a ____ with cytochrome oxidase, xanthine oxidase, peroxidase, and catalase 2. It is transported by the 2 transport proteins known as ____ and ____ 3. It comes in 2 forms: ____ (Fe3+) and ____ (Fe2+)

1. Cofactor 2. Transferrin and albumin 3. Ferric (3) and Ferrous (2)

1. In what parts (2) of the intestine is iron absorbed? 2. Between the ferric and ferrous form, what form exists in our diet and what form does it convert into for it to be absorbed?

1. Duodenum and Jejunum 2. Ferric (diet) to Ferrous (inside our body)

(P) Lec 3: Trace Elements (Part 1) Flashcards by Kchianna Lauren Coronel

Trace elements are found in the body in very ____ concentrations

Little

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Trace elements are known to constitute less than ____% of the total body weight

0.01%

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Indicate their percentages when in the body:
- Water
- Electrolytes
- Trace Elements

Water: 96%
Electrolytes: 3.98%
Trace Elements: The remaining

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Classification of Trace Elements

What type of trace element?
- If the replacement of the deficient element corrects an impairment
- It cannot be synthesized by the body in large amounts hence it should be present in the diet

Essential

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Classification of Trace Elements

A deficiency of these elements may be due to the ff. EXCEPT:
A. Decreased intake
B. Increased secretion and excretion
C. Excessive cellular stress
D. Impaired absorption
E. Genetic abnormalities

C. Excessive cellular stress

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Classification of Trace Elements

Excess concentrations are associated with at least some degree of toxicity leading to what?

Intoxication

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Classification of Trace Elements

Essential trace elements are often associated with 1.) what enzymes and 2.) what proteins as cofactors?

Metalloenzymes
Metalloproteins

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Classification of Trace Elements

Includes: Copper (Cu), Chromium (Cr), Cobalt (Co), Iron (Fe), Manganese (Mn), Molybdenum (Mo), Zinc (Zn), Selenium (Se), Iodine (I), and Fluorine (F)

Essential

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Classification of Trace Elements

What type of trace element?
- Any element that is not considered as the other type
- These are of medical interest primarily because many of them are toxic in the body

Non-Essential

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Biological Functions of Trace Elements

Fill in the blanks
1. ____ transport
2. Respiration
3. ____ activities
4. ____ activator or cofactor
5. Protection from ____
6. Tissue repair
7. Immune system
8. Growth and reproductive process

Electron
Hormonal
Enzyme
Free radicals

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Biological Functions of Trace Elements

Which among coenzymes and cofactors are organic and inorganic?

Organic = Coenzymes
Inorganic = Cofactors

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Biological Functions of Trace Elements

This is an enzyme composed of zinc and copper which has an antioxidant effect and are known to be scavengers of free radicals

Superoxide Dismutase (SOD)

Note: Superoxide by itself is a free radical

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Biological Functions of Trace Elements

Whenever a free radical is present in the body, such as a superoxide (2(O2)), the Superoxide Dismutase will produce what 2 products?

Oxygen (O2) and Hydrogen Peroxide (H2O2)

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Biological Functions of Trace Elements

Upon the production of water and peroxide using the Superoxide Dismutase (SOD), it will be acted upon by what 2 possible enzymes to convert them into water (H2O) and oxygen (O2)?

Catalase
Peroxidase

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Biological Functions of Trace Elements

(2(O2)) [superoxide] + SOD [superoxide dismutase] = ?

Oxygen (O2)
Hydrogen Peroxide (H2O2)

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Biological Functions of Trace Elements

H2O2 [hydrogen peroxide] + catalase/peroxidase = ?

Water (H2O) and Oxygen (O2)

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Biological Functions of Trace Elements

This is a known component of glutathione that regenerates Vitamin B & C important for free-radical protection

Selenium

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Biological Functions of Trace Elements

This is an active agent of wound healers and its component facilitates wound healing

Active agent: Zinc sulfate
Facilitator of wound healing: Zinc

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The most abundant trace element in the body
A known constituent of Hgb and myoglobin as it is able to carry oxygen
An agent in redox reactions and electron transport
Only excreted during menstruation through the sloughing off of the epithelium

Iron

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Functions of Iron

Iron serves as a ____ with cytochrome oxidase, xanthine oxidase, peroxidase, and catalase
It is transported by the 2 transport proteins known as ____ and ____
It comes in 2 forms: ____ (Fe3+) and ____ (Fe2+)

Cofactor
Transferrin and albumin
Ferric (3) and Ferrous (2)

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Accumulation of free iron in plasma is toxic, so therefore an excess of it should be stored in the form of ____ or ____

Ferritin or Hemosiderin

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In what parts (2) of the intestine is iron absorbed?
Between the ferric and ferrous form, what form exists in our diet and what form does it convert into for it to be absorbed?

Duodenum and Jejunum
Ferric (diet) to Ferrous (inside our body)

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In order for Ferric iron to be converted into Ferrous iron, what (4) components must it interact with?

HCl (from the stomach)
Organic acids
Vitamin C
Ferric reductases (responsible for conversion)

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Once the iron is in ferrous form, it will be absorbed in the duodenum and jejunum where it will later on complex with what (2) transport proteins?

Transferrin and Albumin

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Transferrin and albumin are able to deliver iron to different parts of the body such as the BM, liver, and spleen where it will be stored in the form of what? (2)

Ferritin and Hemosiderin

- This is composed of 4,500 atoms of iron - Is formed when iron combines with apoferritin produced by the organs that store iron (BM, spleen, and liver)

Ferritin

If apoferritin is not present due to inflammation or infection, iron cannot bind with it to be stored as ferritin, therefore it will be stored as?

Hemosiderin

- This is stained using a Prussian Blue/Pearl stain - It is seen as small oxide granules producing blue to black granules - Aka the EXTRACELLULAR form of iron however it is NOT THE PRIMARY storage form

Hemosiderin | Note: This is only the storage form if apoferritin is not present

In cases of overstimulation of macrophages wherein there is an increased amount of apoferritin, an increased amount of iron will combine with apoferritin which does what to the circulating iron in the blood?

Decreases

Refers to: - Excess iron in plasma - Toxicity as it can result to low oxidation of cells that can lead to DNA destruction

Iron Overload

# Causes of Iron Overload 1. Refers to when RBCs lyse which releases the Hgb that contains iron 2. When there is increased ceruloplasmin in blood (protein that transports copper) 3. A reduction or failure of iron to be incorporated to form heme or a protoporphyrin ring (e.g. lead poisoning, thalassemia, and Vit. B16 deficiency) 4. When iron cannot be absorbed by the small intestine (e.g. pernicious anemia) 5. During cases of hemosiderosis and repeated transfusions resulting to an increased RBC load

1. Hemolytic anemia (increased RBC destruction) 2. Increased mobilization of iron 3. Decreased blood cell formation 4. Defective iron storage 5. Increased rate of absorption

# Causes of Iron Overload - This is a protein responsible for the transport of copper which is known to facilitate iron mobilization from ferritin to transferrin - An increase of this protein means increased iron mobilization and is present in cases of hepatic cirrhosis

Ceruloplasmin

Iron overload is collectively referred to as ____ ____ which can result to the malfunctioning of the organs where iron accumulates (endocrine glands, liver, and heart)

Hereditary Hemochromatosis

# Causes of Iron Deficiency 1. An example of this is iron-deficiency anemia (IDA) 2. Happens in cases of hemorrhage 3. During an impairment with the mobilization of iron due to decreased ceruloplasmin

1. Generalized iron deficiency 2. Chronic loss 3. Impaired release of iron from the RES

# Laboratory Evaluation of Iron - Non-hemolyzed serum is needed (a hemolyzed sample could result to a false positive) - An early morning sample (12hr fasting) is also needed due to the diurnal variation of iron - This measures the free iron (bound with transferrin and albumin but not with apoferritin) in the blood

Serum Iron

# Laboratory Evaluation of Iron Iron is theoretically expected to be increased in the ____ and decreased in the ____

1. Increased: Morning 2. Decreased: Afternoon

# Laboratory Evaluation of Iron A form of iron that refers to those that are bound with transferrin and albumin but not bound to apoferritin

Free Iron

# Laboratory Evaluation of Iron Give the normal values of serum iron for males and females

1. Males = 65-117 ug/dL or 11.6-31.7 umol/L 2. Females = 50-170 ug/dL or 9.0-30.4 umol/L

# Measuring Serum Iron Levels 1. When measuring iron, it should be separated from binding proteins, through the use of a ____ 2. When separating, you cannot use ____ 3. Once separated, ferric iron will now be reduced to ferrous iron through the use of reducing agents such as ____ 4. Once reduced, the ferrous iron is now complexed with ____ such as ferrene, terosite, 2, 4, 6-tripyridyl-S-triazine (TPTZ), and sulfonated bathophenanthroline (SBP) 5. The end product/color is measured via ____

1. Strong acid 2. Trichloroacetic acid (TCA) 3. Ascorbic acid (or any acid substance) 4. Chromogens 5. Spectrophotometry

# Laboratory Evaluation of Iron - A test considered as an indirect measure of serum transferrin or free transferrin - The amount of iron that could be found by saturating the binding proteins (transferrin) present in the sample - Can differentiate iron-deficiency anemia (IDA) from anemia of chronic disease (ACD) - Normal values range from 240-250 ug/dL or 43-80.6 umol/L

Total Iron Binding Capacity (TIBC)

# Total Iron Binding Capacity (TIBC) Increased or Decreased TIBC? 1. Iron Deficiency Anemia (IDA) 2. Anemia of Chronic Disease (ACD)

1. IDA - increased 2. ACD - decreased

# Total Iron Binding Capacity (TIBC) This condition leads to low iron circulation due to the overstimulation of macrophages. This stimulation results in the production of apoferritin, to which iron binds, consequently increasing ferritin.

Anemia of Chronic Disease (ACD)

# Laboratory Evaluation of Iron - Aka transferrin saturation - Measures the percent (%) transferrin bound with iron - Can also be used to differentiate Iron-Deficiency Anemia (IDA) and Anemia of Chronic Disease (ACD) - Normal values range from 20-55%

Percent Saturation

# Percent Saturation Increased or Decreased Percent Saturation? 1. Anemia of Chronic Disease (ACD) with decreased TIBC 2. Iron-Deficiency Anemia (IDA) with increased TIBC

1. ACD - increased 2. IDA - decreased

# Serum Transferrin Increased or Decreased Serum Transferrin? 1. Iron-Deficiency Anemia (IDA) 2. Anemia of Chronic Disease (ACD)

1. IDA - increased 2. ACD - decreased

# Laboratory Evaluation of Iron - A direct measurement of free transferrin - Is measured in the lab using a nephelometry assay - An index of iron nutritional status - Can also be used to differentiate Iron-Deficiency Anemia (IDA) and Anemia of Chronic Disease (ACD) - Normal values range from 200-400 mg/dL

Serum Transferrin

# Laboratory Evaluation of Iron - Is measured using ELISA or Chemiluminescence - An index of iron stores - Can also be used to differentiate Iron-Deficiency Anemia (IDA) and Anemia of Chronic Disease (ACD)

Serum Ferritin

# Serum Ferritin Increased or Decreased Serum Ferritin? 1. Anemia of Chronic Disease (ACD) 2. Iron-Deficiency Anemia (IDA)

1. ACD - increased 2. IDA - decreased

- The second most abundant element in the body - A component of more than 300 enzymes - It promotes a healthy immune system, it promotes wound healing, ovulation, sperm development, DNA synthesis, and growth development - It synthesizes the metabolism of proteins, glucose, and cholesterol

Zinc

1. The absorption of zinc is through ____, which is similar to how copper is absorbed 2. These (2) serve as transport proteins of zinc 3. Zinc is ____ proportional to copper

1. Metallothionine 2. Albumin and A2-Macroglobulin 3. Inversely

- An intoxication of this is rare as the more one has of this element, the better - Exposure to its oxide fumes and dust may cause "Fume Fever" with chemically-induced symptoms such as pneumonia, severe pulmonary inflammation, fever, hyperpnea, coughing, pains in legs and chest, and vomiting

Zinc Excess

- This causes dwarfism, delayed sexual maturation, hypovoletism, and testicular atrophy - There is prolonged wound healing causing Acrodermatitis enterophatica

Zinc Deficiency

- This is an inherited condition wherein there is a zinc malabsorption that results in a decreased zinc level in the body. - It is characterized by dermatitis, hyperpigmented lesions, alopecia, growth retardation, infection, facial rash, and diaper rash - Is common in infants and presents with prolonged wound healing

Acrodermatitis enterophatica (zinc deficiency)

- A trace element with excellent electrical and heat conducting properties - Assumes 4 different states: (0, +1, +2, +3) - An important cofactor for several metalloenzymes and is critical for the reduction of iron during heme synthesis

Copper

Among the 4 different states of copper: 1. Which is the most stable? 2. Which is present in the diet? 3. Which can be absorbed by the intestine?

1. Cu(+2) 2. Cu (+1) 3. Cu (2+) | Note: Cu+1 is oxidized into Cu+2

- This is formed when your copper molecule is combined with apoceruloplasmin - This is the form that can be distributed all throughout the body as 90% of it in the body is in this form

Ceruloplasmin

Its metalloenzymes include: ceruloplasmin, cytochrome C oxidase, SOD, tyrosinase, lysyl oxidase, dopamine hydroxylase, clotting factor V, metallothionine, and an unknown enzyme cross-linking keratin in hair

Copper

- This is a constituent of erythrocuprein found inside the RBCs with antioxidant activity together with superoxide dismutase - Is absorbed in both the intestines and stomach - Its transport proteins include: transcuprein, albumin, ceruloplasmin, and low molecular weight components in the portal system

Copper

# Fates of Copper 1. Upon entering the liver, copper complexes with apoceruloplasmin producing ____ 2. It will then go through the bile canaliculus and mix together with the bile, making it the biliary ____ of copper 3. Copper chaperones can bind with thionine producing ____, a non-toxic storage form of copper

1. Ceruloplasmin 2. Excretion 3. Metallothionein

Metallothionein could be excreted in the ____ or stored as Metallothionein before entering the circulation as ____

1. Bile 2. Ceruloplasmin

# Copper's Biological Functions 1. A cofactor of the superoxide dismustase metalloenzyme 2. A cofactor for lysyl oxidase (an enzyme that cross-links proteins into fiber) 3. A cofactor for tyrosinase 4. A cofactor for norepinephrine and B-dopamine monooxygenase 5. A cofactor for metallothionein

1. Antioxidant defense 2. Collagen formation 3. Melanin production 4. Production of neurotransmitters 5. Metallothionein

# Match the enzyme with the function (Copper) 1. Antioxidant Defense 2. Collagen Formation 3. Melanin Production 4. Production of Neurotransmitters 5. Metallothionein A. Tyrosinase B. Norepinephrine and B-dopamine monooxygenase C. Copper chaperones bound to thionine D. Superoxide dismutase E. Lysyl oxidase

1. D 2. E 3. A 4. B 5. C

Copper can be excreted through what 4 body fluids?

1. Bile (98% excretion) 2. Urine 3. Sweat 4. Menstruation (small amount)

What disease falls under copper overload disorders?

Wilson's Disease

What 2 diseases fall under copper deficiency disorders?

1. Menke's Kinky Hair Syndrome 2. Increased Zinc Absorption

- Aka hepatolenticular degeneration; a decrease in ceruloplasmin which increases the copper in blood - It also presents with an increase in urinary excretion of copper in response to an increased amount - Increased metallothionein is also a manifestation - Can be treated with D-penicillamine, Dimercaprol, and Ammonium tetramolybdate - Affects the CNS, liver, kidneys, heart, bones, and eyes

Wilson's Disease (Copper Excess)

This refers to the presence of a brown pigment deposit in the cornea of the eye due to increased copper Identify the diagnostic symptom and which disease does it correspond to

Kayser-Fleischer Ring (Wilson's Disease)

# Zinc Excess D-penicillamine, Dimercaprol, and Ammonium tetramolybdate as treatments: 1. Promotes the ____ excretion of copper 2. Ammonium tetramolybdate ____ copper absorption in the stomach and small intestine

1. Urinary 2. Inhibits

- A sex-linked connective tissue defect involving copper transport (extreme form of deficiency) - Manifested by steely and peculiar hair and mental retardation

Menke's Kinky Hair Syndrome (copper deficiency)

- Increased zinc supplement results in decreased absorption of this element - Zinc can be used to treat Wilson's disease - May result in connective tissue defects, hypotonia or decreased muscle tone, Menke’s kinky hair, and kidney, liver, and CNS defects - Symptoms include hypothermia, mental deterioration, and seizures due to a decreased copper level

Increased Zinc Absorption (copper deficiency)

- This potentiates insulin action making it a good supplement for diabetic patients - Comes from the Greek word for "color" - A glucose tolerance factor and very important for carbohydrate metabolism - Higher amount found in hair than in serum - Known sources include Brewer's yeast (Saccharomyces cerevisae)

Chromium | Note: The Greek word is "chroma"

- Is incorporated into bone crystals - Able to correct calcium deficiency - Enhances bone formation preventing osteoporosis (has the same action as calcium) - Excess levels showcase the discoloration/mottling of elements in teeth

Fluorine | Note: Not advised to use toothpastes with too much fluoride

- A component of Vitamin B12 which has the same structure with heme - Absorbed by the same mechanisms as iron (jejunum and duodenum)

Cobalt

- Used for steel production - A high dosage is not toxic except when inhaled - Also deposited in the brain of MRI patients (the dye contains trace elements) - A known constituent of several metalloenzymes including pyruvate carboxylase, mitochondrial superoxide dismutase, arginase, and glucokinase

Manganese

Acute manganese aerosol intoxication commonly known as what (2)?

Locura Manganica/Manganese Madness | Note: Is common in younger people

Manganese is a known constituent of several metalloenzymes including pyruvate carboxylase, mitochondrial superoxide dismutase, arginase, and glucokinase What 3 elements can also be used as a replacement for the aforementioned enzymes in cases of manganese deficiency?

Magnesium, Iron, and Copper

- Low levels of this may result in chronic toxicity which resembles Parkinson’s disease, epilepsy, hip abnormalities, joint disease, congenital malformation, heart and bone problems, and stunted growth in children - In cases of liver disease, a decrease in excretion of this element is evident causing an increase of it in the blood

Manganese

This condition in manganese deficiency presents with akinesia, rigidity, tremors, and mask-like faces

Parkinson's Disease (the deficiency only mimics the disease)

- This serves as a basis for the treatment of Wilson’s Disease - It inhibits copper and iron absorption - Is rapidly eliminated in both urine (predominant) and bile - A very important cofactor of xanthine oxidase, xanthine dehydrogenase, sulfite oxidase, and aldehyde oxidase

Molybdenum

Molybdenum is a necessary cofactor for the function of xanthine oxidase, xanthine dehydrogenase, sulfite oxidase, and aldehyde oxidase which forms what complex?

Molybdopterin complex

# What kind of Molydenum deficiency? 1. Is rare, with a single case reported as a result of total parenteral nutrition in a man with Crohn’s disease 2. A recessively inherited error of metabolism due to a lack of functional molybdopterin

1. Dietary Molybdenum Deficiency 2. Molybdenum Cofactor Deficiency

# What kind of Molydenum deficiency? Symptoms include seizures, anterior lens dislocation, decreased brain weight, and usually death prior to 1 year of age

Molybdenum Cofactor Deficiency

- This is rarely reported as there are few known cases of human exposure to excess molybdenum - High exposures have been linked to elevated uric acid in blood (increased gout incidence)

Molydenum Toxicity

- This is naturally present in soil (root crops and vegetables) - A very important component of glutathione peroxidase in the form of selenocysteine - Known to regenerate Vitamin E and C - Involved in the metabolism of thyroid hormones (e.g. deiodinase enzymes and thioredoxin reductase)

Selenium

This is an enzyme that plays a part in cellular antioxidant defense mechanisms against free radicals to which selenium is a component of

Glutathione Peroxidase

# Evolution of Selenium - In the 1930's, it was a ____ - In the 1940's, it was a ____ - In the 1950's, it was declared as an ____ - In the 1960's to 1970's, it was viewed as an ____

1. Toxic element 2. Carcinogen 3. Essential element 4. Anticarcinogen

- Acute oral exposure may produce gastrointestinal and cardiovascular symptoms - Chronic oral exposure can cause dermal effects and neurological problems

Selenium Excess

# Acute or Chronic Exposure (Selenium)? Gastrointestinal symptoms (nausea, vomiting, and diarrhea) and cardiovascular symptoms (tachycardia)

Acute

# Acute or Chronic Exposure (Selenium)? Dermal effects (diseased nails and skin and hair loss) and neurologic problems (unsteady gait or paralysis)

Chronic

- An endemic cardiomyopathy that affects mostly children and women of childbearing age in certain areas in China - Has also been associated with the resultant increased virulence of the coxsackievirus (destruction of cardiac cells)

Keshan Disease (Selenium Deficiency)

- An endemic osteoarthritis that occurs during adolescent and preadolescent years especially in North China, North Korea, and Eastern Siberia - Presents with chondronecrosis (necrosis of cartilage)

Kashin-Beck Disease (Selenium Deficiency)

What are the 2 diseases under Selenium Deficiency?

1. Keshan Disease 2. Kashin-Beck Disease

# Identify the Trace Element(s) Absorbed in the duodenum and jejunum

Iron and Cobalt

# Identify the Trace Element(s) Absorbed in the stomach and intestines

Copper

# Identify the Trace Element(s) Intoxication is rare or very little evidence points to toxicity when high amounts are present in the system

1. Zinc 2. Manganese (EXCEPT when inhaled)

# Identify the Trace Element(s) Exposure to fumes and dust can be toxic (has an aerosol exposure route)

1. Zinc 2. Manganese

# Identify the Trace Element(s) Has ionic states

1. Iron (+2 and +3) 2. Copper (0 to +3)

# Identify the Trace Element(s) Has something to do with the heme molecule

1. Iron 2. Cobalt

# Identify the Trace Element(s) Can be stored in the liver

1. Iron 2. Copper

# Identify the Trace Element(s) Wilson's Disease

Copper (excess)

# Identify the Trace Element(s) Menke's Kinky Hair Syndrome

Copper (deficiency)

# Identify the Trace Element(s) Locura Manganica

Manganese

# Identify the Trace Element(s) Increased Zinc Absorption

Copper (deficiency)

# Identify the Trace Element(s) The basis for the treatment of Wilson's disease

Molybdenum

# Identify the Trace Element(s) Excreted through the bile

1. Copper 2. Molybdenum

# Identify the Trace Element(s) Glutathione Peroxidase

Selenium

# Identify the Trace Element(s) Was initially considered a carcinogen

Selenium

# Identify the Trace Element(s) Has an oral exposure route

Selenium (excess)

# Identify the Trace Element(s) Keshan Disease

Selenium (deficiency)

# Identify the Trace Element(s) Kashin-Beck Disease

Selenium (deficiency)

# Identify the Trace Element(s) Has an inversely proportional relationship with each other

Zinc and Copper

# Identify the Trace Element(s) Involves diseases/disorders that are inherited

1. Copper (Menke's Kinky Hair) 2. Molybdenum (Molybdenum Cofactor Deficiency) 3. Zinc (Acrodermatitis enterophatica)

# Identify the Trace Element(s) Acrodermatitis enterophatica

Zinc

# Identify the Trace Element(s) Brewer’s yeast or Saccharomyces cerevisiae

Chromium

# Identify the Trace Element(s) Mimicry of Parkinson's Disease

Manganese