Minerals Dra Alcantara

BIOCHEM B Minerals Dra Alcantara Definition:  4% of total body weight  Plays a vital role in the different metabolic processes in the body  Inorganic compounds  No carbon structure  No caloric value  Remain as ash when completely burnt  Divided into two: o Macrominerals o Microminerals

MINERAL BIOAVAILABILITY  Physiologic need for a particular mineral at the time of consumption  Amount of substance that reaches the circulation readily available for metabolic processes  Bioavailability of the body will depend on the physiologic need of the individual (↑need  ↑absorption of specific mineral) Bioavailability will be affected by: Mineral-Mineral Interaction E.g. VERY HIGH IRON LEVEL Transport mechanism of iron: TRANSFERRIN ZINC also uses Tranferrin. IRON: primary mineral that uses transferrin

MACROMINERALS/BULK ELEMENTS  RDA: 100mg or more Cations (+)  Calcium  Magnesium  Sodium  Potassium Anions (-)  Chloride  Sulfate  Phosphorus MICROMINERALS/TRACE ELEMENTS  RDA: <100mg Essential Trace Elements  Capable of homeostatic control  Can be controlled by means of their level in the body  Whenever it is already of toxicity, the body has something to do about all those minerals so that you will not attain toxicity until a certain level only  Cations (+): o Iron o Zinc o Manganese o Copper o Cobalt o Nickel o Vanadium o Tin o Molybdenum o Selenium o Chromium o Silicon  Anions (-): o Iodine o Fluoride Non-Essential Trace Elements  Presence of it in the body would already indicate toxicity o Lead o Mercury

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Bernabe, Maria Katrina (2013)

High Fe level  Less transferrin that will carry ZINC to other parts of body Both of these minerals (Fe and Zn) compete with the same transport system (TRANSFERRIN). Fiber - Mineral Interaction  Calcium can be affected by the level of fibers in the body coming from cereals and plants E.g. PHYTIC ACID o From plants o Tries to bind with calcium Phytic acid + Ca = Non-absorption of Calcium Vitamin-mineral interaction  Fe can be enhanced in terms of reduction FERROUS STATE: absorbable form of Fe Before Ferric can be reduced to Ferrous state, the conversion will be enhanced by the presence of VITAMIN C. There will be more IRON absorption in the presence of vitamin C. 

The specific vitamin that affects calcium is VITAMIN D.

GENERAL FUNCTIONS  Structural o Calcium, Phosphorus: main components of skeletal system 

Acid - base balance o Cl, P, PO4, K

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Neuromuscular irritability (excitability) o ↓Ca = ↑ irritability, excitability o ↑Ca = ↓ irritability, excitability

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As constituents of hormones o Iodine: used in the synthesis of T3 & t4 o Chromium: potentiates activity of insulin

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Co-factor for catalytic activity o Chloride: used by Amylase o Zinc: used by Carbonic anhydrase o Copper & Iron: used by Cytochrome

CHROMIUM

 Important component of stainless steels and metal alloys  Cr(III) is an essential dietary nutrient

FUNCTIONS:  Carbohydrate metabolism o constituent of the “glucose tolerance factor” (GTF) GTF

IRON 2 IONIC STATES OF IRON:  Ferrous iron (reduced) Fe++ o Absorbable form of Fe  Ferric iron (oxidized) Fe +++ o Used for storage and transport o Binds with Ferritin for storage 2 FORMS OF DIETARY IRON  Heme iron o derived from flesh of animals (MFP) M – Meat F – Fish P – Poultry  Non-heme o iron derived from plants

 Facilitates reaction of insulin  Will try to potentiate/facilitate the action of insulin

Thereby, if insulin causes blood sugar to decrease, Chromium then is also capable of decreasing the sugar level by means of GTF (increasing/ potentiating the action of insulin) That is the reason why chromium is used as an alternative agent to treat diabetes (together with zinc). But insulin is still better because you are already giving the hormone so the effect is already direct. If there is no insulin, chromium will have no effect. 

Cholesterol metabolism o stimulation of synthesis of fatty acids (↓ LDL and ↑ HDL) o beneficial to those with atherosclerosis and diabetes

MOLYBDENUM

 can be used as co-factor for different oxidase enzymes  constituent of specific enzymes: (“Molybdenum cofactors”)

XANTHINE OXIDASE  oxidation of purines and pyrimidines and the production of uric acid  Conversion of: Hypoxanthine  Xanthine  Uric acid ALDEHYDE OXIDASE  oxidation of aldehydes SULFITE OXIDASE  involved in the metabolism of sulfur amino acids  oxidation of amino acids containing the sulphur group (Cysteine, Methionine)

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You have your heme and non-heme component.

Entering the Cytoplasmic Area: Heme could readily enter or be absorbed in the brush border or cytoplasmic area by means of HCP1 (Heme Carrier Protein 1). Non-heme has a Ferric iron (Fe3+). The non-heme will give you the oxidized form of iron (Fe2+). For it to be absorbed, Ferric needs to be reduced to Ferrous iron. 

Enzyme responsible: FERRIC REDUCTASE (also known as Duodenal Cytochrome B or “Dcytb”).

Ferrous can now be readily absorbed but it needs a carrier called Divalent Metal Transporter 1 (DMT 1). Heme Carrier: Non-heme Carrier:

HCP1 DMT1

Inside intestinal mucosa: You have now here your ferrous and heme. HO-1 (Heme Oxygenase 1): Enzyme responsible to release the ferrous component of heme. Ferrous needs to be oxidized again to Ferric because it is ferric that binds with FERRITIN for storage. Those that remained to be ferrous will go to the circulation. Into the circulation: These (ferrous) will be carried from the intestinal mucosa to the circulation by FPN (Ferroportin).

Q:

If ever Fe is not needed in the circulation because there is adequate amount already, FPN will be down-regulated by HEPCIDIN.

If there is too much Fe in the blood, do I still need transferrin to function (distribute the other Fe to the different parts of the body)?

A:

NOT ANYMORE. ↑ Fe level  ↓ Transferrin activity

Ferroportin: Hepcidin:

carrier down regulator of FPN

Too much Fe level, there will be stimulation of hepcidin  Hepcidin down regulates Ferroportin  (-) Ferroportin  () Fe will go into the blood because Ferroportin is the carrier.

Circulation: There is now ferrous in the circulation. Ferrous needs to be oxidized again into Ferric because it is Ferric that binds with TRANSFERRIN. HEPHAESTIN (Hp)  Enhances the conversion of Ferrous to Ferric  Contains the enzyme FERROUS OXIDASE  Could only function in the presence of Copper  Is copper dependent Summary of the CHONs working in the transport of Fe: 1. HCP1 2. DMT1 3. Ferric Reductase/Dcytb (enhanced by Vit C) 4. Heme Oxygenase (HO-1) 5. Ferritin 6. Ferroportin (FPN) 7. Hepcidin 8. Hephaestin 9. Transferrin (transports Fe into the circulation) HEPCIDIN  “master regulator of iron homeostasis”  Down-regulates ferroportin  Encoded by HAMP gene  Composed of 25 amino acids  hemojuvelin

↑ Hepcidin  ↓ Ferroportin  ↓ Fe level Q:

During inflammatory conditions, you have seen a patient looking pale. There are no bleeding tendencies or trauma but the Hgb is low. Why? Fe is needed for heme synthesis There is pallor because there is inflammation within the body. Inflammation stimulates Hepcidin  High hepcidin  decreased ferroportin  decreased iron

A:

Q: A:

What if there is increased RBC synthesis? ↑RBC synthesis  inhibit Hepcidin  ↑ Ferroportin  ↑availabilty of Fe

FACTORS THAT ENHANCE NON-HEME ABSORPTION  ↑ Conversion of Fe3+  Fe2+  ↑ Activity of Ferric Reductase 1.

2. 3. 4.

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”MFP” factor o factor that promotes the absorption of non-heme iron from other foods eaten at same meal Ascorbic acid Citric acid and lactic acid from foods Hydrochloric acid in the stomach o This is the reason why Fe should be taken on an EMPTY STOMACH so that hydrochloric acid will be high then there will be better absorption of Fe. Sugars

FACTORS THAT INHIBIT IRON ABSORPTION  Inhibit conversion of Fe3+  Fe2+ 1. 2. 3. 4. 5.

Phytates and fibers (grains and vegetables) Oxalates (spinach) Calcium and phosphorus (milk) EDTA (food additives) Tannic acid (in tea and coffee)

ZINC FUNCTIONS  It is absolutely required for normal spermatogenenesis, fetal growth, and embryonic development (↓Zn  Dwarfism)  Prevents prostatic CA (males)  Boost immune system (stimulates leukocytes)  Boost brain activity (adds a little intelligence; because intelligence is more of genetics)  Synthesis and action of insulin (like Chromium)  Stabilizes membrane structure by preventing lipid peroxidation and reducing free radical formation (ANTIOXIDANT)  Component of GUSTIN, a salivary protein that has an ability to increase appetite  Zinc and PMS (↑Zn  ↓PMS)  Involved in the synthesis and stabilization of proteins, DNA and RNA and plays a structural role in ribosomes and membranes.  Necessary for the binding of steroid hormone receptors and several other transcription factors to DNA (steroid synthesis)  As Co-factors of enzymes: o PT  Peptidases  Thymidine Kinase o CLAS  Carbonic Anhydrase  Lactate DH  Alkaline Phosphate  Superoxide Dismutase

2 ways to regulate: 1. Regulate its entry into the plasma membrane 2. Regulate its entry and exit into Zincosomes 2 Zinc Transporters: 1. ZnT (Zinc Transporter) 2. ZIP (Zinc Protein) PLASMA MEMBRANE  ZIP carries Zn IN to plasma membrane  ZnT carries Zn OUT of the plasma membrane ZINCOSOMES  ZnT going IN to the zincosomes  ZIP going OUT of the zincosomes METALLOTHIONEIN  Binding CHON for ZN and Cu  a special binding protein that regulates the amount of zinc that is released in the blood

If body does NOT need zinc

If body NEEDS zinc

Zinc is incorporated into intestinal metallothionein

Zinc is incorporated into intestinal metallothionein

Zinc SLOUGHED OFF with intestinal cells

Zinc is transported into BLOOD STREAM

PROSTATE GLAND:

ZINC HOMEOSTASIS

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 Zn could enter into the plasma membrane or into the zinncosomes.

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Zn will ↑ apoptosis in 2 weeks by 2 ways. Zn will try to stimulate BAX GENE as well as activate CYTOCHROME C (stars in the photo above) Release of Cytochrome C will stimulate CASPACE CASCADE. Caspace cascade promotes APOPTOSIS Apoptosis  death of cell  no chance for that cell to proliferate

Thereby, if you have prostate CA and a Zn that will promote apoptosis, then there will be aa lesser chance for this prostate to increase in size.

6. 7.

ZINC DEFICIENCY  Severe growth retardation - Dwarfism  Arrested sexual maturation  Hinders digestion and absorption leading to diarrhea because (-) regeneration of mucosa

Blood clotting o Especially Factor VII ANS function o TYROSINE HYDROXYLASE

TRANSPORT

Q: Can Zn be given to patients with diarrhea? A: YES, because this will treat the mucosa to regenerate faster.   

Impaired immune system Poor motor development and performance Impaired sense of taste (GUSTIN)

cognitive

ZINC INTERACTION WITH IRON  Zn level will be dependent on the Fe level because Zn and Fe competes with transferrin  Some plasma zinc binds to transferrin  If there is too high zinc intake, there is no more transferrin to bind with iron, hence, impairs its absorption. ZINC INTERACTION WITH COPPER  Zn will also be dependent on the level of Cu  Copper and zinc compete for binding with metallothionein  Metallothionein binds strongly with copper 2 MINERALS THAT AFFECTS THE LEVEL OF ZINC: o Iron o Copper

COPPER

 Antioxidant  highest concentrations are in the liver, brain, kidneys, heart and skeletal muscle  90% bound as CERULOPLASMIN  transported to other tissues mainly by ALBUMIN  found in enzymes (co-factor)

FUNCTIONS [COPPER-DEPENDENT ENZYMES] 1. Iron utilization o oxidation of iron o FERROUS OXIDASE 2. Antioxidant o removal of superoxide radicals o SUPEROXIDE DISMUTASE 3. Development of bone and connective tissues o synthesis of collagen and elastin o LYSYL OXIDASE 4. Melanin production o converts tyrosine to melanin o TYROSINASE 5. Energy metabolism o ETC/formation of ATP o CYTOCHROME ENZYME

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hCTR1 (Human Copper Transporter 1)  carrier of Cu into cell membrane From the plasma membrane, Cu will then be taken in by:  COX17 to the mitochondria  ATOX1 to trans-Golgi network  CCS to Copper-Zinc-Super Oxide Dismutase (CuZnSOD)  As part of Glutathione component to be linked to the transporter Metallothionein In the trans-Golgi network, the ATP-7B GENE has 2 functions: 1. Could give again the Cu and transport it out into the biliary circulation (excretion) 2. Bind the Cu to become Holo-ceruloplasmin so that Cu can go outside the membrane and be part of the circulation COPPER DEFICIENCY  Copper is widely distributed in foods so a deficiency is not common but may occur in premature infants or in malnourished patients repleted with low copper diet  MENKE’S DISEASE o kinky or steely hair syndrome o Copper binding P- type ATPase(Efflux) o X- linked, male infants o Nervous system, vessels, connective tissue o MR, DEC Cu, dec CP COPPER TOXICITY  Defective ATP78 gene  Acute Toxicity o ingestion of >15 mg elemental Cu

Causes  N&V  Diarrhea  Abdominal cramps  Chronic Toxicity (WILSON’S DISEASE) o Rare inherited disease o Free tissue copper & total liver copper are increased o Excess Cu is stored in the liver, brain & cornea of the eye o PENICILLAMINE o

ANTIOXIDANTS Enzymatic Antioxidants  SUPEROXIDE DISMUTASE o metalloCHON containing Cu, Zn, Se, Mn Types of superoxide dismutases in humans:  Copper, Zinc o Cytosol o Mitochondrial intermembrane space o Extracellular space  Manganese o Mitochondrial matrix  Selenium o Part of glutathione component

IODINE T3-T4 METABOLISM 1. IODIDE TRAPPING o Is Na-K ATPase dependent o Without Na, Iodide cannot cytoplasmic area 2.

OXIDATION o Hydrogen peroxide (oxidizing agent used) is produced by a NADPHdependent enzyme o PEROXIDASE: Enzyme used for oxidation of iodine IODIDE

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PEROXIDASE

IODINE

ORGANIFICATION o Iodine will bind to tyrosine o Aka IODINIFICATION TYROSINE + IODINE  IODOTYROSINE Enzyme: IODINASE

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COUPLING MECHANISM o MIT (MONOiodotyrosine) – 1 o DIT (DIiodotyrosine) - 2 MIT + DIT  T3 DIT + DIT  T4

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PROTEOLYSIS DEIODINATION

Bernabe, Maria Katrina (2013)

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SECRETION OF T3 AND T3 o Recycled; or o T3 and T4 will be released into the circulation

SUMMARY OF EFFECTS OF IODINE  ↑ Iodine  ↑ Heat production  ↑ O2 consumption  ↑ metabolic rate  ↑ Thyroid Hormone  ↑ Food Utilization  ↑ Appetite, but HIGH BMR  Thin figure  ↑BMR  ↑ needed ATP (to provide energy to such metabolic processes)  In order to produce HIGHER ATP  ↑size and number of mitochondria  Higher ATP

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↑ Glycolysis (due to ↑ need for ATP) Rapid uptake of glucose by cells CHON: ↑ CHON synthesis FATS: ↑Lipogenesis < ↑Lipolysis VIT: Convert Carotene  Vit. A

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HYPERTHYROIDISM  “Lahat mabilis” HYPOTHYROIDISM  “mabagal”

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CHO:

IODINE DEFICIENCY OR GOITROGENIC FOODS  Cassava, corn, bamboo-shoots, sweet potatoes, Turnips, cabbage, garlic and onions o Higher tendency of IODINE deficiency because all of these will try to inhibit iodide trapping (1st step); therefore, T3 and T4 are not produced

CALCIUM     

Most abundant mineral in the body 1.5 to 2% of body weight Main structural component of bones and teeth 99%: OH apatite [Ca10(PO4)6(OH2)]form 1% - in extracellular fluids (ionized form)

3 ORGANS INVOLVED IN CALCIUM HOMEOSTASIS

↑Ca DEPOSITION(bones) ↓Ca uptake (intestines) ↓Ca reabsorption from urine

CALCITONIN

PTH

↑Ca RELEASE (bones) ↑Ca uptake (intestines) ↑Ca reabsorption from urine

ABSORPTION OF CALCIUM INCREASE Body need Healthy adults: 10-40% dietary calcium

DECREASE overall Ca

INCREASE overall Ca

DECREASE Binders: Oxalic acid in beets, rhubarb, spinach Phytates in seeds, nuts

Growing children, pregnant and lactating mothers >40% Lactose Vitamin D Induces the synthesis of calbindin Gastric acidity PTH Amino acids: Lysine/Arginine/Serine

Excess PO4 Vitamin D deficiency Lack of gastric acid Calcitonin Lack of exercise Dietary fat High fiber intake and laxatives

SELENIUM FUNCTIONS  Selenium is an essential component of the body’s antioxidant defense system. Part of the enzyme Glutathione peroxidase, which catalyzes the breakdown of toxic hydroperoxides.  Component of the enzyme that converts T4 to T3 (Iodothyronine Deiodinase) Vitamins that Convert T3  T4: 4 ANTIOXIDANT Minerals:

Selenium & Iodine Cu, ZN, Mn, Se

SAMPLE QUESTIONS: Copper plays as an integral part of which of the following enzymes: A. Cytochrome-C oxidase B. Ferrous oxidase C. A and B D. None of the above Calcium absorption is increased by: A. Phytic acid B. Gastric acid C. Oxalic D. ALL

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Zinc absorption can be decreased by which of the following: A. Iron content of the body B. Magnesium C. Both A and B D. None of these True of Iron A. Increase iron level increases Transferrin B. DCYTB has a ferrous reductase activity C. Increase hepcidin level increases iron absorption D. A and C E. A and B Minerals serve as co-factor in different enzymes. Which of the following is correctly paired? A. Molybdenum – Xanthine Oxidase B. Copper – Carbonic Anhydrase C. Zinc – Amylase D. Chloride – Superoxide Dismutase Zinc level in the prostate gland is said to be preventive of prostate cancer. Which of the statements below describe/s such principle: A. Zinc stimulates expression of BAX gene that increases caspase cascade activity B. Zinc decreases cytochrome C release to increase apoptosis C. A/B D. None of the above Copper can be distributed in its subcellular location in the body thru copper chaperons. Which of the following then is/are correctly paired? A. COX 17 – Mitochondria B. ATOX 1 – ZnCuSOD C. CCS – trans golgi apparatus D. A/B E. All of the above Calcium level can be controlled by hormonal regulation. Which of the following is/are true then regarding this/these hormones? A. Vitamin D increases intestinal and renal absorption of calcium B. Calcitonin increases delivery of calcium in the bones C. A/B D. None of the above Ca could directly activate which of the following enzymes: A. Lipase B. Adenosine triphosphatase C. Glycogen synthase D. A and B Absorption of iron is regulated by: A. Ferroportin B. Hepcidin C. Level of Transferrin D. A and C E. All This is the function of chromium A. Forms bone and teeth B. Bone metabolism and enzyme reaction C. Utilization of glucose