MICRONUTRIENTS AND HEALTH OF THE POPULATION - PowerPoint Presentation

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MICRONUTRIENTS AND HEALTH OF THE POPULATION

BYRAHAMON, Sheu K. (139735)

M.Sc. Seminar Presentation 2008

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MICRONUTRIENTS AND HEALTH OF THE POPULATION by Rahamon SK

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OUTLINE

IntroductionDefinition of micronutrientsFunctions of micronutrientsConclusionReferences2

M.Sc. Seminar Presentation 2008

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WHAT IS HEALTH?

Health can be simply defined as a state of complete physical, mental and social wellbeing and not merely the absence of disease or infirmity (WHO, 1980). Achieving health and remaining healthy is an active process that requires effective strategies like good nutrition, exercise and hygiene among others.

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Appropriate intake of micronutrients is required to maintain optimal health.

Inadequate intake is recognized as an important contributor to the global burden of disease through increased rates of illness, death from infectious diseases, and of disability such as mental impairment (Ezzati et al., 2002).

Deficiencies of micronutrients have been associated with various pathologies such as hypertension (Chiplonkar et al., 2004), cancer (Gross, 2005), fetal growth retardation (Scholl et al., 2000), and iodine deficiency disorders (Boyages

, 1993) among others.

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M.Sc. Seminar Presentation 2008

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MICRONUTRIENTS

“Micronutrients” is the collective term applied to essential vitamins and minerals (WHO, 2003).Micronutrients comprise dietary minerals (inorganic) and vitamins (organic). Each interacts through a complex metabolic network essential for maintaining optimal health (van

Ommen et al., 2008).Inorganic micronutrients can be classified into two groups:

- bulk minerals: C, H, O, N, S, Ca, P, K, Na, Cl -essential trace elements: Cu, Fe, Mg, Zn,

Mn, Mo, Co, Cr, I, F, Se.

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Table 1. Trace elements and some enzymes in which they serve as cofactors

Copper Cytochrome

C oxidaseSuperoxide dismutase

CeruloplasminTyrosinase

Dopamine β-

hydroxylaseLysyl oxidaseDiamine oxidase (AbdulRazzaq et al., 2004)

ZincAlkaline phosphataseSuperoxide dismutaseCarboxypeptidases

Liver alcohol

dehydrogenase

Carbonic

anhydrase

etc

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Iron

CatalaseCytochrome oxidase

Aconitase etcSelenium

Glutathione peroxidase

Deiodinase

Thioredoxin reductase5-LipoxygenaseMolybdenumXanthine oxidase and other related

oxidasesManganese Isocitrate dehydrogenase

Gluconolactone

hydrolase

6-phosphogluconate

dehydrogenase

Magnesium

Transketolase

Acyl-Coa

synthetase

Hexokinase

Glucokinase

Nickel

Urease

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Table 2. Other minerals and their functions

MICRONUTRIENTFUNCTIONS

CalciumSkeletal mineralizationBlood coagulation

Neuromuscular conductionChromosome segregation

Excitability of skeletal and cardiac muscle etc

ChlorideProduction of HClCellular pump functionsCobalt Component of B

12PhosphorusA component of boneEnergy processing and other functions

Potassium

Systemic electrolyte

Essential in

coregulating

ATP with sodium

Sodium

Systemic electrolyte

Essential in

coregulating

ATP with potassium

Sulfur

Component of

cysteine

and

methionine

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VITAMINS

Vitamins are organic compounds required as nutrient in tiny amounts by an organism (Lieberman et al., 1990). They are not synthesized in sufficient quantities or not even synthesized at all (vitamin C in man) hence, must be obtained from the diet.

They are classified as either:water-soluble (B & C) or fat-soluble vitamins (A, D, E & K).

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Table 3: Vitamins and their functions

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VitaminFunctionDeficiency Symptoms

SourcesA (A

1, A2)

Constituents of visual pigmentsFor fetal developmentFor cell developmentNight blindnessDry skinYellow vegetables and fruit

B1 (thiamin)Cofactor in decarboxylation

Beriberi

Neuritis

Liver

Milk

B

2

(riboflavin)

Constituent

of

flavoproteins

Glossitis

Cheilosis

Liver

Milk

B

3

(niacin)

Constituent of NAD

+

and NADP

+

Pellagra

Yeast

Lean meat

Liver

B

6

(pyridoxine)

Prosthetic group of certain

decarboxylases

and

transaminases

Convulsions

Hyper-irritabilityYeastWheatCornLiverPanthotenic acidConstituent of CoADermatitisEnteritisAlopeciaAdrenal insufficiencyEggsLiverYeast

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Biotin

CO2

fixation in fatty acid synthesisDermatitisEnteritis

Egg yolk

LiverTomatoes

Folic acidCoenzymes for “1-carbon” transferSprueAnemiaNeural tube defects

Leafy green vegetablesB12 (cyanocobalamin)

Coenzyme in amino acid metabolism

Stimulates

erythropoiesis

Pernicious

anaemia

Liver

Meat

Eggs

Milk

C

(ascorbic acid)

Maintains prosthetic ions in their reduced form

Scavenges free radicals

Collagen synthesis

Scurvy

Citrus

Fruits

Leafy green vegetables

D group

Increase intestinal absorption of Calcium and Phosphate

Rickets

Fish liver

E group

Antioxidants

Ataxia and other signs of spinocerebellar dysfunction

Milk

Eggs

Meat

Leafy vegetables

K group

γ

carboxylation of glutamic acid residues

Hemorrhages

Leafy green vegetables

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SOME FUNCTIONS OF MICRONUTRIENTS

Micronutrients act as hormones, cofactors, coenzymes, antioxidants, transcription control factors (Zn fingers) and regulators of hormones activities among others. The functions are to be considered in the context of an integrated perspective (van Ommen

et al., 2008). 12

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Figure 1: Health space as defined by metabolic profiles.

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MICRONUTRIENTS AS COFACTORS

Trace elements are frequently involved: in modulating enzymes activities an integral part of enzymes prosthetic group. Cofactors bind in a transient, dissociable manner either to the enzyme or to a substrate such as ATP (metal-activated enzymes) or serve as prosthetic groups (metallo enzymes) (

Shenkin, 2006).

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MICRONUTRIENTS AS COENZYMES

Coenzymes serve as recyclable shuttles (or group transfer agents) (Murray et al., 2006). Many vitamins or vitamin metabolites are required to play an active part within complex biochemical reactions for example, ribovlafin (FMN, FAD) and niacin (NAD, NADP) in energy metabolism, folic acid in one-carbon transfer (Kammana

et al., 2000; Powers, 2003; van Ommen et al., 2008). These reactions are critical in energy provision, proteins and nucleic acids synthesis.

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Zn as a cofactor

Zn and Osteopetrosis: Zn has been found to be a cofactor for over 300 enzymes (Shenkin, 2006). A typical example is carbonic anhydrase

which catalyses the reaction: CO2 + H2O ↔ H

2CO3 ↔ H

+ + HCO3-

. Reid et al.(1997) reported that there is a positive correlation between Zn intake and bone mineral density. This is due to dependence of carbonic anhydrase on Zn, a deficiency of which can cause osteopetrosis (marble bone disease), a disease characterized by increased bone density due to impaired bone resorption.

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Figure 2: Carbonic

anhydrase in bone resorption

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Copper and Anaemia

Microcytic hypochromic anaemia and anaemia due to impaired collagen synthesis result from Cu deficiency due to its involvement in iron (Fe) transportation and collagen synthesis.

In microcytic hypochromic

anaemia, there is low ceruloplasmin

(which has ferroxidase activity) hence, absorbed Fe cannot be transported out of the intestinal mucosal into the systemic circulation. This leads to

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Cu is also a cofactor for

lysyl oxidase. This enzyme is involved in the modification of certain lysyl residues converting

ε-amino groups to aldehydes.

Since collagen is required for the maintenance of the blood vessels integrity, Cu deficiency results in reduced collagen synthesis which leads to blood loss culminating in anaemia

(Murray et al., 2006).

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Folate, B

6 and B12 as coenzymes Deficiency of B12, B

6 and folate have been associated with several pathologies. Activation of methionine

by ATP is accompanied by vital methylation reactions that allow the synthesis of creatine

and phosphatidyl-choline as well as methylation of DNA, RNA, and a large number of

neuromediators (Durand et al., 2001). The rersulting homocysteine is either:catabolyzed into cystathionine or remethylated

into methionine.20

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Figure 3:

Folate

, B6 and B12 in

homocysteine metabolism

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The

remethylation is catalyzed by methionine synthetase, which uses N5-methyl

tetrahydrofolate as the methyl donor and cobalamin (B12) as the coenzyme.

Homocysteine catabolism is conducted by cystathionine

β-synthase, a vitamin B

6 dependent enzyme, to eventually yield cysteine (a precursor of GSH). The resulting hyperhomocysteinemia can result in thromboembolism (Cattaneo, 1999), coronary artery diseases (Boushley et al., 1995), several cardiovascular diseases (Wald, 2002) etc

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Riboflavin and Niacin

These vitamins are coenzymes in oxido-reduction reactions. Their deficiencies have been reported to cause seborrheic

dermatitis, pellagra, chielosis, reduced energy (ATP) production etc. Riboflavin forms the FAD part of the

flavo-enzyme, glutathione reductase which is responsible for the maintenance of the levels of active (reduced) GSH involved in protein folding, maintenance of reduced pools of vitamins C & E, antioxidant/antitoxin activities (Kidd, 1997).

GSH reductase

GSSG 2GSH NADH + H+ NAD+

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MICRONUTRIENTS AS ANTIOXIDANTS

Much of the popular interest in the micronutrients stems from the recognition that many of the micronutrients have antioxidant properties. Oxidative metabolism leads to generation of reactive oxygen species (ROS) or free radicals which can cause further oxidative reactions, especially to those parts of the cell in a relatively reduced state such as cell membranes and nucleic acids (Evans et al., 2001).

The potential to cause damage is limited by mechanisms that include direct quenching of oxidant activity by chemical antioxidants or enzyme systems (Shenkin, 2006).

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Figure 4: Sources of free radicals

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The total antioxidant capacity of a given compartment is divided into:

preventive antioxidant and, chain-breaking antioxidants (Marit et al., 2000).

Preventive AOs comprise scavenger enzymes e.g. glutathione-S-transferase. They also include metal binding proteins like ferritin, transferrin

, ceruloplasmin and albumin which protect by sequestering transition metals.

Chain breaking AOs such as SOD, GSH, α-tocopherol, uric acid and albumin intercept damaging species (

Seis, 1993; Halliwel, 1994, Rumley et al., 1998). Zn, Se and Cu are considered as AOs due to their presence in SOD and GPx. 26

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Figure 5: Micronutrients and the cell

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SOD

isozymes converts superoxide ion to hydrogen peroxide, which is acted upon by GPx (Se containing enzyme) or catalase (Fe containing enzyme) to yield harmless species. SOD

2O2.- + 2H+ H

2O2 + O

2 catalase 2H

2O2 2H2O + O2 GPx 2H

2O2 2H2O + O2 GSH GSSG

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Vitamin E is the major lipid-soluble AO protecting cell membranes and plasma lipoproteins. It reacts with lipid-peroxide radicals formed by

peroxidation of PUFA (Murray et al., 2006). Synergism between vitamin E and other enzyme antioxidants is shown in Figure 5.

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Figure 5: Vitamin E and enzyme antioxidants

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MICRONUTRIENTS IN HORMONE METABOLISM

Several micronutrients such as Se, Cr, I2 and Cu have been found to be actively involved in hormone metabolism. Synthesis of T3 and T4 requires a rare element, I2 for bioactivity (

Marrit, 2000). Deficiency of iodine has been reported to cause a wide spectrum of illness collectively known as “ Iodine Deficiency Disorders”. Goiter, hypothyroidism, endemic cretinism, fetal wastage, intellectual disability, retarded growth and puberty,

perinatal and infant mortality manifest consequent to I2

deficiency (Hetzel, 1987; Boyages, 1993; UNICEF, 1999).

Thyroxine deiodinase is another vital enzyme in TH synthesis. It is a selenoenzyme that converts T4 to T3 and rT3 to T2. Marit et al. (2000) reported that low plasma Se had an effect on TD activity which manifested as hypothyroidism. 31

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why

Figure 6: Micronutrients in hormone synthesis

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CHROMIUM AND GLUCOSE TOLERANCE

Chromium has been linked with glucose tolerance (Kozlovsky et al., 1986; Anderson et al., 1990; Morris et al., 1993). Anderson et al. (1997b, 2000) and Ghosh

et al. (2002) reported that subjects on higher Cr levels had reduced fasting serum glucose, insulin, total cholesterol, lower 2-hour insulin and glucose concentrations after a glucose challenge, and lower glycated HbA1 levels.

The mechanism of Cr action was linked with chromodulin which interacts with insulin receptors during glucose upsurge (Davis et al., 1996, 1997, Vincent, 2004).

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Cr +

apochromodulin insulin(due to hyperglycaemia)

holochromodulin Insulin receptor Amplified receptor’s kinase

activity Tyrosine

phosphorylation

Complex series of events Figure 8: Chromium in glucose control

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MICRONUTRIENTS AND IMMUNE RESPONSE

Several reports have shown the essentiality of micronutrients in mounting an effective immune response. Reduction in thymulin activity, decreased proliferation of lymphocytes, impaired delayed

cutaneous hypersensitivity, atrophy of lymphoid tissues, and slower neutrophil chemotaxis have been reported in Zn deficient individuals (Chandra, 1980).

Zn supplementation was shown to reduce the incidence of diarrhea and pneumonia (Black, 2003) as well as duration of common childhood infections (

Karyadi et al., 2002). In Cu deficient people, impaired antibody response to

heterologous RBC, low levels of thymic hormone activities, depressed RES function, and depressed granulocyte microbicidal activities are common findings (Vyas et al., 1983). 35

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Beck (1995) reported that

Coxsakie B3 virus injected into Se deficient mice mutated to a more virulent form that may cause cardiomyopathy.Rayman (2002) reported that children with low levels of Se had faster disease progression and mortality.

Increased susceptibility to infections due to impaired phagocytosis caused by Zn deficiency has been linked with reduced production of bactericidal substances during respiratory burst (Murray et al., 2006).

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NADPH

oxidase 2O2 + NADPH 2O2.- + NADP+ H

+ SOD O2.-

+ O2.- + 2H

+ H2O2

+ O2 Myeloperoxidase H2O2 + X- + H+ HOX + H2O

(X- = Cl-, Br- , I- etc)

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Figure 7: Ca, niacin, riboflavin and Zn in

phagocytosis

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CONCLUSION

Micronutrients play a central part in metabolism and in the maintenance of tissue function. An adequate intake is necessary to prevent micronutrients deficiency which stands as an underlying cause of increasing morbidity and mortality especially in the developing world. Everybody is therefore, expected to envision an effort channeled towards disease prevention rather than cure.

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REFERENCES

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Thanks for listening

.

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MICRONUTRIENTS AND HEALTH OF THE POPULATION by Rahamon SK

is licensed under a

Creative Commons Attribution-

NonCommercial

-

ShareAlike

4.0 International License