MINERAL METABOLISM

Macro Elements
Ca, Mg, Na, K, P, Li,S, Cl
60 80% of inorganic compound in the body

Micro Elements

Very small amounts in the body Essentials: Fe, Zn, Cu, Mn, I, Mo, Co, Se, Cr Suspected essentials are Ni, F, Br, As, Va, Cd, Ba, Sr Non-essentials are Al, Hg, Ag, Pb, Ge

Calcium
+ 99% of body calcium is as hydroxyapatite in the

skeleton
Adult requirement: 0.5-1.0 mgCa/day Absorption of it is decreased by Lack of vit.D excess of phytates

low Ca/P ratio in diet

Biological function of calcium

1.

excitability of nerve function, neural transmission, & contraction of muscle.

Activation of prothrombin in blood coagulation process transfer of ions across cell membranes and release of neurotransmitters at synaptic junction release of cellular enzymes (e.g. amylase), activition of intracellular enzymes (isocitric dehydrogenase, phosphorylase; kinase,phosphofructokinase) Regulation of secretion of pituitary hormones, parathyroid hormone, calcitonin and vasopressin

2. 3.

4.

5.

CALCIUM HOMEOSTASIS
Normal blood values: 9.5-10.5 mg/100 ml 35-45% bound to proteins (mostly albumin) In extracellular fluid is main ionized form (55 - 65%) 0,5mg (5-10%) is jointed to organic acid, phosphate,

citrat, ect.
Ca metabolism is influenced by Parathyroid hormone (PTH) Calcitonin (CT) Vitamin D

HORMONAL CONTROL OF CIRCULATING CALCIUM

Decrease in plasma Ca2+
Stimulation of PTH secretion Kidney: 1. Increased Ca2+ resorption 2. Increased synthesis of 1,25 (OH)2D3 Bone: Increased Ca2+ resorption

Intestine: Increased Ca2+ absorption

Increased in plasma Ca2+ Calcitonin secretion

Phosphorus
+ 15% of it is in muscle and other soft tissues & +

85% is in bone
is an integral part of macromolecules (e.g.

phospholipids, phosphoproteins and nucleic acids)

is absorbed easily and rapidly (70%) Its excretion is equivalent to dietary phosphate intake

maintenance of skeletal mineral structure and buffer

system
Is required for transport of fatty acids, vitamin,

enzyme system and muscle energy metabolism

IRON
Is a component of Heme (Fe2+, 75%of total) IN Hb & myoglobin Cytochromes a, b, & c Is transported (transferrin) & stored (ferritin &

hemosiderin) in Fe3+ form Is absorbed in upper small intestine (10% from diet) Absorption is increased by ascorbic acid Absorption is inhibited by vegetable fiber Iron deficiency results in: Defective erythropoiesis Anemia (normocytic or microcytic)

Zinc
Is an integral part of numerous enzymes

associated with

Carbohydrate & energy metabolism Protein synthesis & degradation Nucleic acid synthesis Intracellular transport functions Protection of cells from oxidative damage

Plays a role in maintaining exocrine & endocrine

pancreatic function
Spermatogenesis is a zinc-dependent process based on

the metals role in testosterone metabolism

Zinc
Absorption of Zn is an active process & shares gut

transport mechanisms wit copper & iron (is bound to metallothioneine)

Its excess interfere with copper absorption Zn loss in renal disease is due to its association with

plasma albumin
Zn deficiency is characterized by Growth retardation Skin lesions Impairment of sexual development, taste & smell Delay of wound healing

COPPER
Associated with several oxygenase enzymes

(cytochrome oxidase, SOD, ceruloplasmin & lysyl oxidase) SOD is scavenging of superoxide & other reactive axygen spacies Lysyl oxidase is related with cross-linking of collagen Its absorption is bound to metallothioneine
Excess cause liver cirrhosis Acute toxicity is manifested by marked Hemolysis Damage to both liver and brain cells

COPPER
Deficiency results in Anemia microcytic hypochromic (pale erythrocyte)

resistent to iron therapy (related to ceruloplasmin) Reduction in number of leukocytes Degenerative of vascular tissue with bleeding (due to defects in elastin & collagen prodcution)

MINERAL & METABOLIC DISORDERS

Zinc
stabilizes cell membranes Zinc (metalloenzymes): a component of cysteine residues, in organelle membranes and polyribosomes is a enzyme cofactor cofactor for RNA and DNA polymerase involved in synthesis of DNA, RNA & ribosomes

required for gene expression, cell differentiation and cell replication. needed for cell mitosis and cell proliferation in wound repair

Functions of zinc in humans: cell growth/proliferation

sexual maturation/reproduction dark adaptation/night vision gustatory acuity wound healing host immune defenses

protects against ultraviolet (UV) radiation (Topical zinc, in the form of divalent zinc ionsprovide antioxidant photoprotection for skin). enhances wound healing contributes to immune and neuropsychiatric functions decreases the relative risk of cancer & cardiovascular disease (metalloenzymes: superoxide dismutase).

Zinc

Zinc
+ 2 to 3 g zinc stores: + 1/5 is in bone + 1/2 is in the liver. the remain in the skeletal muscle. Serum binding: + 55% albumin + 40% to an -acroglobulin (a zinc metalloprotein). Zinc is lost: in fistula output 12 mg/l in diarrhea 17 mg/l. In sweat up to 1 mg zinc per liter skin losses become important with dermatologic

patients or those with burns

 Zinc losses increase in: Diseases: sickle cell anemia, malignancies, diabetes, inflammatory or infectious conditions Medications: estrogens, caffeine, theophylline, & corticosteroids. Short-term zinc depletion greatly influences serum testosterone concentrations seminal volume total seminal zinc loss per ejaculate. Daily absorption: + oral zinc is absorbed in the duodenum and proximal jejunum. copper and iron may suppress zinc absorption. vitamin D may increase zinc bioavailability In zinc deficiency: decreases fibroblast proliferation and collagen synthesis impairs cellular and humoral immunity impairs growth, protein and DNA synthesis and cell division.

Sites of absorption of nutrients within gastrointestinal tract:

Zinc deficiency
On of ten biggest factors contributing to burden of

disease in developing countries Zinc interventions could reduce child deaths globally by 63% South East Asia and Sub-Saharan Africahighest risk of zinc deficiency:
Inadequate intake 1/3 of the population Stunting 40% of pre-schoolers

Inadequate Zinc deficiency Few global policies or recommendations for interventions Zinc used as a (part of) curative intervention for severe malnutrition and diarrhea

Zinc deficiency signs and symptoms:

alopecia - diarrhea glucose intolerance - hypospermia impaired chemotaxis - night blindness depression - apathy delayed wound healing - skin lesions dermatological anergy - growth retardation impaired taste immunological impairment hypogonadism hypospermia mental depression

Iron
is required for hydroxylation of proline and lysine severe iron deficiency can result in impaired collagen production. As a part of oxygen transport system. iron deficiency can result from blood loss infectious causes malnutrition hematopoietic disorder.
Cellular respiration, ATP storage using iron-coupling

reactions

Iron
Possibly T-cell immunity and cognitive function

actions may require iron.

Iron deficiency results in a slight decrease in forming T

cells and a significant impairment of lymphocyte response to mutagens and antigens.

Toxicity (hemosiderosis) mainly as a result of saturation of hemosiderin stores can result from multiple blood transfusions, because

blood contains about 0.5 mg iron/ml.

Iron deficiency
Categorized as one of top ten most serious

health problems in the modern world (WHO) As many as 4-5 billion people (66-80% of population) may be iron deficient 2 billion people (>30% of population) are anemic Iron deficiency is associated with developmental delays of cognitive and motor skills
Iron deficient children tend to be pale, weak, eat less, tire easily, be more irritable, have shorter attention spans, fall ill more frequently, and fail to grow normally

Copper
is integral part of enzyme lysyloxidase catalyzes formation of stable collagen cross-links Some cuproenzymes paly important role in oxidation

reduction reaction:

Role of copper-binding proteins in humans

 Dietary copper bioavailability (40 to 60%) can be

affected by
other nutrients status of ceruloplasmin.

Copper stores (+ 120 mg) are mainly in liver are secreted in saliva, gastric & pancreatic juice & bile Coppermetallothionein complex present in intestinal

mucosal cells is shed into intestinal lumen.

Iodine
is important in cellular oxidative processes

associated with thyroid functions. Iodine deficiency:

causes endemic cretinism, associated with deaf

mutism & cerebral palsy.

Principal role of iodine in man is: its incorporation into thyroid hormones (T3 and T4):
regulate cellular metabolism, temperature, and normal growth.

+ 2/3 of total body iodine is found in thyroid.

Iodine deficiency
Iodine deficiency is the worlds most prevalent

cause of brain damage Serious iodine deficiency during pregnancy may result in stillbirths, abortions and cretinism
Yet, the less visible, more pervasive form of

iron deficiency that lowers intellectual performance at home and school may have far greater global and economic impact

Manganese
Mn-SOD and pyruvate carboxylase are two most

important metalloenzymes of manganese.

Play important role in homeostasis of metabolic

synthesis of:
proteins, (mucopolysaccharides & prothrombin) carbohydrate and lipid (e.g., activates lipoprotein lipase

activation, cholesterol, and sex hormone precursors

Stores are found in mitochondria of hepatic,

renal, pancreatitic, bone, and skeletal muscle parenchyma.

Manganese
Deficiencies have been manifested as:

tardive dyskinesia epilepsy diabetes mellitus pancreatic insufficiency malnutrition hair color changes hypercholesterolemia prolonged prothrombin times.

Magnesium (Mg)
is a macromineral that is essential for wound

repair
is a cofactor for many enzymes that are involved

in process of protein synthesis.

The primary role of magnesium is to provide

structural stability to ATP, which powers many of the processes used in collagen synthesis, making it a factor essential to wound repair

 Magnesium modulates cellular events involved in

inflammation.
Mg deficiency in rat induces a clinical

inflammatory syndrome characterized by

polymorphonuclear (PMN) leukocyte macrophage activation release of inflammatory cytokines and acute phase

proteins excessive production of free radicals.

Mg acts as a natural calcium antagonist

molecular basis for inflammatory response is probably result of modulation of intracellular calcium concentration

 Mg deficiency contributes to an exaggerated: response to immune stress hyperlipemia atherosclerosis endothelial dysfunction thrombosis hypertension free radical damage

 Assessment of magnesium status: urine magnesium concentration is the most precise When sufficient excretion is evident (i.e., greater than 50% of intake)

intracellular magnesium concentration is sufficient.

Magnesium and zinc: both essential for enzymatic activity maintaining three-dimensional structures of proteins synthesis of nucleic acids and proteins

Calcium:
Calcium and phosphorus serve as structural components

of bones and teeth

Calcium (Ca2) plays many other roles in the body: is involved in hormone action and blood clotting Calcium ions mediate: attaching blood clotting proteins to a surface by
binding to two negatively charged carboxyl groups of glutamate two additional negatively charged groups provided by

phospholipids in cell membrane.

Calcium:
Ca2-calmodulin is modulator protein that binds to

a number of different proteins and regulates their function

One of the enzymes activated by Ca2-calmodulin

is muscle glycogen phosphorylase kinase

Calcium binding to troponin prepares the muscle

for contraction.
The Ca2-ATPase, a calcium pump, maintain

intracellular Ca2 concentration below 107 M.

Calcium:
High levels of intracellular Ca2 are associated

with irreversible progression from cell injury to cell death.

A dietary deficiency of calcium can lead to

osteoporosis, a disease in which bones are insufficiently mineralized and consequently are fragile and easily fractured.
Osteoporosis is a particularly common problem

among elderly women.

Phosphorus
Phosphorus is required for the formation of

ATP and of phosphorylated intermediates in metabolism.

Deficiency of phosphorus results in bone loss

along with weakness, anorexia, malaise, and pain.

Deficiency of phosphorus results in bone loss

along with weakness, anorexia, malaise, and pain.