Jana Novotná
1. Major components of body molecules
C, H, O, N, S
(obtained through intake of water fat, carbohydrates, proteins)
2. Nutritionally important minerals
Ca, P, Mg, Na K, Cl
(<100 mg/day)
3. Trace elements
Cr, Co, Cu, I, F, Fe, Mn, Mo, Se, Zn
4. Additional elements (non-essential for humans)
Ni, Si, Sn, V, B, Li
Transport and storage require
specific binding to carrier
Transferrin – Fe, Cr, Mn, Zn
Albumin – Cu, Zn
Amino acids – Cu, (Fe)
Trancobaltamin - Co
Globulins - Mn
Normal routes of excretion of trace
Bile – Cu, Mn, Cr, Zn,
Urine – Co, Cr, Mo, Zn
Pancreatic juice – Zn
Sweat – Zn
Mucosal cell sloughing – Fe, Zn
Na+ is the major cation of extracellular fluid.
Plasma concentration - 135 -145 mmol/L
ICT concentration - 3-10 mmol/L.
Maintaining of total body fluid homeostasis and water
• Decrease in blood pressure and decreases in sodium
concentration result in the production of renin →
aldosteron production → decreases the excretion of
sodium in the urine
•Hypernatremia is associated with water depletion
• Low serum Na+ - hyponatremia, is associated with
excess of intravascular (and perhaps extravascular)
• Maintaining electric potential in animal tissues
• Na+ are important in neuron (brain and nerve)
function – action potential
• Na+ are important in maintaining and influencing
osmotic balance between cells and the interstitial fluid
• Distribution is mediated by the Na+/K+-ATPase pump
K+ is the principal cation of the intracellular fluid.
Plasma concentration - 3,5 - 5,2 mmol/L.
ICF concentration - 110 -160 mmol/L.
Key role of K+ in skeletal and smooth muscle
• The main dietary source is the cellular material we
consume as foodstuffs.
• The concentration of K+ in plasma is influenced by the
pH of the blood (physiological pH 7,4 ± 0,04).
• Alkalosis (pH > 7.44) causes hypokalemia → transient
shifting of K+ into cells, presumably by stimulation of the
• Acidosis (pH < 7,36) causes hyperkalemia → transient
shifting of K+ from cells at the expense of H+
• Hyperkalemia produces characteristic electrocardiographic changes (life-threatening effect of K+ excess on
the heart).
Total content of calcium in the body is more than 1200
• 99% of total content is deposit in bones and teeth,
• 1% in blood and body fluids
• Intracellular calcium:
- cytosol
- mitochondria
- other microsomes
- regulated by "pumps"
The serum level of calcium is closely regulated with a normal
total calcium of 2 -2.75 mmol/L (9-10.5 mg/dL) and a normal
ionized calcium of 1.1-1.4 mmol/L (4.5-5.6 mg/dL).
Calcium metabolism
Multiple biological functions of calcium
Cell signaling
Neural transmission
Muscle function
Blood coagulation
Enzymatic co-factor
Membrane and cytoskeletal functions
Calcium metabolism
• Absorption – duodenum and proximal jejunum.
• Active transport across cells.
• Calcium-binding proteins (calbindins) are synthesized
in response to the action of 1,25dihydroxycholecalciferol (vitamin D3).
• Parathyroid hormone – also increased intestinal
absorption of Ca.
Calcium metabolism
Absorption is inhibited by:
oxalates (salts of oxalic acid),
phytates (salts of phytic acid - found in grain,
phosphates (formation of insoluble salts),
Recommended daily amount:
Children to age 11 – 1200 mg/day
From age 11 to 24 – 800 mg/day
From age 24 – 500 mg/day
In woman after menopase – 1500 mg/day (osteoporosis prevention).
Deficiency - hypocalcemia
tetany, increased neuromuscular excitability, neurological
Result of vit. D deficiency, hypoparathyroidism, renal
Symptoms are: rickets (children), osteomatacia (adults)
Toxicity – hypercalcemia (normally does not to occur)
Hyperparathyroidism, vitamin D intoxication, cancer.
Phosphorus metabolism
Major role in structure and function of all living cells and as a
free ion
Integral part of:
nucleic acids
Enzymes that attach phosphates in ester or acid anhydride
Other enzymes (phosphatases, pyrophosphatases)
Blood phosphate: H2PO4- and HPO42Concentration measured as phosphorus: 2.5 - 4.5 mg/100 ml
Skeletal hydroxyapatite - Ca(PO4)2 or Ca(OH)2
Phosphorus metabolism
Absorption in the jejunum.
Phosphate absorption is regulate by 1,25dihydroxycholecalciferol and parathyroid hormone.
PTH mediates mobilization and deposition of calcium and phosphate
from bone.
Rickets in children, osteomalacia in adults.
Abnormalities in erythrocytes, leucocytes, platelets, liver.
Depletion of phosphate occurs as a result of diminished absorption
from intestine or excessive wasting through kidney.
Hyperphosphatemia is associated with renal diseases.
• Nearly 99% of the total body magnesium is located in bone or the
intracellular space.
• Second plentiful cation of the extracellular fluids.
• Mg is a cofactor of all enzymes involved in phosphate transfer
reactions utilizing ATP and other nucleotide triphosphates as
Required for the structural integrity of numerous intracellular
proteins and nucleic acids.
A substrate or cofactor for important enzymes such as adenosine
triphosphatase, guanosine triphosphatase, phospholipase C,
adenylate cyclase, and guanylate cyclase.
A required cofactor for the activity of over 300 other enzymes.
A regulator of ion channels; an important intracellular signaling
A modulator of oxidative phosphorylation.
Mg2+ is chelated between the beta and gamma
phosphates, diminishes the dense anionic
character of ATP
Magnesium metabolism
Only 1% to 3% of total
intracellular Mg2+ exist as a free
ionized form (conc. 0.5 to 1.0
Total cellular concentration can
vary from 5 to 20 mmol/l.
Intracellular Mg2+ is
predominantly complexed to organic
Magnesium metabolism
Effect on central nervous system:
Certain effects of Mg2+ are similar to Ca2+.
Increased concentration of Mg2+ cause depression of CNS
Decreased concentration of Mg2+ cause irritability of CNS
Effect on neuromuscular system:
Direct depressant effect on skeletal muscles – excess of Mg2+
cause decrease in acetylcholine release by motor nerve impulse.
• The action of increased Mg2+ on neuromuscular function are
antagonized by Ca2+.
• Abnormaly low concentration of Mg2+ in extracellular fluid result in
increased acetylcholine release and increased muscle excitability
Excess of Mg2+ cause vasodilatation.
Magnesium metabolism
Hypomagnesemia cause:
changes in skeletal and cardiac muscle
changes in neuromuscular function,
hyperirritability, psychotic behaviour
Hypermagnesemia cause:
muscle weakness
ECG changes
sedation and confusion
Hypermagnesemia is usual due to renal insuficiency.
• Cu is an essential nutrient.
• Rapid growth increases Cu demands in infancy.
• The adult body contains approximately 100 mg of copper
– the highest concentrations are in liver, kidney, and hearth.
• The absorption in gastrointestinal tract requires a specific
mechanism - metal binding protein
metallothionein (Cu2+ ions are highly insoluble).
• Ceruloplasmin (CP) is a glycoprotein, copper-dependent
ferroxidase (95% of the total copper in human plasma),
oxidizes Fe2+ to Fe3+ in gastrointestinal iron absorption
Copper metabolism
Model of Cu uptake and metabolism in hepatocytes:
Cu cross the plasma membrane through Ctrl1 (copper transporter1) or DMT1
(divalent metal transporter1) to the trans Golgi network (TGN) by chaperone Hah1.
Chaperone protein Ccs delivers Cu to cytosolic Cu/Zn SOD. Cox17 delivers Cu to
mitochondria for cytochrome c oxidase.
Carrol et all, 2004)
Copper metabolism
Cu is an essential cofactor in a number of critical
enzymes in metabolism:
superoxide dismutase (Cu/Zn-SOD)
cytochrome c oxidase (COX)
monoamino oxidase
Cu metabolism is altered in inflammation, infection, an
• In infection, Cu is essential for production of Ile-2 by
activated lymphocytes.
• In cancer, plasma CP is positively correlated with
disease stage.
Major function of Fe – oxygen transport by hemoglobin.
Fe2+ and Fe3+ are highly insoluble – special transporter
systems are required.
Food Fe is predominantly in Fe3+, tightly bound to organic
Apoferritin assimilates up to 4 300 Fe molecules to form
Fe storage protein – ferritin.
In the retikuloendothelial system ferritin provides an
available storage form for iron.
Apotransferrin (apoTf) – protein, that can bind 2 atoms
of Fe to form transferrin, Fe carrier in plasma.
Food iron is predominantly in the ferric state.
In the stomach, where the pH is less than 4, Fe3+
can dissociate and react with low-molecular weight
compounds such fructose, ascorbic acid, citric acid,
amino acids to form ferric complexes soluble in
neutral pH of intestine fluid.
A protein DMT1 (divalent metal transporter 1),
which transports all kinds of divalent metals, then
transports the iron across the cell membrane of
intestinal cells. These intestinal lining cells can
then store the iron as ferritin.
The transfer of iron from the storage ferritin (as
Fe3+ ) involves reduction to ferrous state – Fe2+ in
order for it to be released from ferritine.
The Fe2+ is subsequently again oxidized by
ferroxidase ceruloplasmin and transported bound to
plasma transferrin to storage sites in the bone
marrow, liver muscle, other tissues.
Metal required for the function of the metalloenzymes:
xantine oxydase
aldehyde oxidase
sulfite oxidase
Some evidence that Mo can interfere with Co
metabolism by the diminishing the efficiency of copper
(the foot content of Mo is highly dependent upon the
soil type in which the foodstuff are grown).
an integral component of glutathion peroxidase
(intracellular antioxidant),
• a scavenger of peroxides,
• an essential element for immune function
Selenoproteins catalyse oxido-reduction reactions,
protective function from oxidative stress (macrophageor neutrophil-generated free-radical species, UV in
The foot content of Se is highly dependent upon the soil
type in which the foodstuff are grown.
High concentration of Mn2+ is present in mitochondria
Functions as a necessary factor for activation of
glycosyltransferases (enzymes responsible for the
synthesis of oligosaccharides, glycoproteins,
• Required for superoxid dismutase activity, for
activity of metalloenzymes:
Deficiency of Mn extensively reduce glycoprotein and
proteoglycan formation.
Component of zinc metalloenzymes :
carbonic anhydrase
lactate dehydrogenase
glutamate dehydrogenase
alkaline phosphatase
thimidine kinase
matrix metalloproteinases
Gustin – protein in saliva – major role in taste.
Deficiency of Zn has serious consequence :
• failure metabolism of nucleic acids (cell division, growth and
• multisystem disfunction as growth retardation,
hypogonadism, ophtalmologic, gastrointestinal,
neuropsychiatric symptoms.
Zink deficiency in children are marked by poor growth and
impairment of sexual development.
Regulation of glucose metabolism as a component of
glucose tolerance factor (GTF).
GTF increases effect of insulin (by facilitating its binding to
cell receptor site).
Chromium regulates plasma lipoprotein concentration.
Reduces serum cholesterol and serum triglycerides.
Iodine is incorporated into thyroid hormones.
Iodine is absorbed in the form of inorganic iodine.
Thyreoperoxidase oxidizes inorganic iodine and oxidized I is
transported to phenyl group of tyrosin of thyroglobulin.
Inorganic matrix of bone and teeth.
Deficiency – osteoporosis and teeth caries.
Influences of metabolism and use of Ca, Cu, Mn, N,
glucose, triglycerides.
Control of membranes function and their stabilization.
Negative influence on many metabolic processes –
inhibition of some key enzymes (inhibition of energetic
metabolism), immune system (respiratory burst).
Control of sodium pump, inhibition of ATPase
Interaction with riboflavin
Control of sodium pump, interference with the lipid metabolism
Structural role in connective tissue, in metabolism of osteogenic cells
Component of enzyme urease