MINERALS AND HOMEOSTASIS

Harliansyah, Ph.D
Composition of the Human
Body

Figure 27–1b
 Body Fluid
• to maintain good health, a balance of fluids and electrolytes,
acids and bases must be normally regulated for metabolic
processes to be in working state.

• A cell together with its environment in any part of the body,

is primarily composed of FLUID.

• Body Fluids Function:

1. transporter of nutrients, wastes, hormones, etc
2. medium for metabolic processes
3. body temperature regulation
4. lubricant of musculoskeletal joints
5. insulator and shock absorber
 Fluid Compartments
• Water (60% of Body Weight) occupies two main fluid
compartments
• Intracellular fluid (ICF) – about two thirds by volume,
contained in cells ≈ 40% (28 L)
• Extracellular fluid (ECF) – consists of two major
subdivisions ≈ 20%(14 L)
– Plasma – the fluid portion of the blood ≈ ¼ (3 L)
– Interstitial fluid (IF) – fluid in spaces between cells ≈ ¾
(11 L)
• Other ECF – lymph, cerebrospinal fluid, eye humors,
synovial fluid, serous fluid, and gastrointestinal
secretions
 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
proteins

Transferrin – Fe, Cr, Mn, Zn

Albumin – Cu, Zn
Amino acids – Cu, (Fe)
Trancobaltamin - Co
Globulins - Mn
Normal routes of excretion of trace
elements

Bile – Cu, Mn, Cr, Zn,

Urine – Co, Cr, Mo, Zn
Pancreatic juice – Zn
Sweat – Zn
Mucosal cell sloughing – Fe, Zn
 Homeostasis
• Keadaan homeostasis atau steady state
– homoios (sama), stasis, (menetap)  “tetap sama”
– “keadaan yang bisa berubah, secara relatif konstan”
• Walter B. Cannon
– bukan sesuatu yang tidak pernah berubah,
– tidak selalu sama sepanjang waktu.
• Sel: untuk survive dalam kondisi sehat
– seluruh aspek lingkungan harus relatif konstan: komposisi kimia,
tekanan osmosis, [H+], suhu, dsb.
– perubahan kecil  fungsi sel tidak optimal
– perubahan besar  sel dan tubuh mati
 Lingkungan kehidupan sel
• Tidak sama dengan lingkungan kehidupan tubuh.
– tubuh di dalam atmosfir; udara luar = lingkungan luar
– sel di dalam cairan interstitium = lingkungan dalam
• Cairan ekstrasel (di luar sel) berada di
– intersel/interstisium, mengisi ruangan di antara sel
– plasma, mengalir di pembuluh darah.
• Claude Bernard, Perancis: “milieu interne”
– cairan ekstrasel lingkungan kehidupan sel
– komposisi fisika/kimia harus dipertahankan konstan
• Walter B. Cannon, Amerika
– menamakan kekonstanan relatif ‘lingkungan dalam’
– sebagai homeostasis.
 Mempertahankan homeostasis
• Merupakan tema utama Fisiologi.
– melibatkan proses-proses mekanisme homeostasis
– pelaksanaan fungsi semua organ dan sistem tubuh
• Illustrasi mengenai proses homeostasis
– kolam renang, tinggi permukaan 150-155 cm
sebagai bentuk homeostasis air
– kalau terjadi sumbatan pada pipa masuk
volume air berkurang, ketinggian akan < 150 cm.
– mekanisme homeostatis bekerja
sensor otomatis mengaktifkan alat lain
mengurangi aliran pada pipa keluar,
ketinggian air kembali ke tingkat homeostasis
Dasar mekanisme homeostasis
• Perubahan lingkungan internal merangsang sensor
– mengaktifkan respons pengembalian homeostasis.
– membalikkan perubahan ke homeostasis.
• Respons pembentuk mekanisme homeostasis
– disebut sebagai respons adaptif (penyesuaian).
– penyesuaian tubuh dengan perubahan lingkungan
– perubahan tubuh akibat perubahan lingkungan
dan perubahan lingkungan akibat perubahan tubuh.
• Adaptasi: penggabungan organisme - lingkungan
– kalau berhasil: survival yang sehat
– kalau gagal: penyakit atau kematian.
 Generalisasi fungsi tubuh
• Kategori umum fungsi tubuh
– fungsi survival (daya bertahan hidup),
– fungsi homeostasis lingkungan dalam,
– aktifitas terus menerus,
– memiliki fungsi-fungsi organ,
– berubah sesuai dengan perjalanan waktu.
• Survival (daya bertahan hidup)
– urusan tubuh yang paling utama,
– mencakup survival tubuh dan survival makhluk
– tergantung pada kemampuan tubuh menjaga atau
mengembalikan homeostatis lingkungan internal.
• Homeostasis tergantung kemampuan
melaksanakan berbagai aktifitas terus-menerus
• Fungsi utama
– berespons terhadap perubahan lingkungan,
– pertukaran zat antara lingkungan dan sel
– metabolisme makanan, dan
– integrasi aktifitas yang sangat beragam.
• Fungsi-fungsi tubuh pada dasarnya adalah fungsi
sel-selnya.
 Process that occurs in
all living things
 All organ systems work
together to achieve
homeostasis  Body Temperature
 Ability of an organism to  Blood pressure
maintain its internal  Blood pH
environment, despite
changes to its internal or  O2 and CO2
external environment concentration
 Osmoregulation-
Water balance
 Blood glucose
Homeostasis Radikal Bebas
Metabolic Homeostasis
 Kemampuan melaksanakan
fungsi
• Berubah perlahan
– kurang mampu: di 2 ujung kehidupan, bayi/tua.
– kanak-kanak: fungsi lebih efisien/efektif.
– remaja: tingkat efisiensi/keefektifan maksimum.
– menjelang tua: kurang efisien/efektif.
• Perubahan fungsi
– di awal kehidupan  proses perkembangan,
dan pada usia senja  disebut proses penuaan.
– perkembangan  kapasitas makin baik,
proses penuaan  mengurangi kapasitas
 Lingkungan dalam
• Cairan antar sel: tempat sel hidup
– lingkungan dalam: millieu interieur
– adalah lingkungan ‘luar’ untuk sel
– disebut cairan interstitium (CI)
• Jarak terjauh sel dan kapiler 50 
– plasma, makanan, dan O2 masuk ke CI
– CI, sisa metabolisme dan CO2 ke kapiler
– CI dan protein masuk ke pembuluh limfe
 Cairan : 60% tubuh dewasa
• Ekstrasel 33%, intrasel 67%
• Cairan ekstrasel: di luar sel
– Cairan darah: selalu bergerak cepat
• curah jantung: 70 ml/denyut x 72 denyut/menit
• volume darah: sekitar 5000 ml
– Cairan interstitium:
• di antara sel-sel, ‘millieu interieur’
• sumber kehidupan sel
– Lain: cairan sendi, otak, pleura, dsb.
Cations
Body
Fluids

Figure 27–2 (1 of 2)
Anions in
Body
Fluids

Figure 27–2 (2 of 2)
 Sodium
• 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
balance.
• 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
 Sodium
•Hypernatremia is associated with water depletion
(dehydratation).
• Low serum Na+ - hyponatremia, is associated with
excess of intravascular (and perhaps extravascular)
water.
• 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
 Potassium

• 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
contraction
• The main dietary source is the cellular material we
consume as foodstuffs.
 Potassium

• 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
Na-K-ATPase.
• Acidosis (pH < 7,36) causes hyperkalemia → transient
shifting of K+ from cells at the expense of H+
• Hyperkalemia produces characteristic electrocardio-
graphic changes (life-threatening effect of K+ excess on
the heart).
 Calcium
• Total content of calcium in the body is more than 1200
mg.
• 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
Secretion
Biomineralization
 Calcium metabolism
• Absorption – duodenum and proximal jejunum.
• Active transport across cells.
• Calcium-binding proteins (calbindins) are synthesized
in response to the action of 1,25-
dihydroxycholecalciferol (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,
soyabeans),
phosphates (formation of insoluble salts),
sodium,
caffein
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
disoders.
Result of vit. D deficiency, hypoparathyroidism, renal
insuficiency.
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
nucleotides
phospholipides
phosphoproteins
Enzymes that attach phosphates in ester or acid anhydride
linkages
Other enzymes (phosphatases, pyrophosphatases)
Blood phosphate: H2PO4- and HPO42-
Concentration 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 1,25-
dihydroxycholecalciferol and parathyroid hormone.

PTH mediates mobilization and deposition of calcium and phosphate

from bone.

Deficiency
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.

 Magnesium
• 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
2+

reactions utilizing ATP and other nucleotide triphosphates as

substrate.
• 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
molecule.
• 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
mmol/l).

• Total cellular concentration can

vary from 5 to 20 mmol/l.

• Intracellular Mg2+ is
predominantly complexed to organic
molecules.
 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
(tetany).

Excess of Mg2+ cause vasodilatation.

 Magnesium metabolism

Hypomagnesemia cause:

• changes in skeletal and cardiac muscle

• changes in neuromuscular function,
• hyperirritability, psychotic behaviour
• tetany

Hypermagnesemia cause:

• muscle weakness
• hypotension
• ECG changes
• sedation and confusion

Hypermagnesemia is usual due to renal insuficiency.

 Copper
• 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
mechanism.
 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)
tyrosinase
monoamino oxidase
lysyloxidase

• Cu metabolism is altered in inflammation, infection, an

cancer.
• In infection, Cu is essential for production of Ile-2 by
activated lymphocytes.
• In cancer, plasma CP is positively correlated with
disease stage.
 Iron
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
molecules.

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.
 Molybdenum
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
utilization.
(the foot content of Mo is highly dependent upon the
soil type in which the foodstuff are grown).
 Selenium
• an integral component of glutathion peroxidase
(intracellular antioxidant),
• a scavenger of peroxides,
• an essential element for immune function
(selenoproteins).

• Selenoproteins catalyse oxido-reduction reactions,

protective function from oxidative stress (macrophage-
or neutrophil-generated free-radical species, UV in
sunlight.

The foot content of Se is highly dependent upon the soil

type in which the foodstuff are grown.
 Manganese
• 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,
proteoglycans.
• Required for superoxid dismutase activity, for
activity of metalloenzymes:
hydrolases
kinases
decarboxylases
transferases.

Deficiency of Mn extensively reduce glycoprotein and

proteoglycan formation.
 Zinc

Component of zinc metalloenzymes :

carbonic anhydrase
lactate dehydrogenase
glutamate dehydrogenase
alkaline phosphatase
thimidine kinase
matrix metalloproteinases

Gustin – protein in saliva – major role in taste.

 Zinc

Deficiency of Zn has serious consequence :

• failure metabolism of nucleic acids (cell division, growth and

differentiation)
• multisystem disfunction as growth retardation,
hypogonadism, ophtalmologic, gastrointestinal,
neuropsychiatric symptoms.

Zink deficiency in children are marked by poor growth and

impairment of sexual development.
 Chromium
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
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.
 Fluorine
Inorganic matrix of bone and teeth.
Deficiency – osteoporosis and teeth caries.

Boron
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).
 Vanadium
Control of sodium pump, inhibition of ATPase

Tin
Interaction with riboflavin

Lithium
Control of sodium pump, interference with the lipid metabolism

Silicon
Structural role in connective tissue, in metabolism of osteogenic cells

Nickel
Component of enzyme urease
 anabolic steroid,
estrogen
K+ Irregular heart rythm, Hemolysis, Action potentials, nerve
muscle weakness, Diarrhea, polarization/ depolarized
paralysis Dehydration,
weakness.
Ca2+ Decreased (PTH, Vit Hyperthyroid , Neuromuscular cell
D), Acute inflammation Vomiting, Anorexia activity
of the pancreas.
Tetany
Mg2+ Neuromuscular Diarrhea, nausea, Bound to ATP
weakness, Irritability, mental status
Convulsion, Tetany change, appetite
loss.
Cl- Hyperexcitability of the Lethargy, The level of Cl- usually
muscle, nerves. weakness, deep follows the Na+ level,
Hypotension (Low breathing except in cases of acid-
blood pressure), base imbalance.
Tetany
HPO4 Poor absorption, Acromegaly, cell Evaluated PTH or
weakness of injury, tumor. Calcium
respiratory
muscle.delirium
Electrolyte Regulation
Ion Mechanism
Na+ Aldosterone, Antidiuretic Renal
hormone (ADH) reabsorption,
Renal excretion
K+ Intestinal absorption Glucocorticoids Renal
reabsorption,
Renal excretion

Ca2+ Parathyroid hormone Calcitonin, Renal

intestinal reabsorption,
absorption Renal excretion

Mg2+ Intestinal absorption Renal Renal excretion

reabsorption
Cl- Intestinal absorption Renal Renal excretion
reabsorption

HPO4 Component of bone Synthesis DNA, Generation of ATP

RNA
Terima Kasih