BIOKIMIA MINERAL

Calsium
Phosphor
Iron
Zinc
Iodine

Dr Nur Rahman, STP MP

 CALCIUM
 Jumlah mineral paling banyak dlm tubuh
sekitar 1.5%-2% berat bb dan 39% of total
minerals tubuh.
 99% calcium ada di bone and teeth
 1% of calcium is in the blood and extracellular
fluids and within the cells of all tissues, yg
berfungsi mengatur metabolisme.
 Calcium occurrence
In nature
 Tidak ada yg bebas
 Occurs mostly in soil systems as limestone
(CaCO3), gypsum (CaSO4*2H2O) & fluorite (CaF2)
In the body
 The most abundant mineral
 Average adult body contains app. 1 kg
 0,1 % in the extra cellular fluid
 1 % in the cells
 The rest (app. 99 %) in the skeleton
(Bones can serve as large reservoirs, releasing calcium when
extracellular fluid concentration decreases and storing excess
calcium)
 Calcium functions
 Elemen penyususn utama tulang dan
gigi calcium phosphate
(Ca10(PO4)6(OH)2 (hydroxyapatatite)
 Komponen struktur sel
 Kekuatan tulan tgt dari konsentrasi l
calcium
 Hormone regulation of
calcium-phosphorus metabolism
Parathyroid hormone Vitamin D Thyreocalcitonin
(PTH)
Organ-target: bones, kidneys Organ-target - bones

Function of PTH - increase of Ca

concentration in plasma Function - decrease of Ca
concentration in plasma
Mechanisms:
1. Releasing of Са by bones
(activation of osteoclasts –
resumption of bones)
2. Increase of Са reabsorbing in
kidneys
3. Activation of vit. Dз synthesis
and increase of absorption
in the intestine
 Pathways of Calsium
Metabolism
Pengaturan metabolism
Calsium melibatkan :
intestinal absorption (gut),
blood calsium (Ca) and
Phosphate (P) concentrations,
bone,
the kidneys-which produce the
hormonal form of vit D-and
parathyroid glands (PTG),
mengeluarkan parathyroid
hormone (PTH).
Rendah serum calsium or
high serum phosphate level
stimulates pengeluaran PTH n
(Step 1) through negative
 Calcium functions (Bone)
 Osteoclasts (bone cells)
remodel the bone by
dissolving or resorbing
bone
 Osteoblasts (bone
forming cells) synthesize
new bone to replace the
resorbed bone
- Found on the outer
surfaces of the bones
and in the bone cavities
 Calcium functions
Berperan penting dlm pengaturan tbuh .
A passive role:
- As a cofactor beberapa enzymes (e.g. Lipase) and proteins
- As component dlm pembekuan blood
An active role: as an intracellular signal
- In the relaxation and constriction of blood vessels
- In cell aggregation and movement
- In muscle protein degradation
- In secretion of hormones as insulin
- In cell division
- In nerve impulse transmission
 Absorption, Transport, Storage,
and Excretion

 Calsium diabsorsi di semua bagian

 small intestine, paling cepat di bagian
duodenum, dlm kondisi acidic medium
(pH < 7) prevails
 Calsium is absorbed by two mechanisms :
1. Active Transport
 Konsentrasi calcium di usus rendah
 Mainly in duodenum and proximal jejenum
 Has limited capacity, and it is controlled
through the action of Vit D
2. Passive transfer
 Konsentrasi calcium di usus rendah
 Independent of vit D
 Sepanjang usus halus
 Calcium dapat juga diabsorsi dicolon tapi
dlm jumlah kecil .
 Calcium diabsorsi dlm bentuk ion
 Calcium tidak dapat diabsorsi jikan ada
oxalate or if it forms soap with free fatty
acids. Calsium yg tidak diabsorb di
buang via feces as calcium oxalates and
calcium soaps
 Konsentrasi serum ionized calcium di
controlled primarily by PTH, hormone ini
dikeluarkan oleh parathyroid glands.
Dan hormon lainya calcitonin, Vit D,
estrogens and other.
 REGULATION OF SERUM
CALCIUM
 Calcium di tulang akan selalu menyeimbangkan
dg calsium dlm darah. PTH mengatur ca
serum selalu normal , yaitu 10 mg/100 ml of
blood serum (2,5 mmol/L).
 Ketika ca serum darah rendah , PTH stimulates
ca tulang ke darah.
 Dalam waktu yang sama PTH promotes renal
tubular resorption of calcium, and it indirectly
stimulates increased intestinal absorption of
calcium via the hormonal form of vitamin D
(1,25[OH]2D3)
 REGULATION OF SERUM
CALCIUM (lanjutan)
 Hormon yang lain spt : glucocorticoids,
thyroid hormones, and sex hormones juga
berperanan dlm calcium homeostatis
 Glucocorticoids berfungsi calcium absorption
secara active and passive mechanism
 Thyroid hormones (T4 and T3) stimulates
resorption bone; conditions chronic
hyperthyroid result in loss of compact and
trabecular bone.
REGULATION OF SERUM
CALCIUM (lanjutan)
 In woman, normal bone balance memerlukan
serum konsentrasi estrogen agar kondisi
normal .
 Kecepatan penurunan serum estrogen
concentration selama menopause
merupakan faktor contributing to bone
resorption. Treating postmenopausal women
with estrogen slows the rate of bone
resorption. Bone resorption dihambat by
testosterone.
 Interactions
 Phosphate: ↓ calcium excretion in the urine
 Caffeine: ↑ urinary and fecal excretion of calcium
 Sodium: ↑ sodium intake, ↑ loss of calcium in urine
 Dietary constituents: Phytic acid can reduce
absorption of calcium by forming an insoluble salt
(calcium phytate)
 Iron: calcium might have inhibitory effect on iron
absorption
 Absorption and excretion
 Usual intakes is 1000 mg/day
 About 35 % is absorbed (350 mg/day)
by the intestines
 Calcium remaining in the intestine is
excreted in the feces
 250 mg/day enters intestine via secreted
gastrointestinal juices and sloughed
mucosal cells
 90 % (900 mg/day) of the daily intake is
excreted in the feces
 10 % (100 mg/day) of the ingested
calcium is excreted in the urine
 Calcium must be in a soluble and
ionized form before it can be absorbed
 Absorption and excretion
factors
 Absorption increased by:  Excretion increased by:
- Body need - Low parathyroid hormone (PTH)
- Vitamin D - High extracellular fluid volume
- Protein - High blood pressure
- Lactose - Low plasma phosphate
- Acid medium - Metabolic alkalosis
 Absorption decreased by:  Excretion decreased by:
- Vitamin D deficiency - High parathyroid hormone
- Calcium-phosphorus imbalance - Low extracellular fluid volume
- Oxalic acid - Low blood pressure
- Phosphorous - High plasma phosphate
- Dietary fiber - Metabolic acidosis
- Excessive fat - Vitamin D3
- High alkalinity
- Also stresses and lack of exercise
 Metabolism

 Factors involved in calcium metabolism

Bone Growth and Calcium
Metabolism

Figure 23-19: Bone growth at the epiphyseal plate

Calcium Metabolism:

Figure 23-20: Calcium balance in the body

 Regulation
Vitamin D, parathyroid hormone and calcitonin
 Vitamin D (in active form)
- Berefek pada peningkatan absorbsi ca dan phospat pd intestine
and kidneys ke dlm cairan extracellular.
- Sangat berefek pd bone deposition and bone absorption
 Parathyroid hormone (PTH)
- Meningkatkan mechanism controlling extracellular calcium and
phosphate concentrations dg cara mengatur reabsorbsi di intestinal
, renal excretion and perubahan diantara cairan extracellular and
bone dari dua ions
 Calcitonin (a peptide hormone secreted by the thyroid gland)
- Cenderung decrease concentration plasma calcium
- In general, mempunyai efek yg berlawanan thd PTH.
 Regulation

Activation of vitamin D3
- Cholecalciferol formed in the
skin by sun
- Converted in liver
(feedback effect)
- 1,25 DHCC formation in kidney
- Controlled by PTH
- Plasma calcium
concentration inversely
regulates 1,25 DHCC
 Regulation

 Kondisi jika konsentrasi plasma ionized calcium menurun akan

dimediasi oleh PTH & vitamin D
 PTH regulates through 3 main effects:
- By stimulating bone resorption
- By stimulating activation of vitamin D → ↑ intestinal Ca reabsorption
- By directly increasing renal tubular calcium reabsorption
 Calcium and the Cell

 Translocation across the plasma membrane

 Translocation across the ER and mitochondrion;
Ca2+ ATPase in ER and plasma membrane
 Phosphor
 700 g phosphorus ada pd jaringan, dan
85% ada pd skeleton and teeth dlm
bentuk calcium phosphate crystals.
 The serum inorganic phosphorus diatur
PTH at 3 to 4 mg/100 ml in adults
Figure 5-3 Phosphorus Balance is maintained primarily by
the amount of phosphate absorbed versus the amount
excreted by the kidneys and intestine
 Absorption, Transport, Storage,
and Excretion
 Semua Phosphates di absorbed dlm
bentuk inorganic state
 Ikatan Organically phosphate dihidrolisis
di lumen intestine dan selanjutnya di
keluarkan sbg inorganic phosphate,
primarily through the action of pancreatic
or intestinal phosphatases
 Bioavailability tgt bentuk dan pH
phosphate.
 Adanya senyawa pitat akan
pengaruhi phosphorus .
 The efficiency of phosphate absorption is
60% to 70% in adults, almost twice as
high as for calcium
 The primary route of phosphorus
excretion is renal, which also the primary
site of phosphate regulation
 Hal utama penyebab hilangnya phosphorus
dalam urin :
1. An increased intake of phosphate
2. An increase in phosphate absorption
3. The plasma Phosphorus concentration
4. Hyperparathyroidism
5. Acute respiratory or metabolic acidosis
6. The intake of diuretics
7. The expansion of extracellular volume
 Jika PTH levels tinggi, pengeluaran pospat
akan meningkat.
 Kekuranga gizi dapat menyebabkan 
hypophosphatemia dan renal losses of
phosphate
 Penurunan eksresi pospat berhubungan
dg :
 Pembatasan dietary phosphorus;
 Peningkatan plasma insulin, thyroid hormone,
growth hormone, glucagon, or glucocorticoids;
 metabolic or respiratory alkalosis; and
 extracellular volume contraction
 Toxicity
 Konsentrasi PTH yg tinggi secara permanen
akan disebabkan konsemsi low-calcium, high-
phosphorus diet  “Nutritional Secondary
Hyper-parathyroidism”
 Selain itu akan terjadi peningkatan bone
turnover that potentially can result in a reduction
of bone mass and density
 Adequate calcium intakes, yg berasal dari
suplemen akan menurunkan serum PTH
concentration and membantu menghambat bone
loss
 MAGNESIUM
 Magnesium jumlah terbanyak kedua
setelh Potassium) dlm intracellular cation.
 In adult : approx. 20-28 g of magnesium,
of which approx 60% is found in bone,
26% in muscle, and the remainder in soft
tissues and body fluids.
 Magnesium in bone is present in
exchangeable and non-exchangeable
pools
 Normal serum levels 1,5 to 2,1 mEq/L
(0,75 to 1,1 mmol/L)
 ½ magnesium in plasma is free, approx
1/3 is bound to albumin, and lainnya
complexed with citrate, phosphate, or
other anions
 No hormone yang terkait dg serum
magnesium, although PTH has a minor
role
Absorption, Transport, Storage,
and Excretion
 Efficiency absorption magnesium : 35% -
45%
 Mg diabsorbsi sepanjang small intestine, but
lebih banyak di jejunum
 Mg masuk dari saluran usus melalui 2
mekanism :
1. a carrier-facilitated process (at low intraluminal
conc)
2. simple diffusion (at high intraluminal conc)
Absorption, Transport, Storage,
and Excretion (lanjutan)
 efficiency absorption tgt dari : Mg status,
jumlah Mg diets, composition diet .
 Vit D has little or no effect on Mg absorption
 No homeostatic system for serum Mg
regulation has been identified, but the serum
Mg concentration is remarkably constant
 Maintenance of these constant values depend
on absorption, excretion, and
transmembranous cation flux rather than on
hormonal regulation
 Magnesium Balance

Figure 5-5 Magnesium Balance is maintained largely by GI

Absorption and Renal Excretion
 IRON
 Iron dalam tubuh ada dua pengepoolan: (1)
functional iron in hemoglobin, myoglobin, and
enzymes, and (2) storage iron in ferritin,
hemosiderin, and transferrin ( a transport protein
in blood)
 Iron is highly conserved by the body; approx
90% is recovered and reused every day. The
rest is excreted, primarily in the bile. Dietary iron
must be available to maintain iron balance to
meet this 10% gap, or else iron defficiency
results
Absorption, Transport, Storage,
and Excretion
 Dietary iron ada dua bentuk secara kimia
:
1. Heme iron, yg ditemukan dlm hemoglobin,
myoglobin, and some enzymes
2. Non-heme iron, yg ditemukan pd plant
foods tetapi juga ada beberpa di animal
foods, as are nonheme enzymes and ferritin
 Intestinal Absorption of Iron from heme
and Non-heme sources by an intestinal
absorbing cell, or enterocyte  see next
page
 Ada beberapa bentuk yg mengandung protein heme :
 Hemoglobin, myoglobin, enzim (Nitrite oxide synthase dan rpostaglandin sintase.
 Non heme :
 Besisulfur protein oxidative phosporilation, dan transpot dan penyimpanan protein
misalnya transferin, ferritin,
 Fe dikonsumsi dlm bentuk fe bebes atau fe heme.
 Dlm usus direduksi dari frri menjadi ferro dlm enterocite. Dan ditransport dg bantuan
DMT1 (divalent metal transporter.
 Sedangkan usus mengambil heme fe dg bantuan HCP1 heme carrier protein, heme
akan dilepas lagi menjadi fe dg bantuan enzim heme oxygenase .
 Iron dapat disimpan dlm usus enterocite atau ditranport ke darah .
 Besi ditranspor ke sirkulasi darah dg bantuan IREG1 (iron regulated gene 1). Dg
bantuan enzim hephastine akan mengoksidasi ferro menjadi ferri kembali.
 ZINC
 Banyak terdapat dlm bentuk zinc di animal
flesh, particularly red meat and poultry.
 Milk is a good source of zinc, but high
intakes of calcium from the milk
mengganggu absorption iron and zinc
 Tubuh mengandung 2 to 3 g of zinc, with
the highes concentrations in the liver,
pancreas, kidney, bone, and muscles
Absorption, Transport, Storage,
and Excretion
 Zinc absorption and excretion are
controlled dg mekenisme homeostatic yg
blm jelas
 The mechanism of absorption involves
two pathways similar to those of calcium
 The entry step of absorption across the
brush border is followed by the binding of
zinc ions to metallothionein and other
proteins within the cytosol of the
absorbing cell.
Absorption, Transport, Storage,
and Excretion
 Metallothionein carries the zinc (via
transcellular movement) to the
basolateral border for the exit step from
the absorbing cell to the blood.
 The exit step occurs by active transport
 Zinc absortion is affected tidak hanya
jumlah zinc dlm diet tetapi adanya
adanya zat pengganggu spt phytates
Absorption, Transport, Storage,
and Excretion
 A protein –rich diet membantu zinc absorption
dg membentuk ikatan zinc amino acid yg
mempermudah zinc diabsorbsi
 Absorption is associated with a variety of
intestinal deseases, such kekurangan
pancreatic
 Copper and cadmium compete for the same
carrier protein, so they reduce zinc absorption
 High intake of iron dpt menurunkan zinc
absorbed
 High Ca intakes menurunkan zinc absorption
and balance
IODIUM
Thyroid gland
Thyroid Gland: Hormones and
Iodine Metabolism

Figure 23-7b: The thyroid gland

Thyroid gland
Thyroxine and its precursors:
Structure & Synthesis

Figure 23-8: Thyroid hormones are made from tyrosine and iodine
Thyroxine and its precursors:
Structure & Synthesis

Figure 23-9: Thyroid hormone synthesis

Thyroid Follicles
Synthesis and Secretion of the Thyroid Metabolic Hormones

• Physiologic Anatomy of the Thyroid

Fig. 76.1
 Synthesis and Secretion of the Thyroid Metabolic Hormones

• Iodine is Required for the Formation of

• Thyroxine

a. Iodine dlm bentuk iodides ; 1.0 mg/wk

b. iodide di absorbed dari intestine, 80% dg
cepat disekresi
dikidneys, and 20% ditranspotr ke thyroid
gland
Synthesis and Secretion of the Thyroid Metabolic Hormones
• Iodide Pump-the Sodium-Iodide Symporter
(Iodide Trapping)

Fir. 76.2 Thyroid cellular mechanisms for iodine transport, thyroxine and
triiodothyronine formation, and thyroxine and triiodithyronine
release into the blood
Synthesis and Secretion of the Thyroid Metabolic Hormones

• Iodide Pump-the Sodium-Iodide Symporter

(Iodide Trapping)

a. Transport iodine dari darah

b. Formation and secretion thyroglobulin oleh
thyroid cells
c. Oxidation of the iodide ion
d. Iodination of tyrosine and formation of the thyroid
hormone (organification of thyroid)
 Synthesis and Secretion of the Thyroid Metabolic Hormones

Fig. 76.3 Chemistry of thyroxine and

triiodothyronine formation
Synthesis and Secretion of the Thyroid Metabolic Hormones

e. Storage of thyroglobulin-enough is stored to last the

body for 2-3 months

f. Release of throxine and triiodithyronine-cleaved from

the thyroglobulin kemudian di lepas ke blood

g. Kecepatan secretion per hari; 93% is normally thyroxine

7% triiodothyronine. However, about ½ of the
thyroxine is slowly deiodinated to form the T3 so the
tissues get mainly T3
Synthesis and Secretion of the Thyroid Metabolic Hormones

h. Thyroxine and triodothyronine are transported bound

to plasma proteins

i. Because of the high affinity to the plasma proteins,

the hormone is released very slowly

j. Thyroid hormones have slow onset and long duration

of action
 Physiological Functions of the Thyroid Hormones

• Thyroid Hormones Increase the Transcription of

Large Numbers of Genes

a. Most of the thyroxine secreted by the thyroid is

converted to triiodothyronine (T3)

b. Thyroid hormones activate nuclear receptors

 Physiological Functions of the Thyroid Hormones

Fig. 76.5 Thyroid hormone

activation of target cells
 Physiological Functions of the Thyroid Hormones

•Thyroid Hormones Increase Metabolic

Activity-
(increase the BMR 60-100x)

a. Thyroid hormones meningkatkan jumlah

and activity mitochondria

b. Increase active transport ions yg melewati

cell membrane (sodium and potassium)
 Physiological Functions of the Thyroid Hormones

• Thyroid Hormones Effect on Growth

a. Memacu growth and development brain

selama kehamilan dan first years of
postnatal life

b. Deficiency will retard growth during

growing
years
 Physiological Functions of the Thyroid Hormones

• Effect on Specific Bodily Mechanisms

a. Stimulation kecepatan metabolism- uptake

glucose, dengan meningkatkan: glycolysis, gluconeo-
genesis, absorption, insulin secretion

b. Stimulation fat metabolism-lipids di mobilized

secara cepat dg penurunan simpanan fat, peningkatan
konsentrasi free fatty acid dlm plasma, and percepatan
oxidation free fatty acids dlm cells
 Physiological Functions of the Thyroid Hormones

• Effect on Specific Bodily Mechanisms

c. Increased thyroid hormone menurunkan

concentrations cholesterol, phospholipids, and
triglycerides dlm plasma and vice versa; penurunan
cholesterol secretion in bile

• Increased Requirement for Vitamins

• Increased Metabolic Rate

• Decreased Body Weight

 Physiological Functions of the Thyroid Hormones

• Effect on the Cardiovascular System

a. Increased blood flow and cardiac output

b. Increased heart rate
c. Increased heart strength
d. Normal arterial pressure

• Increased Respiration
• Increased Gastrointestinal Motility
• Excitatory Effects on the CNS
• Muscles React With Vigor
 Physiological Functions of the Thyroid Hormones

• Muscle Tremors with Hyperthyroidism

• Difficulty in Sleeping and Constant Tiredness
With Hyperthyroidism
• Increased Thyroid Hormone Increases the
Secretion of Several Other Endocrine Glands
• Needs to be Normal for Normal Sexual
Function
 Regulation of Thyroid Hormone Secretion

• TSH (Anterior Pituitary) Increases Thyroid Secretion

a. Increased proteolysis of the thyroglobulin

b. Increased activity of the iodide pump
c. Increased iodination tyrosine
d. Increased size and secretory activity of the thyroid
cells
e. Increased number of thyroid cells

• Cyclic AMP Mediates the Stimulatory Effect of TSH-

acting as a second messenger system
 Regulation of Thyroid Hormone Secretion

• Secretion of TSH is Regulated by Thyrotropin-

Releasing Hormone from the Hypothalamus

• Feedback Effect of Thyroid Hormone to Decrease

the Secretion of TSH

Fig. 76.7 Regulation of thyroid secretion

.Iodine dlm makanan dlm bentuk ion iodide ions atau inorganic iodine
or bentuk iodine atoms
Iodide ions di absorbsi secara cepat di small intestine kemdian di
distributed
ke extracellular fluid.
Free iodine direducsi to iodide ions, and absorbed One-third of iodine
absorbed is taken up by the thyroid gland. The remainder is removed
as it passes through the kidneys to be excreted in urine.
Iodine is also lost through perspiration and faeces. The excretion of
iodide protects against the accumulation of toxic levels.
The iodide that enters the thyroid gland is oxidised back to iodine, which
combines with residues of the amino acid tyrosine within the iodine-
storage protein thyroglobulin.
If the hypothalamus detects a fall in the blood thyroxin level, it releases a
substance known as thyroxine releasing factor into the plasma.

.
The TRF travels to the pituitary gland, where it
stimulates, the release into plasma of a hormone called Thyroid Stimulating
Hormone—TSH.
The TSH is transported to the thyroid gland, where it stimulates the production of an
enzyme that acts on thyroglobulin to release the iodine-containing tyrosine residues
from the
protein. These residues are then converted into the two thyroid hormones T3 and T4
which are
released into blood plasma in a ratio of four T4 molecules for each T3 molecule.
They travel to every cell in the body to regulate the processes of energy release, which
determine the overall metabolic rate of the body. Figure 12a gives absorption and
metabolism of iodine. Iodine intake in excess of requirement is excreted primarily
through the urine; urinary iodine is a good measure of iodine status.
The steps in this process are as follows:
The Na+/I- symporter transports two sodium ions across the basement membrane
of the follicular cells along with an iodide ion. This is a secondary active
transporter that utilises the concentration gradient of Na+ to move I- against its
concentration gradient.
I- is moved across the apical membrane into the colloid of the follicle.
Thyroperoxidase oxidises two I- to form I2. Iodide is non-reactive, and only the
more reactive iodine is required for the next step.
The thyroperoxidase iodinates the tyrosyl residues of the thyroglobulin within the
colloid. The thyroglobulin was synthesised in the ER of the follicular cell and
secreted into the colloid.
Iodinated Thyroglobulin binds megalin for endocytosis back into cell.
Thyroid-stimulating hormone (TSH) released from the pituitary gland binds the
TSH receptor ( a Gs protein-coupled receptor) on the basolateral membrane of the
cell and stimulates the endocytosis of the colloid.
The endocytosed vesicles fuse with the lysosomes of the follicular cell. The
lysosomal enzymes cleave the T4 from the iodinated thyroglobulin.
These vesicles are then exocytosed, releasing the thyroid hormones.
Effect of iodine deficiency on thyroid hormone synthesis
If there is a deficiency of dietary iodine, the thyroid will not be
able to make thyroid hormone.
The lack of thyroid hormone will lead to decreased negative
feedback on the pituitary, leading to increased production of
thyroid-stimulating hormone, which causes the thyroid to
enlarge (the resulting medical condition is called endemic colloid
goiter; see goiter).
This has the effect of increasing the thyroid's ability to trap
more iodide, compensating for the iodine deficiency and
allowing it to produce adequate amounts of thyroid hormone.