biokimia mineral -...

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

(PTH) Organ-target: bones, kidneys

Function of PTH - increase 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

Vitamin D Thyreocalcitonin

Organ-target - bones

Function - decrease of Ca

concentration in plasma

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

feedback

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

Calsium diabsorsi di semua bagian

small intestine, paling cepat di bagian

duodenum, dlm kondisi acidic medium

(pH < 7) prevails

Absorption, Transport, Storage,

and Excretion

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.

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.

REGULATION OF SERUM

CALCIUM (lanjutan)

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: - Body need

- Vitamin D

- Protein

- Lactose

- Acid medium

Absorption decreased by: - Vitamin D deficiency

- Calcium-phosphorus imbalance

- Oxalic acid

- Phosphorous

- Dietary fiber

- Excessive fat

- High alkalinity

- Also stresses and lack of exercise

Excretion increased by: - Low parathyroid hormone (PTH)

- High extracellular fluid volume

- High blood pressure

- Low plasma phosphate

- Metabolic alkalosis

Excretion decreased by: - High parathyroid hormone

- Low extracellular fluid volume

- Low blood pressure

- High plasma phosphate

- Metabolic acidosis

- Vitamin D3

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

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.

Absorption, Transport, Storage, and Excretion

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

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)


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

Absorption, Transport, Storage, and Excretion (lanjutan)

Figure 5-5 Magnesium Balance is maintained largely by GI

Absorption and Renal Excretion

Magnesium Balance

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

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

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.


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


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


• 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


• 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


• 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)


Fig. 76.3 Chemistry of thyroxine and

triiodothyronine formation


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 and

7% triiodothyronine. However, about ½ of the

thyroxine is slowly deiodinated to form the T3 so the

tissues get mainly T3


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


Fig. 76.5 Thyroid hormone

activation of target cells


• 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)


• 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


• 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


• 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


• 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


• 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.

http://en.wikipedia.org/wiki/Iodine_deficiency

http://en.wikipedia.org/wiki/Negative_feedback

http://en.wikipedia.org/wiki/Negative_feedback

http://en.wikipedia.org/wiki/Thyroid-stimulating_hormone



http://en.wikipedia.org/wiki/Goiter

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