BLOOD

BIOCHEMISTRY
Disusun Oleh:
dr. Husnil Kadri, M.Kes
Biochemistry Departement
Medical Faculty Of Andalas University
Padang

BIOSINTESIS HEMOGLOBIN
(PORFIRIN)

Struktur Porfirin

Porfirin adalah senyawa siklik yg

dibentuk oleh 4 cincin pirol.
Masing-masing cincin dihubungkan oleh
4 jembatan metenil (-HC=).
Sifat
khas
porfirin
adalah
atom
nitrogennya mampu mengikat ion
logam.
Contoh;
- heme pada Hb mengikat Fe
- klorofil pada tumbuhan hijau mengikat
Mg
3

Beberapa Hemoprotein
Protein

Fungsi

- Hemoglobin
mengangkut oksigen di dalam
darah
- Mioglobin
menyimpan oksigen di dalam
otot
- Sitokrom c
keterlibatan pada rantai
transpor elektron
- Sitokrom
P450
hidroksilasi xenobiotik
- Katalase
degradasi hidrogen peroksida
- Triptofan
pirolase
oksidasi triptofan
4

Sintesis Heme di Mitokondria

85% sintesis heme terjadi dalam sel

pembentuk eritrosit pada sumsum
tulang
Heme disintesis dari suksinil KoA +
glisin.
Piridoksal fosfat diperlukan untuk
mengaktifkan glisin.
5

Sintesis Heme di Mitokondria

Pengaturan Sintesis Heme

Enzim regulator adalah ALA-sintase.

Heme bertindak sebagai regulator

negatif (umpan balik negatif) sintesis
enzim ALA- sintase.

Jika heme meningkat, maka sintesis

ALA-sintase akan menurun.
7

Porfiria

Merupakan
gangguan
genetik
biosintesis heme.
Umumnya autosomal dominan, kecuali
porfiria eritropoitik kongenital.
Gejala;
- nyeri abdomen
- gangguan neuropsikiatri
- fotosensitifitas kulit
- bila berat = prototipe manusia srigala
8

Fungsi Utama Darah

1. Respirasi;
pengangkutan O2 dan CO2
2. Nutrisi;
pengangkutan hasil absorpsi usus
3. Ekskresi;
pengangkutan sisa metabolik ke ginjal,
paru-paru, kulit, & usus

Fungsi Utama Darah

4. Keseimbangan asam-basa
5. Keseimbangan air;
antara sirkulasi darah dan jaringan
6. Pengaturan suhu tubuh
7. Pertahanan terhadap infeksi;
oleh sel darah putih & antibodi

Fungsi Utama Darah

8. Pengangkutan hormon &
pengaturan metabolisme
9. Pengangkutan metabolit
10. Koagulasi

Components of Whole
Blood
Plasma
(55% of whole blood)
Buffy coat:
leukocyctes and
platelets
(<1% of whole blood)

1 Withdraw blood

2 Centrifuge

and place in tube

Hematocrit
Males: 47% 5%
Females: 42% 5%

Erythrocytes
(45% of whole blood)

Formed
elements

Physical Characteristics of
Blood
Average volume of blood:
56 L for males; 45 L for females (Normovolemia)
Hypovolemia - low blood volume
Hypervolemia - high blood volume
Viscosity (thickness) - 4 - 5 (where water = 1)
The pH of blood is 7.357.45; x = 7.4
Osmolarity = 300 mOsm or 0.3 Osm
This value reflects the concentration of solutes in the
plasma
Salinity = 0.85%
Reflects the concentration of NaCl in the blood
Temperature is 38C, slightly higher than normal body
temperature
Blood accounts for approximately 8% of body weight

Components of Blood
55% plasma
45% cells
99% RBCs
< 1% WBCs and platelets

Blood Plasma
Blood plasma components:
Water = 90-92%
Proteins = 6-8%
Organic nutrients glucose, carbohydrates,
amino acids
Electrolytes sodium, potassium, calcium,
chloride, bicarbonate
Nonprotein nitrogenous substances lactic acid,
urea, creatinine
Respiratory gases oxygen and carbon dioxide

Formed Elements
Formed elements comprise 45% of
blood
Erythrocytes, leukocytes, and platelets
make up the formed elements
Only WBCs are complete cells
RBCs have no nuclei or organelles, and
platelets are just cell fragments

Most blood cells do not divide but are

renewed by cells in bone marrow

Erythrocytes (RBCs)
Biconcave disc
Folding increases surface area (30% more surface area)
Plasma membrane contains spectrin
Give erythrocytes their flexibility
Anucleate, no centrioles, no organelles
End result - no cell division
No mitochondria means they generate ATP anaerobically
Prevents consumption of O2 being transported

Filled with hemoglobin (Hb) - 97% of cell contents

Hb functions in gas transport
Hb + O2
HbO2 (oxyhemoglobin)
Most numerous of the formed elements
Females: 4.35.2 million cells/cubic millimeter
Males: 5.25.8 million cells/cubic millimeter

Erythrocytes (RBCs)

Figure 17.3

Erythrocyte Function
Erythrocytes are dedicated to respiratory gas
transport
Hemoglobin reversibly binds with oxygen and
most oxygen in the blood is bound to
hemoglobin
Composition of hemoglobin
A protein called globin
made up of two alpha and two beta chains

A heme molecule
Each heme group bears an atom of iron, which can bind to
one oxygen molecule
Each hemoglobin molecule thus can transport four
molecules of oxygen

Structure of Hemoglobin

Figure 17.4

Hemoglobin

Satu mol. Hb dewasa (HbA) mempunyai;

- 4 gugus heme
- Setiap heme mengandung 1 ion Fe2+
- 4 subunit protein globin
- Setiap subunit mengikat 1 mol. O 2
- 1 mol. Globin mengikat 1 mol. CO 2

Subunit rantai terdiri dari 2 dan 2

- masing-masing=141 asam amino
- masing-masing = 146 asam amino

Hemoglobin
Oxyhemoglobin hemoglobin bound to oxygen
Oxygen loading takes place in the lungs
Deoxyhemoglobin hemoglobin after oxygen
diffuses into tissues (reduced Hb)
Carbaminohemoglobin hemoglobin bound to
carbon dioxide
Carbon dioxide loading takes place in the
tissues

WBC Anatomy and Types

All WBCs (leukocytes) have a nucleus and
no hemoglobin
Granular or agranular classification based
on presence of cytoplasmic granules made
visible by staining
granulocytes are neutrophils, eosinophils or
basophils
agranulocytes are monocyes or lymphocytes

Differential WBC Count

Detection of changes in numbers of circulating
WBCs (percentages of each type)
indicates infection, poisoning, leukemia,
chemotherapy, parasites or allergy reaction

Normal WBC counts

neutrophils 60-70% (up if bacterial infection)
lymphocyte 20-25% (up if viral infection)
monocytes 3 - 8 % (up if fungal/viral infection)
eosinophil 2 - 4 % (up if parasite or allergy reaction)
basophil <1% (up if allergy reaction or hypothyroid)

Neutrophils (Granulocyte)
Polymorphonuclear Leukocytes or Polys
Nuclei = 2 to 5 lobes connected by thin strands
older cells have more lobes
young cells called band cells because of horseshoe
shaped nucleus (band)

Fine, pale lilac practically invisible granules

Diameter is 10-12 microns
60 to 70% of circulating WBCs

Eosinophils (Granulocyte)
Nucleus with 2 or 3 lobes connected by
a thin strand
Large, uniform-sized granules stain
orange-red with acidic dyes
do not obscure the nucleus

Diameter is 10 to 12 microns
2 to 4% of circulating WBCs

Basophils (Granulocyte)
Large, dark purple, variable-sized
granules stain with basic dyes
obscure the nucleus

Irregular, s-shaped, bilobed nuclei

Diameter is 8 to 10 microns
Less than 1% of circulating WBCs

Lymphocyte (Agranulocyte)
Dark, oval to round nucleus
Cytoplasm sky blue in color
amount varies from rim of blue to normal
amount

Small cells 6 - 9 microns in diameter

Large cells 10 - 14 microns in diameter
increase in number during viral infections

20 to 25% of circulating WBCs

Lymphocytes
B cells - responsible for humoral immunity
T cells - responsible for cell mediated
immunity

B cells responsible for production of

antibodies
Receptor matches antigen
Cells multiply
Antibodies

 T cells
Cytotoxic T cells (Killer T cells)
Bind to cytotoxic cells (eg infected by virus)
Swell
Release toxins into cytoplasm

Helper T cells
Most numerous
Activate B cells, killer T cells
Stimulate macrophages

Suppressor T cells
Regulate activities of other cell types

Monocyte (Agranulocyte)
Nucleus is kidney or horse-shoe shaped
Largest WBC in circulating blood
does not remain in blood long before migrating to the tissues
differentiate into macrophages
fixed group found in specific tissues
alveolar macrophages in lungs
kupffer cells in liver

wandering group gathers at sites of infection

Diameter is 12 - 20 microns
Cytoplasm is a foamy blue-gray
3 to 8% o circulating WBCs

UNSUR SELULAR DALAM RESPON IMUN

1. Jalur limfoid yang membentuk limfosit

dan subsetnya
2. Jalur mieloid yang membentuk sel-sel
fagosit mononuklear & polimorfonuklear
(PMN).
PMN terdiri dari:
neutrofil, eosinofil, basofil

Platelets
Platelets are
karyocytes

fragments

of

mega-

Platelets function in the clotting

mechanism by forming a temporary
plug that helps seal breaks in blood
vessels

Protein Plasma
- Bagian utama unsur padat dalam plasma.
- Konsentrasi total protein plasma + 7-7,5 g/dl.
- Berbagai protein plasma dapat dipisahkan
menurut karakteristik kelarutannya.
- Metode pemisahan tsb antara lain;
1. Salting-out (Na2SO4 23%, dll)
2. Elektroforesis

Protein Plasma
1. Sebagian besar disintesis di hepar.
2. Umumnya disintesis sbg preprotein pada
poliribosom terikat membran. Preprotein
akan mengalami modifikasi pascatranslasi.
3. Hampir semuanya berupa glikoprotein,
kecuali albumin.
4. Bersifat polimorfisme (ciri bawaan pd
populasi dgn sedikitnya 2 macam fenotipe).
contoh; gol. Darah ABO

Plasma Proteins
More than 200
Most abundant
Albumin - 4-5 g/100 mL
--globulins - ~1 g/100 mL
fibrinogen - 0.2-0.4g/100 mL

Albumin
- Merupakan protein utama dalam plasma.
- Mempertahankan 75-80% tekanan osmotik.
- Berfungsi mengikat berbagai macam ligand,
seperti; asam lemak bebas, Ca, Cu, Zn,
hormon steroid, bilirubin, metheme

Albumin
- Albumin juga dapat mengikat obat-an,
seperti; sulfonamid, penisilin-G,
dikumarol, aspirin
-

Penyakit hepar akan memperlihatkan rasio

albumin/globulin yang menurun.

Transferin

Adalah 1-globulin berbentuk glikoprotein

yang disintesis di hepar.

Berfungsi sebagai alat transpor besi (Fe 3+)

untuk dibawa ke jaringan.

Jika besi tidak diikat oleh transferin, maka

akan menjadi prooksidan.

Ceruloplasmin

Protein ini adalah 2-globulin yang

mengandung 90% Cu plasma.
Tetapi 10% Cu terikat longgar pd albumin,
sehingga mudah dilepas ke jaringan.

Ceruloplasmin mengandung ferroksidase

yang mengkatalisis ion Fe2+ --> Fe3+,
karena hanya ion Fe3+ yang mampu
berikatan dgn apotransferin.

 -Globulins
20% of plasma proteins
refers to electrophoretic mobility
Represents a group of proteins of
variable structure
immunoglobulins
Main functional task is immunochemical
Antibodies - combine with specific
antigens

Imunoglobulin Plasma

Disintesis dalam sel plasma.

Sel plasma adalah turunan Sel- yang

mensintesis dan mensekresikan imunoglobulin sebagai respon terhadap pajanan
berbagai antigen.

Semua imunoglobulin mengandung paling

kurang 2 rantai ringan dan 2 rantai berat.

Classes of Immunoglobulins
IgG Identifies microorganisms for engulfment
or lysis
IgE Inhibits parasite invasion; involved in
allergic reactions
IgD Unknown
IgA Basis for passive immunity provided by
breast milk, agglutinates infectious agents in
secretions outside the body, present in tears,
mucous
IgM Identifies microorganisms for engulfment
or lysis

 Basic 4 chain structural unit

MW = 2x55000 +2x27000 = 160000

Haptoglobin

Merupakan glikoprotein plasma yang

mengikat hemoglobin ekstrakorpuskular.

Membentuk komplek Hb-Hp (HemoglobinHaptoglobin).

Hb ekstrakorpuskular merupakan hasil

penguraian + 10% Hb yang dilepas ke dlm
sirkulasi.

Kepustakaan

Marks, DB., Marks, AD., Smith CM. 1996. Basic medical

biochemistry: a clinical approach. Dalam: B.U. Pendit,
penerjemah.
Biokimia Kedokteran Dasar: Sebuah
Pendekatan Klinis. Eds. J. Suyono., V. Sadikin., L.I.
Mandera. Jakarta: EGC, 2000: 612 - 4.

Murray, RK. 2003. Porfirin dan pigmen empedu. Dalam:

Andry Hartono, penerjemah. Harpers Biochemistry. 25th
ed. Eds. R.K. Murray, D.K. Granner, P.A. Mayes, V.W.
Rodwell. McGraw-Hill Companies, New York: 342 - 9.

Schumm, DE. 1992. Essentials of biochemistry. Dalam:

Moch. Sadikin, penerjemah. Intisari Biokimia. Jakarta:
Bina Aksara, 1993: 147.
50

Kepustakaan

Harbut, C. 150 Blood. Download 19-10-2010.

http://www.cerritos.edu/charbut/AP150/lec_otl/150%20Blood.ppt

Rand, ML., Murray, RK. 2003. Protein plasma, imunoglobulin, dan

pembekuan darah.
Dalam: Andry Hartono, penerjemah. Harpers
Biochemistry. 25th ed. Eds. R.K. Murray, D.K. Granner, P.A. Mayes, V.W.
Rodwell. McGraw-Hill Companies, New York: 702 - 11.

Simpson, S. Chapter 19 Blood. Download 19-10-2010.

Sheardown, H. Blood Biochemistry. McMaster University. Download 20-052007.