BIOKIMIA DARAH

Departemen Biokimia
FK UMSU
2015
 THE HEME GROUP
Each subunit of hemoglobin or myoglobin contains a heme.
•Binds one molecule of oxygen
•Heterocyclic porphyrin derivative
•Specifically protoporphyrin IX

The iron must be in the Fe(II)

form or reduced form. (ferrous
oxidation) state.
The heme alone interacts with oxygen
such that the Fe(II) becomes oxidized to
Fe(III) and no longer binds oxygen.
When Fe(II) goes to Fe(III), oxidized, it
produces methemoglobin which is brown and
coordinated with water in the sixth position.
Dried blood and old meat have this brown
color.
Butchers use ascorbic acid to reduce methemoglobin to make the meat look fresh!!
There is an enzyme methemoglobin reductase that converts methemoglobin to
regular hemoglobin.
The globin surrounds the heme like a hamburger is
surrounded by a bun. Only the propionic acid side
chains are exposed to the solvent.
Amino acid mutations in the heme pocket can
cause autooxidation of hemoglobin to form
methemoglobin.

The globin acts to:

•a. Modulate oxygen binding
affinity
•b. Make reversible oxygen
binding possible
HEMOGLOBIN
•Transports oxygen from lungs to tissues.
•Solubility of O2 is low in plasma  bound to hemoglobin
•Two alternative O2 transporters are;
•Hemocyanin, a Cu containing protein.
•Hemoerythrin , a non-heme containing protein.

MYOGLOBIN
The rate of O2 diffusion from capillaries to tissue is slow
because of the solubility of oxygen.
Myoglobin increases the solubility of oxygen.
Myoglobin facilitates oxygen diffusion.
 MYOGLOBIN

Physico-chemical properties
• 153 amino acids – single polypeptide chain
• Very compact: globular structure  little empty space for
solution to get in
• Tertiary structure: 8 alpha helices (A-H), 4 helices terminated by
proline residues
• About 75% is in alpha helical structure
• Polar side chains on outside of protein interact with solution
• Myoglobin = storage protein mainly in skeletal muscle
• High O2 affinity – does not change with concentration
• Monomer  no cooperativity
The Backbone structure of Myoglobin 1
1
 STRUCTURE HEMOGLOBIN

• Primary, secondary and tertiary structures are same as Mb

• More than 1 subunit  quaternary structure:
1. 2 α and 2 β subunits; cooperativity in binding and release of O2
a. β subunits: 146 residues, identical (same gene)
b. α : 141 residues, differ by 1 or 2 genes
2. In urea, Hb dissolves into dimers of α/β-  α-β interaction is
stronger than α-α or β-β
3. Tetramer is globular molecule: spherical
Subunits are 2.5nm apart  cooperativity is not due to heme-heme
interaction; affinity of O2 varies with concentration (also with pH,
CO2, 2,3 biphos. - see c)
Quaternary structure of deoxy- and oxyhemoglobin

T-state R-state
• Enzim-enzim dalam proses biosintesa heme
juga protein.
• Sintesa protein mengikuti proses transkripsi
dan translasi,dimana informasi kandungan
asam amino dari protein ditentukan oleh
kode genetika pada mRNA.
• Kelainan genetik kemungkinan
menyebabkan kelainan globin atau enzim-
enzim yg mengkatalisir sintesa Heme.
 PORPHYRIN

Porphyria: sekelompok penyakit yang

disebabkan kelainan pada jalur biosintesa
berbagai porphyrin.
Porphyrin : senyawa siklis yg dibentuk oleh 4
cincin pyrrolemelalui jembatan —HC=.
Protein yg mengandung heme termasuk
hemoprotein.
 ACUTE INTERMITTEN PORPHYRIA
Tanda-tanda penting:
-Intermitten abdominal pain.
- Penyebab nyeri abdomen: neurologik.
-Seizure ,psychosis.
-Hyponatremia.
-Mutasi porphobilinogen deaminase gen
THALASSEMIA
-Globin dari Hb A disusun oleh 2 rantai- dan 2 rantai-.
-Terjadi reduksi sintesa rantai globin.
-Hypochromic microcytic anemia.
-Thalassemia - : delesi gen.
-Thalassemia- : point mutation.
 DEFECTS IN HEMOGLOBIN STRUCTURE AND DISEASE

• Sickle Cell Disease  Malaria  Mutation in Hb globin gene

Other Hemoglobin variants
i. Hemoglobin S …….. ß6 Glu  Val
ii. Hemoglobin C………. ß6 Glu  Lys – very little consequence
iii. Hemoglobin E ………. ß26 Glu Lys – very little consequence
iv. Hemoglobin Constant Spring (a-globin chain that is abnormally
long)
v. Hemoglobin H …(ß4)- high affinity, doesn’t deliver O2 very well
vi. Hemoglobin Barts………(γ4) – fetus usually dead before birth
• Thalassemias  One or more genes coding for Hb chains are
deleted –called α or β
TERIMA KASIH