HEME

dr. Septi Handayani, M.Si.

 globin
hemoglobin
heme
 Hemoglobin (Hb)
• Hb ada bbp macam dilihat dari ontogenesis
(tumbuh-kembang individu) & dari distribusi di
bbg jar.
• Hb yang terbanyak: dalam darah
• Salah satu protein terbanyak ([Hb] darah 15 g/
dL. Bila vol darah total orang dws 5L, total Hb:
750 g)
• Memberi warna merah pada darah o/ pigmen
Hem : Fe-porfirin (bukan proteingugus
prostetik
Struktur Hem
• Hem:Fe-porfirin
• Porfirin dibntk o/ 4
cincin pirol
• Fe di tgh cincin, bntk
ikatan koordinasi dg
N pirol
• Koord dg N histidin
globin
• Hrs Fe2+ u/ ikat O2
• Hb (HbA) protein tetramer:2 globin  & 2 globin 
(22).
• Hb F(jabang bayi): 22
• Beda:afinitas thdp O2 dari HbF>HbA
• Pada tiap globin terikat 1 hem, di antar 2 heliks-
• Kurva saturasi dari Hb terhadap O2 agak berbeda
dg kurva Michaelis-Menten
• Kurva tsb berbentuk sigmoid (=mirip huruf sigma
atau S)
 Kurva Saturasi & Disosiasi Hb pada
Beberapa Keadaan
Saturasi bbg Hb & Mb Pengaruh CO2 pd disosiasi Hb
 Hb jaringan
• Selain Hb darah, juga ada Hb jaringan.
• Hb darah: tetramer (22 atau 22)
• Hb jaringan: monomer, berbeda antar jaringan
• Otot lurik (rangka&jantung) : mioglobin (Mb)
• SSP : neuroglobin (Ngb)
• Sel lain:sitoglobin (cytoglobin,Cygb)
• Fungsi & sifat :
• Hb jaringan berfungsi mengikat O2 yg dilepas HbO2 di
jaringan, lgsg ditangkap sel & diikat Hb jar  mitokondria
• Kurva saturasi>hiperbola (monomer Hb darah jg dmkn)
• BM  =monomer Hb darah, 15-19 kD
• Hb jaringan juga berfgs sbg antioksidan sel ybs
• Cedera otot lurikMb di drh & urin
• Peran Fe dalam Hb :
• Mengikat O2 ,u/ itu hrs sbg Fe2+
• Ttp Fe dpt teroksidasiFe3+ tdk dpt ikat O2.
• Hb teroksidasiHbO2.
• Hb teroksidasi=Hb(Fe3+)=metHB
• Hb tereduksi =Hb(Fe2+)
• Hb teroksigenasi=oksiHb=HbO2 & tepatnya Hb(Fe2+)O2
• Hb(Fe2+) tanpa O2> tepat disbt deoksiHb
• MetHb direduksi jd Hb o/metHb reduktase
 Perbandingan Mb & Hb

Mb & monomer Hb Hb (tetramer globin)

Pembentukan Heme
PORPHYRINS
HC CH • NOMENCLATURE
• Types of substituents
HC CH • Symmetry I or III
• Oxidation between rings
N • Methylene -CH2-
H • Methene -CH=

Pyrrole ring
PEMBENTUKAN
HEME
Katabolisme Hb
 FATE OF RED BLOOD CELLS

• Life span in blood stream is 60-120 days

• Senescent RBCs are phagocytosed and/or lysed

• Normally, lysis occurs extravascularly in the

reticuloendothelial system subsequent to RBC phagocytosis

• Lysis can also occur intravascularly (in blood stream)

Extravascular Pathway for RBC Destruction
(Liver, Bone marrow,
& Spleen)

Phagocytosis & Lysis

Hemoglobin

Globin Heme Bilirubin

Amino acids Fe2+

Amino acid pool Excreted

Katabolisme Heme
Heme Degradation
Fig. 44.7
Page 839
Reactions
Fig. 44.8
Page 840
 DEGRADATION OF HEME TO BILIRUBIN

 75% is derived from RBCs

· In normal adults this results in a

daily load of 250-300 mg of
P450 cytochrome
bilirubin

· Normal plasma concentrations

are less then 1 mg/dL

· Hydrophobic – transported by
albumin to the liver for further
metabolism prior to its excretion

“unconjugated” bilirubin
NORMAL BILIRUBIN · Uptake of bilirubin by the liver is mediated by a carrier
METABOLISM protein (receptor)

· Uptake may be competitively inhibited by other

organic anions

· On the smooth ER, bilirubin is conjugated with

glucoronic acid, xylose, or ribose

· Glucoronic acid is the major conjugate - catalyzed by

UDP glucuronyl tranferase

·“Conjugated” bilirubin is water soluble and is secreted

by the hepatocytes into the biliary canaliculi

· Converted to stercobilinogen (urobilinogen) (colorless)

by bacteria in the gut

· Oxidized to stercobilin which is colored

· Excreted in feces

· Some stercobilin may be re-adsorbed by the gut and

re-excreted by either the liver or kidney
Terima kasih