血液生化英文版

δ
β
2O2 Fe3+ CO heme oxygenase
γ
COOH
P P bilirubin
• property
hydrophobic
H O C
O N H OO HO
C
The spatal structure of bilirubin
＊ Transport of Bilirubin
difference of two bilirubins
free bilirubin Binding with Glucuronic acid Reacting with the diazo reagent solubility in water Discharged via kidney no Slow and indirect small no yes conjugated bilirubin yes Rapid and direct large yes no
Pass through the membrane of cell
Jaundice
• Hemolytic (prehepatic) jaundice • Hepatocellular (hepatic) jaundice • Obstructive (posthepatic) jaundice
Laboratory results in patients with jaundice
O H N H N H H H N H N O
H2C CH2 CO COOH H O H OH H H H HO O
CH2 CH2 CO O COOH O H H HO H H OH H
OH
OH
＊ Excretion Conjugated bilirubin is secreted into the bile and then excreted into the intestine.
bilirubin glucuronide
bilin feces
bilirubin
glucuronic acid
urine
4. Serum bilirubin and jaundice
＊ Serum bilirubin 1～16mol/l (0.1 ～1mg/dl) • Conjugated bilirubin is also called direct reacting bilirubin or hepatobilirubin. • Free bilirubin is also called indirect reacting bilirubin or hemobilirubin.
3. Metabolism bilirubin in the intestine
＊process
Conjugated bilirubin coliform Free bilirubin reduced
Glucuronic acid oxidized Bilin
bilinogen
H HO N
H N
normal Serum bilirubin total direct indirect < 1mg/dl 0~ 0.8mg/dl <1 ↑↑ > 1mg/dl > 1mg/dl ↑ ↑ > 1mg/dl ↑↑ Hemolytic jaundice Hepatocellular jaundice Obstructive jaundice
monokaryon-macrophage cell Hb globin heme
NADPH+H+
blood
liver cell bilirubin cytosol
bilirubin-albumin complex
ligandin
bilirubin-ligandin complex
2O2 Fe3+ H2O +CO biliverdin
(1) ALA synthase
• Rate-limiting enzyme
• Feedback-inhibition by heme
• Intensity inhibition by Ferriheme
• Inducing by some drugs and hormones (eg. testosterone)
H
H
H N
H
N
OH
P P
bilirubin
+8H H HO N H P P H H N H H H N H H H N OH +8H
d-urobilinogen
2H HO
H N
H
H
H N
H
H
H N
H
H
H N
OH
d-urobilin
+4H H H H P P
P P
mesobilirubinogen
HO H
• Plasma --- The blood fraction obtained after removal of the cellular components.
• Serum --- The liquid element obtained by allowing the blood to clot.
NADP+
UDPGA ER UDP bilirubin glucuronide a large fraction bilinogen (a little) a small fraction O2 intestine
NADPH+H+ NADP+
bilirubin
kidney bilinogen
bilinogen O2 bilin
• Form of Transport Bilirubin-albumin complex
2. Bilirubin conversion in liver
＊ Uptake ＊ Transport
Combine with ligandin
Smooth Endoplasmic reticulum
＊ Conjugation
COOH H2C CH2
COOH
+
CH2NH2 COOH
HSCoA + CO2
H2C CH2
C ～ SCoA O
ALA synthase (pyridoxal phosphate)
C
O
CH2NH2
In the mitochondria
(2) The formation of porphobilinogen (PBG)
(2) ALA dehydrase and ferrochelatase
Inhibited by heme, and heavy metals.
(3) Erythropoietin (EPO) can increase synthesis of heme and hemoglobins.
§2
Metabolism of Bile Pigment and Jaundice
• site
In the microsome and cytosol of monokaryon- macrophage system of the liver, spleen, and bone marrow.
• process
α
Ⅰ N N Fe2+ Ⅳ N N Ⅲ Ⅱ NADPH+H+ NADP+ O H N N H N P P biliverdin NADPH+H+ HOOC heme O H N H N H H biliverdin reductase NADP+ H N H N O H N O
COOH
O
CH2 CH2 O H H C C N
HO
OH
ALA O H dehydratase
H
2H2O
H2N
N H
In the cytosol
(3) The formation of uroporphyrinogen Ⅲ (UPGⅢ) and coproporphyrinogen Ⅲ (CPGⅢ)
Heme
ferrochelatase
Protoporphyrin Ⅸ
In the mitochondria
PBG
Heme
Gly succinyl CoA
Protoporphyrin Ⅸ
Linear tetrapyrrol
Protoporphyrinogen Ⅸ
CPGⅢ
UPGⅢ
2. Regulation of heme biosynthesis
H N
H H
H
H N
H
H
H N
H N
OH H
2H
stercobilin (l-urobilin)
stercobilinogen (l-urobilinogen)
Bilinogen enterohepatic circulation
In the terminal ileum and large intestine, a small fraction of the urobilinogens is reabsorbed and reexcreted through the liver to constitute the enterohepatic cycle of urobilinogen.
＊The source of bilirubin The compounds involving iron prophyrin in the body are hemoglobin, myoglobin, cytochrome, peroxidase, and catalase, etc.
＊Formation of bilirubin
§1 Heme Synthesis
Sites: Mitochondria and cytoplasm
Precursors: Glycine, succinyl CoA, Fe2+
1. Synthetic pathway of heme
(1) The formation of -aminolevulinic acid (ALA)
Chapter 16
Hemal Biochemistry
The biochemistry and molecular biology department of CMU
• Composition of the blood
– The liquid element: plasma
– The formed elements: red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes).
bilirubin UDPGA UDPglucuronyl transferase
UDP
Bilirubin monoglucuronide
UDPGA
UDPglucuronyl transferase
UDP
Bilirubin diglucuronide
structure of bilirubin diglucuronide
4× Porphobilinogen
Deaminase Linear
tetrapyrrol
UPG Ⅲ isomerase
CPGⅢ In the cytosol
UPGⅢ decarboxylase
UPGⅢ
(4) The formation of heme
CPGⅢ oxidase
CPGⅢ
Protoporphyrinogen Ⅸ Protoporphyrinogen Ⅸ oxidase
bile pigment is the main catabolic product of iron porphyrin compound in the body, consisting of bilirubin, biliverdin, bilinogen and bilin.
1. Formation and transport of bilirubin
Urine bile pigments urobilirubin urobilinogen urobilin Color of feces – A few A few normal – ↑ ↑ dark ++ uncertainty uncertainty ++ ↓ ↓
Simple or normal Clay color