1. Chapter 16 Hemal Biochemistry The biochemistry and molecular biology department of CMU

2. Composition of the blood –The liquid element: plasma –The formed elements: red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes). Plasma --- The blood fraction obtained after removal of the cellular components. Serum --- The liquid element obtained by allowing the blood to clot.

3. §1 Heme Synthesis

4. Sites: Mitochondria and cytoplasm Precursors: Glycine, succinyl CoA, Fe 2+

5. 1. Synthetic pathway of heme (1) The formation of  -aminolevulinic acid (ALA) + HSCoA + CO 2 ALA synthase (pyridoxal phosphate) In the mitochondria

6. (2) The formation of porphobilinogen (PBG) ALA dehydratase 2H 2 O In the cytosol

7. (3) The formation of uroporphyrinogen Ⅲ (UPG Ⅲ ) and coproporphyrinogen Ⅲ (CPG Ⅲ ) 4× Porphobilinogen Linear tetrapyrrol UPG Ⅲ CPG Ⅲ Deaminase UPG Ⅲ isomerase UPG Ⅲ decarboxylase In the cytosol

8. Protoporphyrinogen Ⅸ Protoporphyrin Ⅸ Heme ferrochelatase (4) The formation of heme CPG Ⅲ oxidase CPG Ⅲ Protopor- phyrinogen Ⅸ oxidase In the mitochondria

9. Heme Protoporphyrin Ⅸ Protoporphyrinogen Ⅸ CPG Ⅲ UPG Ⅲ Linear tetrapyrrol PBG Gly succinyl CoA

10. (1) ALA synthase Rate-limiting enzyme Feedback-inhibition by heme Intensity inhibition by Ferriheme Inducing by some drugs and hormones (eg. testosterone) 2. Regulation of heme biosynthesis

11. (3) Erythropoietin (EPO) can increase synthesis of heme and hemoglobins. (2) ALA dehydrase and ferrochelatase Inhibited by heme, and heavy metals.

12. §2 Metabolism of Bile Pigment and Jaundice

13. bile pigment is the main catabolic product of iron porphyrin compound in the body, consisting of bilirubin, biliverdin, bilinogen and bilin.

14. ＊ The source of bilirubin The compounds involving iron prophyrin in the body are hemoglobin, myoglobin, cytochrome, peroxidase, and catalase, etc. 1. Formation and transport of bilirubin

15. ＊ Formation of bilirubin site In the microsome and cytosol of monokaryon- macrophage system of the liver, spleen, and bone marrow.

16. process

17. The spatal structure of bilirubin property hydrophobic

18. ＊ Transport of Bilirubin Form of Transport Bilirubin-albumin complex

19. 2. Bilirubin conversion in liver ＊ Uptake ＊ Transport Smooth Endoplasmic reticulum Combine with ligandin

20. ＊ Conjugation Bilirubin monoglucuronide bilirubin UDP UDP- glucuronyl transferase UDPGA Bilirubin diglucuronide UDPGA UDP UDP- glucuronyl transferase

21. structure of bilirubin diglucuronide

22. ＊ Excretion Conjugated bilirubin is secreted into the bile and then excreted into the intestine.

23. Conjugated bilirubin bilinogen coliform Glucuronic acid Bilin oxidized ＊ process 3. Metabolism bilirubin in the intestine Free bilirubin reduced

25. 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.

27. 4. Serum bilirubin and jaundice Conjugated bilirubin is also called direct reacting bilirubin or hepatobilirubin. ＊ Serum bilirubin 1 ～ 16  mol/l (0.1 ～ 1mg/dl) Free bilirubin is also called indirect reacting bilirubin or hemobilirubin.

28. free bilirubin conjugated bilirubin Binding with Glucuronic acid no yes Reacting with the diazo reagent Slow and indirect Rapid and direct solubility in watersmalllarge Discharged via kidneynoyes Pass through the membrane of cell yesno difference of two bilirubins

29. Jaundice Hemolytic (prehepatic) jaundice Hepatocellular (hepatic) jaundice Obstructive (posthepatic) jaundice

30. Laboratory results in patients with jaundice normal Hemolytic jaundice Hepatocellular jaundice Obstructive jaundice Serum bilirubin total < 1mg/dl > 1 > 1 > 1 direct 0~ 0.8mg/dl ↑ indirect < 1 Urine bile pigments urobilirubin ––+ urobilinogenA few ↑ uncertainty ↓ urobilinA few ↑ uncertainty ↓ Color of fecesnormaldark Simple or normal Clay color ↑ ↑ ↑