IV. การสังเคราะห์สารชีวโมเลกุลพิเศษ

งานนำเสนอเรื่อง: "IV. การสังเคราะห์สารชีวโมเลกุลพิเศษ"— ใบสำเนางานนำเสนอ:

1 IV. การสังเคราะห์สารชีวโมเลกุลพิเศษ
แบ่งเป็นกลุ่มดังนี้ 1. จาก Tyr ( catecholamines, melanin, thyroid hormones) 2. จาก Trp (serotonin, melatonin) 3. จาก Glu (gamma-aminobutyrate, GABA) 4. จาก His (histamine) 5. Creatine phosphate 6. Polyamines 7. NO 8. Porphyrins and Bile pigments

2 1. จาก Tyr ( catecholamines, melanin, thyroid hormones)

3 Catecholamines Parkinson’s disease Cu2+, ascorbate

4 Catecholamines catabolism
Adrenal pheochromocytoma diagnosis

5 Melanin Albinism Cu2+

6 Thyroid hormones

7 2. จาก Trp (serotonin, melatonin)
-vasoconstrictor -อารมณ์ -อุณหภูมิร่างกาย -ความอยากรับประทานอาหาร -การหลับ -การอาเจียน

8 2. จาก Trp (serotonin, melatonin)
-circadian rhythms -เป็นยาบรรเทาอาการ jet-lag

9 3. จาก Glu (GABA) PLP-dep enz พบใน gray matter
Murray RK, et.al. p.342, 1996

10 4. จาก His (histamine) Campbell PN, Smith AD, p.113, 2000

11 4. Creatine phosphate Marks DB, et.al. p.626, 1996 Muscle and brain

12 4. Creatine phosphate -ค่า Creatinine ในปัสสาวะเป็นค่าคงที่ ใช้เทียบการขับออกของสารอื่น -ค่า Creatine ในเลือด บอกการทำงานของไต -Creatinuria พบเมื่อ เป็นไข้ ขาดอาหาร เบาหวาน hyperthyroidism musculardystrophy

13 5. Polyamines

14 Catabolism of polyamines
Murray RK, et.al. p.337, 1996

15 6. Nitric oxide NO : หลอดเลือดขยายตัว ยับยั้งการแข็งตัวของเลือด ทำงานร่วมกับสารสื่อประสาท กระตุ้น guanylate cyclase (cGMP-->PK, cGMP ถูกทำลายด้วย cGMP phosphodiesterase, Sildenafil)

16 7. Porphyrins and bile pigments
Heme

17 Biosynthesis of heme I

18 Biosynthesis of heme II

19 Biosynthesis of heme III

20 Biosynthesis of heme IV

21 Biosynthesis of heme V

22 Biosynthesis of heme VI

23 Biosynthesis of heme VII

24 Biosynthesis of heme

25 Catabolism of heme

26 Catabolism of heme

27 Bilirubin diglucuronide in bile Urobilinogens & Stercobilinogens
Catabolism of heme Bilirubin diglucuronide in bile H2O Urobilinogens & Stercobilinogens

28 Clinical aspect of heme metabolism
Biosynthesis: Porphyrias Bilirubin metabolism: hyperbilirubinemia -Bilirubin is potentially toxic waste product of heme catabolism eliminated by transporting to liver bound to albumin serum, In the liver it is conjugated with glucuronate (to be water soluble), glucuronide conjugate is excreted in bile -High unconjugated bilirubin :bilirubin encephalopathy, also referred to as kernicterus. -Accumulation of bilirubin in the plasma and tissues results in jaundice

29 Porphyria Champe PC, et.al., p.278, 2005

30 Clinical aspect of heme metabolism

31 Clinical aspect of heme metabolism
Crigler-Naijar syndrome Gilbert syndrome **Neonatal jaundice (transient): Phototherapy unconjugated hyperbilirubinemia 1. Hemolytic jaundice 2. Obstructive jaundice 3. Hepatocellular jaundice

32 References 1 Bhagavan, N.V. Medical Biochemistry, 4th ed., (2002) Harcourt/Academic Press, San Diego, pp , Campbell, P.N., and Smith, A.D., Biochemistry Illustrated, 4th ed., (2000) Churchill Livingstone, Edinburgh, pp Champe, P. C., Harvey, R. A., and Ferrier, D. R. (Eds): Amino acids: disposal of nitrogen. In Lippincott's Illustrates Review: Biochemistry, 3rd ed., (2005) Lippincott William and Wilkins, Philadelphia, pp Champe, P. C., Harvey, R. A., and Ferrier, D. R. (Eds): Amino acids degradation and synthesis. In Lippincott's Illustrates Review: Biochemistry, 3rd ed., (2005) Lippincott William and Wilkins, Philadelphia, pp Champe, P. C., Harvey, R. A., and Ferrier, D. R. (Eds): Conversion of amino acids to specilized products. In Lippincott's Illustrates Review: Biochemistry, 3rd ed., (2005) Lippincott William and Wilkins, Philadelphia, pp

33 References 2 Davidson, V. L., Protein and Amino Acid Degradation, In Davidson, V. L. and Sittman, D. B. (eds.)Biochemistry, 4th ed., (1999) Lippincott Williams & Wilkins, Philadelphia, Davidson, V. L., Biosyntesis of Amino Acids and Amino Acid-Derived Compounds, In Davidson, V. L. and Sittman, D. B. (eds.)Biochemistry, 4th ed., (1999) Lippincott Williams & Wilkins, Philadelphia, Davis, R.H., Morris, D.R., and Coffino, P., Sequestered end products and enzyme regulation: the case of ornithine decarboxylase. Microbial. Rev. 56: (1992). Hankey G.J., Eikelboom J.W., Ho W.K., and van Bockxmeer F.M., Clinical usefulness of plasma homocysteine in vascular disease. Med. J. Aust. 20;181(6): (2004). Garrett, R.H., and Grisham, C.M., Principles of Biochemistry with a Human Focus (2002) Harcourt College Publishers, Orlando, pp King, M.W, and Marchesini S., Heme and Porphyrin Metabolism Available at: Accessed January 19, 2005.

34 References 3 Marks, D. B., Marks, A. D., and Smith, C. M., Basic Medical Biochemistry, A Clinical Approach (1996) Williams & Wilkins, Pennsylvania, pp Murray, R. K., Granner, D. K., Mayes, P. A., and Rodwell, V. W. (Eds): Biosynthesis of the nutritionally nonessential amino acids. In Harper's Biochemistry, 24th ed., (1996) Appleton &Lange, Connecticut, pp Murray, R. K., Granner, D. K., Mayes, P. A., and Rodwell, V. W. (Eds): Catabolism of carbon skeletons of amino acids. In Harper's Biochemistry, 24th ed., (1996) Appleton &Lange, Connecticut, pp Murray, R. K., Granner, D. K., Mayes, P. A., and Rodwell, V. W. (Eds): Conversion of amino acids to specialized products. In Harper's Biochemistry, 24th ed., (1996) Appleton &Lange, Connecticut, pp Murray, R. K., Granner, D. K., Mayes, P. A., and Rodwell, V. W. (Eds): Porphyrins and bile pigments. In Harper's Biochemistry, 24th ed., (1996) Appleton &Lange, Connecticut, pp

35 References 4 Murray, R. K., Granner, D. K., Mayes, P. A., and Rodwell, V. W. (Eds): Catabolism of protein and amino acid nitrogen. In Harper's Illustrated Biochemistry, 26th ed., (2003) McGraw Hill, New Delhi, pp Murray, R. K., Granner, D. K., Mayes, P. A., and Rodwell, V. W. (Eds): Catabolism of carbon skeletons of amino acids. In Harper's Illustrated Biochemistry, 26th ed., (2003) McGraw Hill, New Delhi, pp Murray, R. K., Granner, D. K., Mayes, P. A., and Rodwell, V. W. (Eds): Conversion of amino acids to specialized products. In Harper's Illustrated Biochemistry, 26th ed., (2003) McGraw Hill, New Delhi, pp Murray, R. K., Granner, D. K., Mayes, P. A., and Rodwell, V. W. (Eds): Porphyrins and bile pigments. In Harper's Illustrated Biochemistry, 26th ed., (2003) McGraw Hill, New Delhi, pp Seiler, N., Thirty years of polyamine-related approaches to cancer therapy. Retrospect and prospect. Part 1. Selective enzyme inhibitors. Curr. Drug Targets (7): (2003).