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RESPIRATORY GAS TRANSPORT Biochemistry Departement Medical Faculty Of Andalas University Padang.

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Presentasi berjudul: "RESPIRATORY GAS TRANSPORT Biochemistry Departement Medical Faculty Of Andalas University Padang."— Transcript presentasi:

1 RESPIRATORY GAS TRANSPORT Biochemistry Departement Medical Faculty Of Andalas University Padang

2 2

3 3 Oxygen Transport

4 Total Body Oxygen Stores Oxygen in the Lung (~500 ml O 2 ). Oxygen in the Blood (~850 ml O 2 ). Oxygen in the Cells (very little except Mb-bound).

5 5

6 At the Lung Level

7 At the Tissue Level

8 Oxygen Is Carried in Blood in 2 Forms Bound to hemoglobin in red blood cells. Dissolved in plasma. Normally insignificant.

9 9 Hemoglobin Each “heme” molecule is capable of binding with 1 O 2 molecule and each “globin” molecule is capable of binding with 1 CO 2 molecule. So, each molecule of Hb can bind to either 4 molecules of O 2 and 1 molecule of CO ml of blood has about 15 gm of Hb, at Hct = 0.45

10 10 Binding of O 2 to 4 heme sites given by: Equilibrium constants for different reactions different Binding of first O 2 relatively low affinity 2nd, 3rd and 4th - much higher affinity Equilibrium constants for different reactions different Binding of first O 2 relatively low affinity 2nd, 3rd and 4th - much higher affinity

11 11 Oxygen as Oxyhemoglobin Each gram of Hb can store about 1.34 ml of O 2 : 1 L of blood (150 gm of Hb) can store about 208 ml of O 2  Oxygen Capacity of Hb. With normal cardiac output, about 1040 ml of O 2 can be carried in blood per minute. (4 times of the metabolic demands).

12 12

13 13

14 O 2 Saturation. Units: percent. Fraction or percentage of all the hemoglobin binding sites that are currently occupied by oxygen.

15 15 Oxygen Saturation of Hb

16 Four (5-6?) Things Change Oxyhemoglobin Affinity 1.Hydrogen Ion Concentration, [H + ] Carbon Dioxide Partial Pressure, PCO 2 Temperature [2,3-DPG] Special Case: Carbon Monoxide Hemoglobin variants

17 17

18 18 Factors Affecting Hb-O 2 Affinity: Summary Hydrogen Ion: –Increased H + (decreased pH) increases H + binding to Hb and reduces O 2 affinity (HbO 2 +H +  HbH + +O 2 ). Carbon Dioxide (Bohr effect): –Increased P CO2 increases CO 2 binding to Hb and reduces O 2 affinity (increased O 2 delivery to tissue). –Increased P CO2 increases H + and reduces O 2 affinity (fixed acid Bohr effect). Temperature and 2,3-DPG (diphosphoglycerate): –Increased temperature and 2,3-DPG reduces O 2 affinity.

19 Effect of CO & Anemia on Hb-O 2 Affinity Normal blood with Hb=15 gm/dl, anemia with Hb=7.5 gm/dl, and normal blood with 50% HbCO (carboxyhemoglobin).

20 Exercise Increase temperature Increased PCO 2 and Decreased pH (acidosis)

21 2,3-DPG 2,3-DPG is a glycolytic intermediate –accumulates to uniquely high levels in RBCs -Increased 2,3-DPGright shift -Decreased 2,3-DPG left shift Increased 2,3-DPG associated with hypoxia.

22 Conditions with Increased 2,3-DPG acclimatization to high altitudes. chronic lung disease; emphysema. anemia. hyperthyroidism. right to left shunt. congenital heart disease. pulmonary vascular disease.

23 Blood Bank Storage CPD (citrate phosphate dextrose) Storage 2,3-DPG depletion O.D.C. left-shifted oxygen Oxygen unloading impaired

24 24 Carbon Dioxide Transport

25 25 At the Tissue Level

26 26 At the Lung Level

27 27 Carbon Dioxide Transport CO 2 is transported in blood in dissolved form, as bicarbonate ions, and as protein-bound carbamino compound. Protein-bound CO 2 (carbamino compounds): Amount of CO 2 stored as carbamino compounds is about 21 ml/L (4% of the total art CO 2 ).

28 28 Carbon Dioxide Transport A majority amount of CO 2 is transported in the form of bicarbonate ions (HCO 3 - ): Amount of CO 2 in HCO 3 - form at P CO2 =40 mmHg is about 420 ml/L (90% of the total arterial CO 2 ).

29 29 Carbon Dioxide Transport Haldane Effect: Increasing O 2 -saturation reduces CO 2 content and shifts the CO 2 dissociation curve to right. This is because, increasing P O2 leads to : –Decrease in the formation of carbamino compound. –Release of H+ ions from the hemoglobin and resulting in dehydration of HCO 3 -.

30 30 Carbon Dioxide Dissociation Curve CO2 O2 2 2 Over the normal physiological range (P CO2 = 30 to 55 mmHg and P O2 = 40 to 100 mmHg), the CO 2 equilibrium curve is nearly linear. But, O 2 equilibrium curve is highly nonlinear.

31

32 Bicarbonate in RBCs. Carbonic anhydrase is present in RBCs CO 2 forms carbonic acid which dissociates to H + and HCO 3 - Released H + is buffered by histidine residues (imidazole group) Percent of the total PaCO 2 : 70%

33 Carbamino Compounds in RBCs. Approximately 30% of RBC contents is Hb CO 2 forms carbamino hemoglobin Released H + is buffered by histidine residues (imidazole group) Percent of the total PaCO 2 : 23 %

34 CO 2 Formation in Plasma Carbamino compounds – CO 2 binds the amine groups of plasma proteins to form carbamino compounds.

35 35

36 36

37 Chloride Shift (Hamburger Shift) Newly formed HCO 3 - passes out of RBC Cl - diffuses into RBC to maintain electroneutrality –Chloride shift is rapid –Complete before the RBCs exit capillary

38 38 Tissue-Gas Exchange: Summary Gas exchange processes in the peripheral organs are essentially opposite those in the lungs. O 2 is released from the capillary blood to the tissues and diffuses to the mitochondria where O 2 is converted to CO 2 and energy (ATP) through cellular metabolism. CO 2 diffuses from the tissues to the blood stream and is transported to the lungs for elimination. The exchange of O 2 and CO 2 in the blood-tissue exchange unit depends on P O2, P CO2, and also on O 2 and CO 2 saturation curves.

39 39 Gas Transport in Cell

40 40

41 41 Dilakukan oleh: 1. isositrat dehidrogenase 2. α-ketoglutarat dehidrogenase Pelepasan CO 2 tidak mengkonsumsi oksaloasetat. Pelepasan CO 2

42 42 Siklus ATP/ADP Berperan untuk menghubungkan proses- proses yg menghasilkan P-berenergi-tinggi dgn proses yg menggunakan P-berenergi- tinggi. ATP dikonsumsi & dibentuk kembali secara kontinu. Depot ATP/ADP sangat kecil, sehingga hanya cukup untuk mempertahankan jaringan aktif dlm waktu beberapa detik saja.

43 43 Siklus ATP/ADP ATP CO 2 Pernapasan: Penggunaan energi: pembentukan energi - biosintesis makro- dari; - karbohidrat molekul - lemak - kontraksi otot - protein - transpor ion aktif - termogenesis O 2 ADP + Pi

44 44 Fosforilasi Oksidatif Adalah sistem dalam mitokondria yang memasangkan respirasi dengan proses pembentukan intermediat berenergi tinggi, ATP. Sistem ini memungkinkan organisme aerob menangkap energi bebas dari substrat respiratorik dalam jumlah lebih besar dibanding organisme anaerob.

45 45 Peran Rantai Respirasi asam lemak +  -oksidasi gliserol ATP O 2 glukosa Asetil KoA SAS 2H H 2 O rantai respirasi Asam amino ADP mitokondria

46 46

47 47 Produk ATP pada Fosforilasi Oksidatif Berdasarkan hipotesis kimiosmotik dari Mitchell yaitu; rantai bekerja --> proton dipompa keluar dari membran dlm mitokondria --> pH antar membran turun --> proton balik ke dalam matrik lewat tonjolan ATP-sintase--> fosforilasi ADP menjadi ATP.

48 48 Produk ATP pada Fosforilasi Oksidatif Diperkirakan satu ATP disintesis setiap dua proton melewati tonjolan tsb. Hasilnya ialah; - 3 mol. ATP utk oksidasi 1 mol. NADH - 2 mol. ATP utk oksidasi 1 mol. FADH 2 Laju fosforilasi oksidatif dikendalikan oleh; NADH, oksigen, ADP

49 49 Resources BIOEN 589: Integrative Physiology. Download 24 jan 05. Kennelly, PJ., Rodwell, V W. Proteins: Myoglobin & Hemoglobin. In: Harper’s Illustrated Biochemistry. 27th Ed Miliefsky, M. Respiratory System Ch.23. Download 24 Nov 10. Sheardown, H. Blood Biochemistry. McMaster University. Download 20 Mei 07. Irvin, CG. Respiratory Physiology. Lecture 4A CO2 Transport. In: MEDICAL PHYSIOLOGY 30. Download 22 Jun 09. Marks, DB., Marks, AD., Smith CM. Basic medical biochemistry: a clinical approach Dalam: B.U. Pendit, penerjemah. Biokimia Kedokteran Dasar: Sebuah Pendekatan Klinis. Eds. J. Suyono., V. Sadikin., L.I. Mandera. Jakarta: EGC, 2000 R.K. Murray, D.K. Granner, P.A. Mayes, V.W. Rodwell Harper’s Biochemistry. 27th ed. McGraw-Hill Companies, New York


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