01.DIFFUSION ACCROSS CELL MEMBRANE PPT.pptx

DIFFUSION ACCROSS CELL MEMBRANE

1. Diffusion

2. Diffusion Diffusion refers to passive transport of molecules from areas of higher concentration to areas of lower concentration. Two subtypes- simple diffusion facilitated diffusion

3. LIPID SOLUBLE O2 Nitrogen CO2 Steroid hormones Weak organic acids & bases LIPID INSOLUBLE Water Urea Non hydrated sodium and potassium ion WATER SOLUBLE Glucose Most amino acids

4. Protein channels have following characteristics- Selective permeability Gating mechanism Voltage gated channel Ligand gated channel or Chemical gating Mechanical gated channel

5. Simple Diffusion- lipid soluble substances All the molecules are at constant random movement ( thermal motion) except at Absolute zero temperature. Physicist call it “heat”. There will be Net diffusion of the solute until the solute concentration between two solutions become equal( Diffusional Equilibrium ). This is called Flux or flow (J). Rate of diffusion α lipid solubility

6. Net movement of the molecules across a permeable membrane where only simple diffusion is occurring is expressed by Fick’s law of diffusion . J= DA ( C1-C2) T J= net rate of diffusion D= diffusion coefficient A= cross-sectional area T= thickness of the movement C1-C2 = concentration gradient

7. Diffusion of Electrolyte If there is a potential difference across the membrane. That potential difference will alter the net rate of diffusion of a charged solute. When a charged solute diffuse down a concentration gradient That diffusion itself generate a potential difference across a membrane called – Diffusion potential .

8. Simple Diffusion- through pores or channels Diffusion of water & other lipid-insoluble molecules through protein channels. Protein channels or pores are transmembrane protein . Pores are called aquaporins. At least 13 different types of aquaporins found in human body . They are highly selective. The rapidity of diffusion is very fast through this channels. More larger molecules < diffusion rate. ( Urea is 20% larger than water molecule & diffusion rate 1000 times less than water).

9. Some channels are always open and some channels are gated channels. Aquaporins have narrow pore that permits water molecules diffuse in a single file. The pore is too narrow to permit passage of any hydrated ions.

10. Selectivity results from characteristics of the channel i.e. its diameter, its shape, nature of electrical charges & chemical bonds along its inside surface. K+ ion larger than Na+ ion but diffusion of K+ is 1000 times more than Na+. So high degree of selectivity cannot be explained by molecular diameter.

11. Lining of selectivity filter are carbonyl oxygen Hydrated K+ ion enter the selectivity filter, interact with carbonyl oxygen Shed most of their bound water molecules Permitting the dehydrated K+ ions to pass through the channels. Diffusion of K+:

12. Inner surface of Na+ channel are lined with amino acids that are strongly negative charged This strong negative charges can pull small dehydrated sodium ions into these channels. Actually pulling the Na+ ions away from their hydrated water molecules Diffusion of Na+:

13. Gating of protein channels Voltage gating :- Na gate (outside) remain closed when inside strong negative charge. Opens when inside membrane loses its negative charge. K gate (inside) opens when inside of the cell membrane becomes positively charged. 2. Chemical/Ligand gating :- Gates open when some other chemical molecules binds with the gate protein. Ligand may internal or external. i.e.- acetylcholine channels. Extracellular ligand- first messenger Intracellular ligand- second messenger( Ca2+,cAMP, G protein) 3. Mechanical gating :- opened by mechanical stretch. Example- Pacinian corpuscles -Hair cells in the organ of corti

14. Na + Channels K+ Channels OUT Ca 2+ Channels Proton Channels (H + ) Anion Channels ( Cl - & HCO 3 - ) OUT

15. When the net driving force is negative, cations will enter the cell and anions will exit.

16. Gap junction channels (also called hemichannels) are formed between two adjacent cells and open to allow passage of ions and small molecules between the cells. The hemichannels are generally hexameric (i.e., consisting of six subunits, or connexins).

17. Facilitated Diffusion- Downhill movement. Carrier protein used so called- Facilitated or Carrier mediated diffusion. Requires no input of metabolic energy. Large water soluble molecules i.e. Glucose , Amino acids diffuse through this process. Maintain saturation kinetics – rate of diffusion approaches a maximum, called V max. Exhibits all the characteristics of carrier- mediated transport : saturation , stereospecificity, competition .

18. The rate of facilitated diffusion is greater than that of passive diffusion at lower solute concentrations. However, at higher solute concentrations the rate of facilitated uptake reaches its Vmax (i.e., the carrier is saturated), whereas the rate of passive diffusion is not limited by a carrier. Vmax can be increased by adding transport proteins to the membrane, which is a key regulatory aspect of the transport process. Glucose transport through membrane protein (GLUT). At least 14 members of GLUT. GLUT 4 activated by Insulin. Increase facilitated diffusion 10-20 fold in insulin sensitive tissue.

19. Nernst Potential:- If an electrical potential is applied across the membrane, the electrical charges of the ions cause them to move through the membrane even though no concentration difference exists to cause movement. Therefore net diffusion occurs from left to right. A concentration difference developed from rt to left. At normal body temp (37 degree C), the electrical difference that will balance a given concentration difference can be determined by Nernst Equation- EMF (in millivolts) = + 61 log C1/C2 _

20. Over 100 years ago, midwives performed an unusual test on the infants they delivered: The midwife would lick the infant’s forehead. A salty taste meant that the child was destined to die of a mysterious disease. Daniel’s (18mts) medical history tells a frightening story of almost constant medical problems since birth: recurring bouts of respiratory infections, digestive ailments, and, for the past six months, a history of weight loss. APPLIED:-

21. Today, a similar “sweat test” will be performed in a major hospital. The name of the mysterious disease- Cystic fibrosis. A culture taken from Daniel’s lungs raised a red flag for cystic fibrosis: The mucus from his airways was unusually thick and dehydrated . In cystic fibrosis, this thick mucus causes life-threatening respiratory congestion and provides a perfect breeding ground for infection causing bacteria.

22. In people with cystic fibrosis, movement of sodium chloride into the lumen of the airways is impaired. Why would failure to move NaCl into the airways cause the secreted mucus to be thick? ANS- If NaCl is secreted into the lumen of the airways, the solute concentration of the airway fluid increases. Water moves into compartments with higher osmolarity.

23. ANS- Chemically gated channels open when a ligand binds to them. CFTRs open when ATP binds to the channel protein. ATP is a chemical ligand, which means CFTRs are chemically gated channel proteins.

24. CFTR and Na+ channels move Cl - and Na+ out of the sweat and back into the body. The duct cells are not permeable to water, so that normal reabsorption of NaCl creates sweat with a low salt content. However, without functioning CFTR channels in the epithelium, salt is not reabsorbed. In cystic fibrosis, salt concentrations in the sweat can be four times the normal amount.

25. Daniel is diagnosed with cystic fibrosis. Now, along with antibiotics to prevent lung infections and therapy to loosen the mucus in his airways, Daniel must begin a regimen of pancreatic enzymes to be taken whenever he eats, for the rest of his life. In cystic fibrosis, thick mucus in the pancreatic ducts blocks the secretion of digestive enzymes into the intestine. Without artificial enzymes, he would starve. Why will Daniel starve if he does not take artificial pancreatic enzymes? ANS- The pancreas secretes mucus and digestive enzymes into ducts that empty into the small intestine. In cystic fibrosis, mucus in the ducts is thick because of lack of Cl - and fluid secretion. This thick mucus blocks the ducts and prevents digestive enzymes from reaching the small intestine.

26. Thank You…..