CELL & BIOLOGICAL MEMBRANES Lecture-1 First Year, MBBS

1. Department of Biochemistry CELL & BIOLOGICAL MEMBRANES Lecture-1 First Year, MBBS

2. Learning ObjectivesBy the end of this Session, students shall be able to:1. Describe the Elementary Composition of Human body 2. Discuss the Chemical (biomolecular) composition of human body 3. Explain biomolecules, their composition and significance 4. Describe the composition & functions of different organelles of cell. 5. Illustrate Cell and its Biochemical composition, Importance & functions of carbohydrates, proteins and lipids in membranes 6. Describe various types of transport across cell membrane

3. The human body is composed of a few elements that combine to form a great variety of biomolecules. ELEMENT The simplest kind of matter which can not be split in to two or more simpler substances by chemical reactions. COMPOSITION OF THE BODY & MAJOR CLASSES OF MOLECULES

4. ELEMENTARY COMPOSITION OF THE HUMAN BODY (DRY WEIGHT BASIS)

5. Carbon, Oxygen, Hydrogen & Nitrogen: Major components of most biomolecules. Phosphate: Component of nucleic acid & many other molecules. Calcium: Component of bones & teeth and also important in regulation of nerve muscle function.

6. CHIEF COMPONENTS: Carbohydrates Proteins Fats Water Minerals CHEMICAL(biomolecular) COMPOSITION OF HUMAN BODY

7. NORMAL CHEMICAL COMPOSITION FOR A MAN WEIGHING 65 kg

8. Water contributes the major component, although its amount varies widely among different tissues. Its polar nature & ability to form hydrogen bonds render water ideally suited for its function as the solvent of the body.

9. Molecules produced by a living cell such as proteins, carbohydrates or lipids. The major complex biomolecules found in the cells & tissues of humans: DNA (Deoxyribonucleic acid) RNA (Ribonucleic acid) Proteins Carbohydrates Lipids BIOMOLECULES

10. The complex biomolecules are constructed from simple biomolecules.

11. DNA, RNA, proteins, and carbohydrates are referred to as biopolymers because they are composed of repeating units of their building blocks (monomers). Lipids are not generally biopolymers, not all lipids have fatty acids as building blocks.

13. The cell is the basic unit of biology. It was established as fundamental unit of biologic activity by Schleiden & Schwann. CELL

14. PRO-Before, KARYON-Nucleus Prokaryotic cells lack a nucleus EU-True, KARYON-Nucleus Eukaryotic cells have a nucleus NUCLEUS: A complex membrane bound structure that contains genetic information in the form of chromosomes, whose principle constituent is DNA. Major types of cellPROKARYOTIC & EUKARYOTIC CELLS

15. COMPARISON

17. The human body contains about 200distincttypes of cells. This great variation reflects the variety of functions that cell can perform. However, cells are also amazingly similar they are self contained units surrounded by a membrane that separates them from their environment & they are all composed of same types of molecules. Diversity: A Remarkable Feature of Cells

18. CELL MEMBRANE

19. Membranes have a Trilaminar appearance under Electron microscope Thickness of membrane – 5-8 nm Membranes are flexible (amoeboid movements) Membranes are SELF-SEALING (exocytosis, endocytosis, cell division) Membranes are dynamic – constant turnover of proteins & lipids Membranes are selectively permeable to polar solutes Membranes possess the ability to undergo fusion with another membrane without loosing its integrity FEATURES OF MEMBRANES

20. The cell membrane (also called the plasma membrane), which envelops the cell, is a thin, pliable, elastic structure only 7.5-10 nm. Molecular components/constituents: Proteins Polar lipids Carbohydrates CELL MEMBRANE

22. PROTEINS & LIPIDS: Plasma membrane is composed almost entirely of proteins & lipids – their relative proportion vary with the type of membrane e.g., certain neurons have myelin sheath – rich in lipids while inner mitochondrial membrane is very rich in proteins. Plasma membrane of RBCs has about 20 major types of proteins as well as dozen of minor proteins. Many of these are transporters each moving specific solutes across the membrane. MOLECULAR COMPONENTS

23. CARBOHYDRATES: No free CHO in the plasma membrane. CHOs are present as part of glycoproteins or glycolipids.

24. The ratio of proteins to lipids in defferent membranes 0.23 1.1 3.2

25. Proteins: 55 ٪ Phospholipids: 25 ٪ Cholesterol: 13 ٪ Other lipids: 04 ٪ Carbohydrates: 03 ٪ The Approximate Composition Of Cell Membrane

26. Lipids are the basic structural component of plasma membrane. TYPES OF LIPIDS: 1. PHOSPHOLIPIDS i. Glycerophospholipids – are most abundant ii. Sphingolipids – common in myelin sheath 2. STEROL Cholesterol LIPIDS

27. Phospholipids have two parts: 1. Polar head group: It is hydrophilic portion that interacts with water at each surface of the bilayer (faces ICF & ECF). 2. Non polar fatty acyl chains – Tail: It is the hydrophobic portion of phospholipid molecules. The hydrophobic portion of phospholipid molecules are repelled by water but are mutually attracted to one another, they have a natural tendency to attach to one another in the middle of the membrane. PHOSPHOLIPIDS

28. The lipid layer in the middle of the membrane is impermeable to water soluble substances, such as ions, glucose & urea. Conversely, fat soluble substances, such as oxygen, CO2 , & alcohol can penetrate this portion of the membrane with ease.

29. PHOSPHOLIPIDS: STRUCTURE Polar head group Apolar, hydrocarbon tails

30. PHOSPHOLIPIDS: STRUCTURE ECF hdrophilic Hydrophilic Hydrophobic Hydrophilic ICF

31. Cholesterol is a very hydrophobic compound (four fused rings, A, B, C, D,& it has 8- carbon, branched hydrocarbon chain attached to C- 17 of the D ring). The only hydrophilic portion is the -OH group attached at C- 3 of the A ring. Cholesterol intercalates among the phospholipids with its -OH group at the aqueous interface & remainder within the leaflet. STEROL – CHOLESTEROL

32. Two types of proteins are found in plasma membrane: Peripheral proteins Integral proteins PROTEINS

33. Peripheral proteins are attached only to one face of membrane and do not penetrate all the way through. Peripheral proteins do not interact directly with the hydrophobic cores of the phospholipids in the bilayer and thus do not require use of detergents for their release. They are weakly bound to the hydrophilic regions of specific integral proteins and head groups of phospholipids and can be released from them by treatment with salt solutions of high ionic strength. PERIPHERAL PROTEINS

34. Integral membrane proteins span the full thickness of bilayer and protrude from both inner and outer membrane surfaces. As integral membrane proteins interact extensively with the phospholipids, they require the use of detergents for their solubilization. Integral membrane proteins are very firmly associated with the membrane- due to hydrophobic interactions between membrane lipids and hydrophobic domains of the proteins. INTEGRAL PROTEINS

35. No free CHOs in membrane Occur almost invariably in combination with proteins or lipids in the form of glycoproteins or glycolipids. In fact, most of the integral membrane proteins are glycoproteins & about 1/10th of the membrane lipid molecules are glycolipids. One or several oligosaccharides are joined covalently to proteins. CARBOHYDRATES (The Cell Glycocalyx)

36. The glycoportions of these molecules almost invariably protrudes to the outside of the cell, dangling outward from the cell surface. Many other CHO compounds called PROTEOGLYCANS which are mainly CHO substances bound to small protein cores – are loosely attached to the outer surface of the cell as well. Thus the entire outside surface of the cell often has a loose CHO coat is called the GLYCOCALYX.

37. Membranes define the external boundaries of cells & regulate the molecular traffic across that boundary Membranes divide the internal space in to discrete compartments to regulate processes & compounds in eukaryotic cells Organize complex reaction sequences e.g. electron transport chain Involved in energy conservation FUNCTIONS OF MEMBRANE

38. Membranes have transporters & ion channels Involved in cell to cell communication Membranes possess receptors for hormones, neurotransmitters & growth factors

40. Students are welcome to ask related questions Question /Answer Session

41. Thank You

42. MEMBRANES HAVE ASYMMETRIC STRUCTURE Proteins are inserted in an asymmetric fashion. Oligosaccharide chains always project towards exterior. Lipid components are also distributed in an asymmetric fashion. e.g., in membrane of RBCs, outer leaflet of bilayer contains mostly phosphatidylcholine and sphingolipids, whereas inner leaflet contains phosphatidylethanolamine and phosphatidylserine. Moreover, cholesterol is generally present in larger amounts on the outside than on the inside. MEMBRANE ASYMMETRY

43. Membranes have asymmetric • inside and outside faces. • The membrane’s synthesis • and modification by the ER • determines this • asymmetric distribution of • lipids, proteins and • carbohydrates.

44. 1. Phospholipids form bilayer. 2. Certain lipids determine fluidity of plasma membrane: Cholesterol Saturated and unsaturated fatty acids (components of phospholipids) 3. Provide permeability barrier for water soluble molecules. FUNCTIONS OF MEMBRANE LIPIDS

45. 4. Provide a hydrophobic region in which part or major part of membrane proteins are embedded. 5. Provide site for attachment of : Peripheral proteins (electrostatic interactions) Oligosaccharide chains

46. Many of them have negative electrical charge which gives most cells an overall negative surface charge that repels other negative objects. The glycocalyx of some cells attaches to the glycocalyx of other cells, thus attaching cells to one another. CHOs play an important role in cell-cell recognition. Many of the CHOs act as receptor substance for binding hormones. FUNCTIONS OF MEMBRANE CHOs

47. Cell-cell recognition: The ability of a cell to distinguish one type of neighboring cell from another. • Cell-cell recognition is crucial in the functioning of an organism. It is the basis for: • Sorting of cells into tissues and organs in an animal embryo’s cell. • Rejection of foreign cells by the immune system. Membrane carbohydrates are important for cell-cell recognition

48. The way cells recognize other cells is probably by keying on surface molecules (markers) Markers: Surface molecules found on the external surface of the plasma membrane that distinguish one cell from another.

49. Many of the integral proteins provide structural channels (or pores) through which water molecules & water soluble substances, especially ions, can diffuse b/w the ECF & ICF. These protein channel also have selective properties that allow preferential diffusion of some substances over others e.g. Aquaporins. Other integral proteins act as carrier proteins for transporting substances that otherwise could not penetrate the lipid bilayer. FUNCTIONS OF MEMBRANE PROTEINS: Integral Membrane Proteins

50. Sometimes these even transport substances in the direction opposite to their natural direction of diffusion, which is called ‘active transport’. Glucose transporters (GLUT 1-5) are integral membrane proteins that transport glucose. 3. Some integral membrane proteins act as enzymes e.g. Na+ - K+ ATPase Adenylylcyclase Guanylylcyclase