TRANSPORT ACROSS CELL MEMBRANES

TRANSPORT ACROSS CELL MEMBRANES

Introduction

The composition and volume of ICF is kept constant and separate from ECF. The cell membrane is responsible for the maintenance of the intracellular composition through its selective permeability participation in the transport of specific substances. The lipids and proteins of the cell membrane play important roles in this regard. Substances can be transported down an electrochemical gradient (downhill) or against an electrochemical gradient (uphill). While water may pass easily through the cell membranes, water-soluble substances (e.g. electrolytes, charged particles, large uncharged polar molecules such as glucose and amino acids) do not easily pass through the cell membrane.

Thus, these substances can pass through the following, through water-filled channels of integral proteins or by carrier proteins in the cell membrane. Protein channels permit only specific ions to pass through it, e.g. sodium channels, potassium channels, calcium channels. Proteins channels May be continuously open (ungated channels), or open and close when required (gated channels).

Gated channels

i. Mechanical gating

· These channels open by some mechanical factors. For example, in the pressure receptors (Pacinian corpuscles) and receptor cells (hair cells) for hearing in the internal ear (cochlea and vestibular apparatus).

ii. Voltage gating

· These channels open whenever there is a change in membrane potential; e.g. Na+ channels in nerves and muscles.

iii. Ligand gating

· Many ion channels open or close in response to binding a small signalling molecule or "ligand", e.g. hormones and neurotransmitters.

Types of carrier proteins

Three different types of carrier proteins exist:

a. Uniport carriers transport only one substance.

b. Symport carriers transport two or more molecules from one side of the membrane to the other, i.e. in the same direction

c. Antiport carriers transport two or more molecules substances in opposite directions. Substances transported in opposite directions by one carrier are said to be counter-transported, e.g. Na+-K+ pump

Features of carrier-mediated transport

Carrier-mediated Transport

a. Saturation kinetics: Since the number of carrier protein is limited, the rate of transport can reach a maximum velocity known as transport maximum (Tm) which cannot be exceeded by increasing the concentration of the substance, because all the available binding sites have been occupied.

b. Stereospecificity: The binding sites for solutes on transport proteins are stereospecific. For example, the transporter for glucose in the renal proximal tubule recognizes and transports the natural isomer D-glucose, but it does not recognize and transport the unnatural isomer L-glucose.

c. Competitive inhibition: Though carrier proteins are usually specific for the molecules they transport, the presence of molecules with structure like that of the molecule being transported can lead to competitive inhibition of the transport, e.g. D-glucose and D-galactose. Thus, D-galactose occupies some of the binding sites for D-glucose making them unavailable for D-glucose.

5.6 Basic mechanisms of transport

There are two basic types of mechanisms involved in the transport of substances across the cell membrane.

i. Passive transport

ii. Active transport

Mechanisms of transport

PASSIVE TRANSPORT ACROSS THE CELL MEMBRANE

Passive transport describes the movement of substances down a concentration gradient or electrical gradient or both (electrochemical gradient). It is also known as downhill movement. It does not require metabolic energy and is thus not susceptible to metabolic poisons. Passive transport mechanisms across cell membranes are: a] simple diffusion, b] facilitated diffusion, c] osmosis.

Simple diffusion

Simple diffusion, or diffusion, is the net movement of substances from an area of higher concentration to an area of lower concentration. This is due to the random and constant motion characteristic of all molecules, (atoms or ions) and is independent from the motion of other molecules. Since, at any one time, some molecules may be moving against the gradient and some molecules may be moving down the gradient, although the motion is random, the word "net" is used to indicate the overall, eventual result of the movement. Because of diffusion molecules reach an equilibrium where they are evenly spread out. This is when there is no net movement of molecules from either side. Simple diffusion is the only form of transport that is not carrier-mediated.

Examples include O2 (non-polar, so diffuses quickly), CO2 (polar, but very small), and water (polar, but also very small, so diffuses quickly).

Factors affecting rate of diffusion

A. Properties of the substance

i. The steepness of the concentration gradient. The bigger the difference between the two sides of the membrane the quicker the rate of diffusion.

ii. Temperature. Higher temperatures give molecules or ions more kinetic energy. Molecules move around faster, so diffusion is faster.

iii. Permeability of the molecule. This is determined by a) lipid solubility - for lipid soluble substances permeability is proportional to their lipid solubility; b) molecular size -large molecules need more energy to get them to move so they tend to diffuse more slowly; c) polarity or presence of charge on the molecule - non-polar molecules diffuse more easily than polar molecules because they are soluble in the non-polar phospholipid tails.

B. Properties of the membrane

i. The surface area. The greater the available surface area the faster the diffusion can take place. This is because the more molecules or ions can cross the membrane at any one moment.

ii. Thickness of the cell membrane. Rate of diffusion is inversely proportional to the thickness of the cell membrane. If the cell membrane is thick, the diffusion of substances across it is very slow.

Modified Fick’s law of diffusion

· the rate of diffusion of a substance across any membrane (j)

is directly proportional to

· the concentration difference (C2-C1) across the membrane,

· the surface area (A) of the membrane

· the solubility of the substance (S)

AND

Inversely proportional to

· the thickness (t) of the membrane

· Square root of the molecular weight of the substance ().

· J = A x (C2 - C1) x (S) / t x

· This is modified from the Fick's law of diffusion

FACILITATED (OR CARRIER-MEDIATED) DIFFUSION

Facilitated diffusion (FD) is the diffusion of solutes through channel proteins in the plasma membrane. Large polar molecules such as glucose and amino acids cannot diffuse across the phospholipid bilayer. These molecules pass through protein channels instead. FD is downhill, and does not require energy. It is different from simple diffusion in the following ways:

i. It is carrier-mediated;

ii. It exhibits saturation kinetics;

iii. It exhibits competitive inhibition.

Note that in all cases of facilitated diffusion through channels, the channels are selective; that is, the structure of the protein admits only certain types of molecules through. For example: The plasma membrane of human red blood cells contains transmembrane proteins that permit the diffusion of glucose from the blood into the cell. Glucose carriers, sodium ions, and chloride ions channel are examples

Osmosis

Osmosis is the diffusion of water molecules across a selectively permeable membrane, from a region of higher concentration (higher water activity) to a region of lower concentration (lower water activity). OR, the net flux of water from a solution of lower solute concentration to that of higher solute concentration is known as osmosis.

Osmotic effectiveness of a substance: A substance can maintain a stable osmotic pressure if it is effectively confined to one side of the membrane, e.g. plasma proteins.

Osmotic pressure: If the membrane is impermeable to a solute, osmotic flow of water will continue into the side containing the solute until either the membrane bursts (in the case of water entering cells), or some hydrostatic pressure prevents further osmotic flow. The amount of hydrostatic pressure necessary to prevent osmotic flow of water is known as osmotic pressure of the solution.

Tonicity: Tonicity is the effective osmolality (i.e. osmolality that will cause water to move from one compartment to another) and is equal to the sum of the concentrations of the solutes, which have the capacity to exert an osmotic force across the membrane.

Hypotonic solutions: When two solutions (separated by a semipermeable membrane) have different effective osmotic pressures, the one with the lower effective osmotic pressure is hypotonic. Hypotonic solutions are, thus, those with less solute (higher water concentration).

Hypertonic solutions are those in which more solute (and hence lower water concentration) is present.

Isotonic solutions have equal (iso-) concentrations of solutes. When red blood cells are placed in a 0.9% salt solution, they neither gain nor lose water by osmosis. Such a solution is said to be isotonic. The extracellular fluid (ECF) of mammalian cells is isotonic to their cytoplasm.

Diffusion of Water across Cell Membranes

· Water can diffuse through the lipid bilayers of the cell membrane; but diffusion is not sufficiently rapid for many physiological processes.

· To accommodate these needs, a family of membrane channel proteins for rapid transport of water are found in cell membranes.

· Aquaporins or Water Channels

· Aquaporins are a class of integral membrane channel proteins that form pores in the membrane of biological cells and selectively conduct water molecules in and out of the cell, while preventing the passage of ions and other solutes.

· They are each composed of four (typically) identical subunit proteins.

· Water molecules traverse the narrowest portion of the channel single file.

· increases the permeability to water by as much as ten-fold.

· Genetic defects involving aquaporin genes have been associated with several human diseases.

ACTIVE TRANSPORT ACROSS THE CELL MEMBRANE

Active transport is the movement of solutes against chemical, or electrical or electrochemical gradient. It requires the expenditure of metabolic energy, usually in the form of ATP, and is usually carrier-mediated.

Characteristics of active transport

i. Uphill transport.

ii. Requires metabolic energy.

iii. Exhibits saturation kinetics.

iv. Carrier-mediated active transport (requires transmembrane protein (usually a complex of them) called transport proteins or transporters, and

Active transport may be primary or secondary.

Primary active transport

Primary active transport requires a direct input of metabolic energy. Some transporters bind ATP directly and use the energy of its hydrolysis to drive active transport. These transport proteins function as protein pumps one ion pumps, e.g. Na+-K+ pump (Na+-K+ ATPase).

Protein Pumps

· Transport proteins in the plasma membrane transfer ions such as Na+, K+, Cl-, Mg3+ and Ca2+ H+.

· The protein binds to a molecule of the substance to be transported on one side of the membrane, then it uses the released energy (ATP) to change its shape, and releases it on the other side.

· The protein pumps are specific; there is a different pump for each molecule to be transported.

· Protein pumps are catalysts in the splitting of ATP → ADP + phosphate, so they are called ATPase enzymes.

The Na+-K+ pump (or Na+/K+ ATPase)

The Na+-K+ pump (also called the Na+-K+ATPase enzyme) actively moves sodium out of the cell and potassium into the cell. These pumps are found in the membrane of virtually every cell, and are essential in transmission of nerve impulses and in muscular contractions.

The cytosol of animal cells more K+ than ECF while there is more concentration of sodium ions (Na+) in the ECF. These concentration gradients are established by the active transport of both ions. And the same transporter (the Na+/K+ ATPase), does both jobs. It uses the energy from the hydrolysis of ATP to

· actively transport 3 Na+ ions out of the cell

· for each 2 K+ ions pumped into the cell.

The crucial roles of the Na+/K+ ATPase are reflected in the fact that almost one-third of all the energy generated by the mitochondria in animal cells is used just to run this pump.

Secondary Active Transport

Secondary active transport utilizes an indirect input of metabolic energy. It uses the downhill flow of an ion to pump some other molecule or ion against its gradient. The driving ion is usually sodium (Na+) with its gradient established by the Na+/K+ ATPase.

In symport pumps, the driving ion (Na+) and the pumped molecule pass through the membrane pump in the same direction.

Examples:

· The Na+/glucose transporter. This transmembrane protein allows sodium ions and glucose to enter the cell together. The sodium ions flow down their concentration gradient while the glucose molecules are pumped up theirs. Later the sodium is pumped back out of the cell by the Na+/K+ ATPase, e.g. intestine and kidney tubules.

In antiport pumps, the driving ion (again, usually sodium) diffuses through the pump in one direction providing the energy for the active transport of some other molecule or ion in the opposite direction. Example: Ca2+ ions are pumped out of cells by sodium-driven antiport pumps. Other e.g. Na+-H+ antiporter, Na+-K+ antiporter in the renal tubules, Hco3—Cl- exchanger.

Bulk Transport/Vesicular transport

Vesicles and vacuoles that fuse with the cell membrane may be utilized to release or transport chemicals out of the cell or to allow them to enter a cell. These vesicles or other bodies in the cytoplasm move macromolecules or large particles across the plasma membrane.

Types of BULK transport include:

Exocytosis, which describes the process of vesicles fusing with the plasma membrane and releasing their contents to the outside of the cell. This process is common when a cell produces substances for export.

Exocytosis is used for the following purposes:

· Release enzymes, hormones, proteins, and glucose to be used in other parts of the body

· Neurotransmitters (in the case of neurons)

· Communicate defense measures against a disease

· Expel cellular waste

Endocytosis, which describes the capture of a substance outside the cell when the plasma membrane merges to engulf it. The substance subsequently enters the cytoplasm enclosed in a vesicle.

Endocytosis is used for the following purposes:

· Receive nutrients

· Entry of pathogens

· Cell migration and adhesion

· Signal receptors

Types of endocytosis:

Phagocytosis or cell eating.

Phagocytosis is the cellular process of engulfing solid particles by the cell membrane to form an internal phagosome. The plasma membrane engulfs the solid material, forming a phagocytic vesicle, which fuses with lysosomes for the breakdown of the engulfed particle. The actin molecules of the cytoskeleton are responsible for this engulfment. It involves vesicular internalization of solid particles, such as bacteria, e.g. by phagocytes (white blood cell), acquisition of nutrients for some cells, and in the immune system it is a major mechanism used to remove pathogens and cell debris.

Pinocytosis or cell drinking.

Pinocytosis ("cell-drinking") is a form of endocytosis in which small particles are brought into the cell suspended within small vesicles. Pinocytosis is primarily used for fluids and dissolved substances in the extracellular fluid (ECF), and generates very small vesicles. Pinocytosis is nonspecific in the substances that it transports. The plasma membrane folds inward to form a channel allowing dissolved substances to enter the cell. When the channel is closed, the liquid is encircled within a pinocytic vesicle.

Receptor-mediated endocytosis

This occurs when specific molecules in the fluid surrounding the cell bind to specialized receptors in the plasma membrane. As in pinocytosis, the plasma membrane folds inward and the formation of a vesicle follows. This is made possible by Clathrin molecules which eventually coats the endocytic vesicles. Receptor mediated endocytosis is specific in the molecules it transports. For example, certain hormones can target specific cells by receptor-mediated endocytosis. Also, the absorption of LDL by the liver cells. as well as down regulation of receptors

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