Transport mechanisms: Active and passive, Ligands and Ionophores - Gafacom (For health. For knowledge)

Transport mechanisms: Active and passive, Ligands and Ionophores


An important function of the membrane is to withhold unwanted molecules, while permitting entry of molecules necessary for cellular metabolism

The permeability of substances across cell membrane is dependent on their solubility in lipids and not on their molecular size. Water soluble compounds are generally impermeable and require carrier mediated transport. An important function of the membrane is to withhold unwanted molecules, while permitting entry of molecules necessary for cellular metabolism








Transport mechanisms are classified into

1. Passive transport

1-A. Simple diffusion 1-B. Facilitated diffusion. 1-C. Ion channels are specialized carrier systems. They allow passage of molecules in accordance with the concentration gradient.

2. Active transport

3. Pumps can drive molecules against the gradient using energy.


Simple Diffusion Solutes and gases enter into the cells passively. 

They are driven by the concentration gradient. The rate of entry is proportional to the solubility of thatsolute in the hydrophobic core of the membrane. Simple diffusion occurs from higher to lower concentration. This does not require any energy. However, it is a very slow process.


Facilitated Diffusion. 

This is a carrier mediated process. Important features of facilitated diffusion are: a. The carrier mechanism could be saturated which is similar to the Vmax of enzymes. b. Structurally similar solutes can competitively inhibit the entry of the solutes. c. Facilitated diffusion can operate bidirectional. d. This mechanism does not require energy but the rate of transport is more rapid than simple diffusion process. e. The carrier molecules can exist in two conformations, Ping and Pong states.

In the pong-state, the active sites are exposed to the exterior, when the solutes bind to the specific sites. Then there is a conformational change. In the ping state, the active sites are facing the interior of the cell, where the concentration of the solute is minimal. This will cause the release of the solute molecules and the protein molecule reverts to the pong state. By this mechanism the inward flow is facilitated, but the outward flow is inhibited. Hormones regulate the number of carrier molecules. For example, glucose transport across membrane is by facilitated diffusion involving a family of glucose transporters


Aquaporins

They are water channels. They are a family of membrane channel proteins that serve as selective pores through which water crosses the plasma membranes of cells. They form tetramers in the cell membrane, and facilitate the transport of water They control the water content of cells. Agre and MacKinnon were awarded Nobel prize for chemistry in 2003 for their contributions on aquaporins and water channels. Diseases such as nephrogenic diabetes insipidus is due to impaired function of these channels

Channelopathies are a group of disorders that result from abnormalities in the proteins forming the ion pores or channels. A few examples are cystic fibrosis (chloride channel), Liddle's syndrome (sodium channel) and periodic paralysis (potassium channel)

Ion Channels Membranes have special devices called ion channels. 

Ion channels are trans membrane proteins that allow the selective entry ofvarious ions.  These channels are for quick transport of electrolytes such as Ca++, K+, Na+ and Cl--. These are selective ion conductive pores. Ion channels are specialized protein molecules that span the membranes.


The channels generally remain closed, but in response to stimulus, they open allowing rapid flux of ions down the gradient. This may be compared to opening of the gate of a cinema house, when people rush to enter in. Hence this regulation is named as "gated". Such ion channels are important for nerve impulse propagation, synaptic transmission and secretion of biologically active substances from the cells. Ion channels are different from ion transport pumps described below.






Ligand Gated Channels

Ligand gated channels are opened by binding of effectors. The binding of a ligand to a receptor siteon the channel results in the opening (or closing) of the channel. The ligand may be an extracellular signalling molecule or an intracellular messenger.

Acetyl choline receptor is the best example for ligand gated ion channel. It is present in postsynaptic membrane. It is a complex of 5 subunits, consisting of acetyl choline binding site and the ion channel. Acetyl choline released from the presynaptic region binds with the receptors on the postsynaptic region, which triggers opening of the channel and influx of Na+. This generates an action potential in the postsynaptic nerve. The channel opens only for a millisecond, because the acetyl choline is rapidly degraded by acetyl cholinesterase.


Calcium channels

Under appropriate stimuli calcium channels are opened in the sarcoplasmic reticulum membrane, leading to an elevated calcium level in the cytosol of muscle cells. Calcium channel blockers are therefore widely used in the management of hypertension.


Amelogenin, a protein present in enamel of teeth has hydrophobic residues on the outside

A 27 amino acid portion of amelogenin functions as a calcium channel.Phosphorylation of a serine residue of the protein opens the calcium channel, through which calcium ions zoom through and are funnelled to the mineralization front. The amelogenin is used for the formation of calcium hydroxy apatite crystals.


Voltage Gated Channels

Voltage gated channels are opened by membrane depolarization. The channel is usually closed in the ground state. The membrane potential change (voltage difference) switches the ion channel to open, lasting less than 25 milliseconds. In voltage gated channels, the channels open or close in response to changes in membrane potential. They pass from closed through open to inactivated state on depolarization. Once in the inactivated state, a channel cannot re-open until it has been reprimed by repolarization of the membrane.

Voltage gated sodium channels and voltage gated potassium channels are the common examples. These are seen in nerve cells and are involved in the conduction of nerve impulses. Ion channels allow passage of molecules in accordance with the concentration gradient. Ion pumps can transport molecules against the gradient.


Ionophores

They are membrane shuttles for specific ions. They transport antibiotics. Ionophores increase the permeability of membrane to ions by acting as channel formers. The two types of ionophores are; mobile ion carriers (e.g. Valinomycin) and channel formers (e.g. Gramicidin). They are produced by certain microorganisms and are used as antibiotics. When cells of higher organisms are exposed to ionophores, the ion gradient is dissipated. Valinomycin allows potassium to permeate mitochondria and so it dissipates the proton gradient; hence it acts as an uncoupler of electron transport chain




Transport mechanisms: Active and passive, Ligands and Ionophores Transport mechanisms: Active and passive, Ligands and Ionophores Reviewed by gafacom on January 22, 2020 Rating: 5

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