1. BIOCHEMICAL REGULATION (2) DR SAMEER FATANI

2. Energetics of membrane transport systems the change in free energy when an unchanged molecules Moves from concentration C1 to concentration C2 on the other side of a membrane is given by the following Eq. ΔG’ = 2.3RT log (C2/C1) A facilitated transport system is one in which ΔG’ is negative and the movement of solute occurs spontaneously, without the need for a driving force. When ΔG’ is positive, as would be the case if C2 is larger than C1, coupled input of energy from some source is required for movement of the solute and the process is called active transport. Active transport is driven by either hydrolysis of ATP to ADP or utilization of an electrochemical gradient of Na + or H + across the membrane.

3. CHANNELS AND PORES Channels and pores in membranes function differentialy: Channels and pores are intrinsic membrane proteins and are differentiated on the basis of their degree of specificity for Molecules crossing the membrane. - Channels are selective for specific inorganic cations and anions, -Whereas pores are not selective, permitting organic and inorganic molecules to pass through the membrane. e.g. Na+ channel permits movement of Na+ at rate ten times greater than K+. The mechanisms of opening and closing the channels: Opening and closing of membrane channels involves a conformational change in the channel protein, in turn this conformational change is controlled by the transmembrane Potential (these channels called voltage-gated channels). e.g. in Na+ channel, depolarization of the membrane lead to an opening of the channel. Binding of specific agent, termed an agonist, is another Mechanism to control opening of a channel. e.g. binding of acetylcholine opens the channel in The nicotinic-acetylcholine receptor.

4. Sodium channel Voltage-sensetive Na+ channels mediate rapid increase In intracellular Na+ following depolarization of the plasma Membrane in nerve and muscle cells. There are four repeat homology units in the channel. Each With six transmembrane α helices. One membrane segment has a positively charged amino acid at every third position and may serve as a voltage sensor. A mechanical shift of this region due to a change in the membrane potential may lead to a conformational change in the protein, resulting In the opening of the channel. Nicotinic-Acetylcholine channel (nAChR) The nicotinic-acetylcholine channel (acetylcholine receptor), is An example of a chemically regulated channel, in which binding Of acetylcholine opens the channel and allowing selective Cations to move across the membrane. the nicotinic-acetylcholine receptor is inhibited by several deadly Neurotoxins including d-tubocurarine.

5. PASSIVE MEDIATED TRANSPORT SYSTEMS Passive mediated transport (facilitated diffusion) is a mechanism for translocation of solutes through cell membranes (from higher to lower concentration) without expenditure of metabolic energy. Glucose transport is facilitated: Eight members of superfamily of membrane proteins that mediate D-glucose transport have been reported in mammalian cells, and are expressed in a tissue-specific manner. The glucose transporters are designated as GLUT1, GLUT2, and so on. All have 12 hydrophobic segments considered to be the transmembrane regions. Most are in the plasma membrane where direction of movement of glucose is usually out to in. GLUT2, however, may be responsible for glucose export from liver cells. GLUT5 of sarcolemmal membranes of skeletal muscle transport fructose preferentially. GLUT4 is an insulin-responsive transporter. Several sugar analogs as well as phoretin are competitive inhibitors.

6. Cl- and HCO+ transport system An anion transporter in erythrocytes and kidneys involves the antiport movement of Cl- and HCO3-. This transporter called “the Na+-independent Cl- - HCO- exchanger”. The direction of the flow is reversible and depends on the concentration gradients of the ions across the membrane. The transporter is important in adjusting the erythrocyte HCO3- concentration in arterial and venous blood. Mitochondria contain a number of transport systems: The inner mitochondrial membrane contains antiport systems for exchange of anions between cytosol and mitochondrial matrix, including: 1- a transporter for exchange of ADP and ATP, 2- a symport transporter for phosphate and H+, 3- a dicarboxylate carrier that catalyzes an exchange of malate for phosphate, and 4- a translocator for exchange of aspartate and glutamate. These transporters mediate passive exchange of metabolites down their concentration gradient.

7. ACTIVE MEDIATED TRANSPORT SYSTEMS