2-interstetial ( between the vessels and the cells), it is part of extracellular and extravascular.

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1 Quick revision: Fluids in the human body divided to: a- Intracellular ( inside the cell).. b- Extracellular (outside the cell), which in turn is divided to : 1-intravascular (inside vessels) 2-interstetial ( between the vessels and the cells), it is part of extracellular and extravascular. *what is the difference between intravascular and interstitial fluids? (intravascular) : there is a high concentration of protein. (interstitial fluid) : there is a low concentration of protein. *Simple diffusion : directly throughout the plasma membrane or throughout channels. Channels are sometimes (opened) active : this increases the permeability of the membrane which leads to more diffusion from one side to another side ( without any limitations). They also could be (closed) inactive. For carriers ( there are some limitations) *mechanisms of transport : 1-passive transport mechanisms ( we finished them in the last 2 lectures) 2-active transport mechanisms ( today's lecture) Active transport mechanisms : 1-primary active transport. 2-secondary active transport. 3-vesicular transport. *what is the difference between primary active transport and secondary active transport? They are classified according to the source of energy used to cause transport; in primary active transport, the energy is derived directly from breakdown of ATP. In secondary active transport, the energy is derived secondarily from energy that has been stored in the form of ionic concentration gradient that was created originally by primary active transport. ( this is a way of conservation of energy). The mechanism of active transport: *the protein complex that is performing the active transport is phpsphorylated by consuming ATP, through a process we call ( phosphorylation) leading to the conformational changes which in turn result in transporting of particles from the low concentration to the high concentration.

2 First: primary active transport: *depends on carrier proteins; which could be named with pumps as well as ATP-dependent. ( these carriers depend on ATP molecules). *types of pumps: 1-Na+ / K+ pump. 2-H+ pump. 3-H+/K+ pump. 4-Ca++ pump Note** some pumps can pump two types of ions. Other pumps can pump only one type of ions. 1)sodium-potassium pump: Outside the cell: there is a high concentration of sodium ions, on the other hand, there is a high concentration of potassium ions inside the cell. the main function: it pumps sodium ions outward through the cell membrane and at the same time pumps potassium ions from the outside to the inside. the carrier protein which response for this action has specific features that are important for the efficient functions of the pump: 1-has 3 sites for sodium binding. 2-has 2 sites for potassium binding. The mechanism : First, 3 sodium ions bind to their sites, stimulating ATP-dependent phospholyration to occur, which leads to conformational changes ( changes in protein's shape) that are responsible for expelling those 3 sodium ions outside the cell. At the same time, 2 potassium ions bind to their sites, stimulating the dephosphorylation to occur, which restores the origin of conformation of the pump protein, releasing the 2 potassium ions inside the cell. After that, the sodium ion sites are ready to bind Na+ again; and the cycle repeats. **assume that this pump is not functioning, what will happen? Osmolarity inside the cell would increase which causes a swelling of the cell. ** what are the functions of this pump? 1-maintaining the sodium and potassium concentration differences across the cell membrane. 2-establishing a negative electrical voltage inside the cell by expelling 3 Na+ outside the cell, and releasing 2 K+ inside the cell. This is why we call this pump ( electrogenic pump).

3 2) hydrogen-potassium pump : It is important in the stomach( where the PH is too low). the stomach has special cells responsible for secreting hydrochloric acid (HCl); which in turn has functions inside stomach ( but we don't have to know these functions). Hydrogen is formed by some secretory cells. Inside the lumen : there is a high concentration of hydrogen ions, but inside the cells there is a low concentration. Hydrogen ions are transported from the low concentration region to the high concentration region. ** the secretion of HCl can be decreased by blocking the pump. 3) calicium pump: In the compartments of ER in some cells, there is a high concentration of calcium ions. ** the function of this pump is to keep the high concentration of calcium ions inside these compartments in the endoplasmic reticulum (ER). *cardiac muscle ( heart muscle) and skeletal muscles: The optimal function of cardiac muscle is to be contracted and relaxed in turns. Cardiac muscle requires extracellular calcium ions for contraction to occur. On the other hand, during relaxation; the calcium ions have to be reduced by pumping them from the cytosol to the ER and extracellular fluid. If calcium ions concentration hasn't be reduced, the function of the heart will be less efficient. *Unlike cardiac muscle; skeletal muscles have no calcium pumps in the plasma membrane, but they have pumps in the ER. Note: Some enzymes, when they are phosphorylated they are considered as active enzymes, once they are dephosphorylated, they become inactive. In contrast, there are some enzymes which are considered as inactive when they are phosphorylated, and they become active when they are dephosphorylated. Second: the secondary active transport: The carriers in this case have 2 sites; one for sodium and the other one for another substance. For the transport to occur, both of sites must be filled, if not, there will be no transport.

4 1-Co- transport ( symport): **when sodium ions are transported out of cells by primary active transport, a large concentration gradient of sodium ions across the cell membrane develops. This gradient represents a stored energy. The excess sodium outside the cell membrane is always attempting to diffuse to the interior ( from the high concentration region to the low concentration region throughout the passive transport). This diffusion energy of sodium can pull other substances ( glucose, amino acid, galactose, dipeptides or tripeptides) along with sodium through the plasma membrane. 2-counter transport ( antiport): ** there are some carriers at the level of the heart responsible for transporting two ions (not one ion and a big particle), these two ions are sodium ion which goes from the high concentration region to the low concentration region inside the cell and calcium ion which goes in the opposite direction. *Co-transport: the sodium and the other substance move in the same direction. *Counter transport: the sodium and the other substance go in the opposite directions. Note** These carriers are designed as channels, but they are not channels, they are carriers. **what are the mechanisms in which Ca++ can be transported from the cytosol of the heart muscle to the outside?? 1-Ca++ pump. 2- counter- transport ( sodium-calcium exchange) *Sodium-dependent carriers: related to the secondary active transport. *ATP-dependent carriers: related to the primary active transport. Some examples of Co-transport : Co-transport of nutrients: *Nutrients are transported from the lumen of the small intestine toward the inside of the absorptive cells. *There is a sodium-potassium pump in the basolateral membrane ( the surface of the plasma membrane that forms its basal and lateral surfaces), but it doesn't exist in the lumenal membrane. In the small intestine: glucose absorption into cells occurs via a Na/glucose co-transporter. Glucose, which is not phosphorylated and highly concentrated inside the cells, is pumped into the cells (from the low concentration to the high concentration) using the energy of the Na gradient ( sodium moves from the high concentration to the low concentration), both of them ( sodium and glucose) moves toward the inside of cells.

5 At the level of liver and muscles: - If there is a glucose molecule inside the cell it will be immediately phosphorylated. - The transport of glucose takes place by facilitated diffusion! - The facilitated diffusion maintains the difference in glucose concentration; that is high concentration outside the cell and low concentration of non-phosphorylated glucose inside the cell. The carriers that are used in the secondary active transport, have 2 binding sites; one for sodium and one for another substance. **these carriers differ from those which are used in the facilitated diffusion. I'm sorry for any mistake. I really tried my best الحاضر ينادينا! الماضي يسأم من ذكرياتنا أحيانا.. والمستقبل يمل من أحالمنا.. ولكن الحاضر وحده تضيق أنفاسه وهو ينادينا : "أنا موجود.. ال تذهبوا بعيدا".. عذرا أيها الحاضر.. ألننا نحاول الهروب منك رغم أنك أنت من تتمسك بنا.. عذرا أيها الماضي.. عذرا أيها المستقبل.. هناك عشق يناديني اسمه " الحاضر"..

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