Cellular Physiology Flashcards
Hyperaldosteronism
Hyperaldosteronism will increase sodium reabsorption and potassium secretion. This will increase the concentration of extracellular sodium. Fluids will flow from intracellular fluid to extracellular fluid due to the concentration gradient differences. Furthermore, sodium retention by the kidneys will increase bicarbonate reabsorption and acid excretion. Oedema is not found in hyperaldosteronism as may be expected.
Equilibrium potential
Equilibrium potential for a single ion system is synonymous with reversal potential. It is defined as the membrane potential at which there is no net inward or outward movement of an ion across the cell membrane. It depends on the ratio of the concentrations of that ion inside and outside the cell. It is the potential that the membrane potential would approach if the membrane became freely permeable to that ion. It would be zero if the concentrations of that ion on each side of the membrane were equal.
Sodium’s equilibrium potential is positive, whereas potassium and chloride have negative equilibrium potentials. In normal circumstances, the resting membrane potential is close to the equilibrium potential of potassium. Increasing the membrane permeability to sodium and potassium will depolarize the membrane. As mentioned above, sodium has a positive equilibrium potential, so increasing its permeability would increase the membrane depolarization to the maximum. If increased sodium permeability is coupled with potassium, it will decrease the effect of sodium on membrane depolarization.
Bicarbonate is mainly an extracellular anion where its concentration ranges from 22-28 mmol/L. The intracellular HCO3- level is 10 mmol/L. It is a major part of the intracellular and extracellular buffer apparatus to maintain the pH. Intracellular bicarbonate ions play an important role in maintaining membrane potential as well.
The Na+ gradient across a nerve cell membrane is used as an energy source for the transport of other ions. It is not the result of the Donnan equilibrium, which is defined as an equilibrium between two solutions separated by a semi-permeable membrane. The sodium gradient is not significantly changed during an action potential. Potassium gradient is the primary determinant of the resting membrane potential. The Na+ gradient is maintained by Na+/K+-ATPase pump.
The bicarbonate ion is mainly an extracellular anion. Its intracellular concentration is less than the extracellular concentration. Sodium, chloride, and calcium ions are also mainly extracellular ions. The intracellular concentration of potassium ions, magnesium ions, cholesterol, and amino acids is higher than the extracellular concentration. The intracellular concentration of proteins is four times higher than the extracellular concentration.
Only small, uncharged molecules can diffuse freely across the cell membrane, for example O2, CO2, and H2O. Larger uncharged polar molecules like glucose, amino acids, and chylomicrons cannot pass freely. Inorganic ions, such as Na+, K+, and Ca++, pass across the cell membrane through ion channels which form open pores to allow their free passage. Small molecules such as glucose and amino acids are transported by carrier proteins. Urea can pass passively across cell membranes. However, due to its low solubility in the lipid bilayer, its transport is accelerated by urea transporters, which transport the urea by facilitated diffusion. Chylomicrons are released from the intestinal cells through a process of exocytosis.
Skeletal muscle
Skeletal muscle is composed of a collection of muscle fibers. Skeletal muscle cells have a peripheral nucleus, use glycogen as their main energy store, and have multiple mitochondria to meet energy needs. Muscle fibers are classified based on their color, metabolism, and fatigability in I, IIa, IIb, or IIx. A skeletal muscle fiber is innervated by only one neuron that causes neuromuscular transmission, resulting in the release of intracellular Ca2+ from the sarcoplasmic reticulum and recruitment and cycling of cross-bridges.
Skeletal muscles originate embryologically through the fusion of individual myoblasts. Hence, these cells are fused and multinucleated forming a syncytium. Myofibril is the basic rod-like unit of a microfiber. Myofibrils contain myofilaments. Under the electron microscope, a repeating sequence of striations is seen. Each sequence constitutes a sarcomere. Each sarcomere is limited by a Z-band. Each sarcomere is supported by two transverse tubules (T tubules).
Calcium storage cell
Extracellular calcium has an inward electrical and concentration gradient because it’s more abundant in the extracellular fluid than the intracellular fluid, and is a strong, positively-charged ion compared to the negatively-charged cells.
Intracellular calcium is stored in the organelles, especially mitochondria and the endoplasmic reticulum. Calcineurin may limit Ca2+ influx through dihydropyridine-sensitive Ca2+ channels in the plasma membrane by dephosphorylating the channel or a closely-associated protein and inactivating it.
Calcium has many effects, such as bone remodeling and neural activity. It has an opposing effect based on its concentration. For example, in a normal concentration, calcium ions play a major part in muscle contraction. However, when the concentration of calcium ions rises above normal (hypercalcemia), muscle contraction can’t occur, causing a person to become hypotonic.
The increase in intracellular calcium ions is the initiating stimulus for smooth muscle contraction. However, its role differs in smooth muscles as compared to skeletal muscles. In skeletal muscles, contraction is initiated when calcium binds to troponin. In smooth muscles, calcium binds to calmodulin, and calcium–calmodulin complex initiates the contraction. The source of activation of calcium ions, mechanism of the force of contraction, source of energy, and nature of contractile protein are the same.
Cell ATP consumption
Protein synthesis 75% of ATP use
Paracrine, autocrine, endocrine, exocrine
Paracrine signalling is a form of cell signalling or cell-to-cell communication in which a cell produces a signal to induce changes in nearby cells, altering the behavior of those cells.
Autocrine signalling is a form of cell signalling in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell.
Endocrine signalling occurs when endocrine cells release hormones that act on distant target cells in the body.
Exocrine signalling occurs when cells secrete signalling molecules into the circulation.
Things that are never incorporated into proteins
Taurine, l dopa, thyroxine, serotonin - never incorporated into proteins
IDL’s
ntermediate-density lipoproteins (IDLs) are VLDLs from which a share of the triglycerides has been removed, so the concentrations of cholesterol and phospholipids are increased. LDLs are especially important in the different stages of phospholipid and cholesterol transport from the liver to the peripheral tissues. The heart has virtually no glycogen reserves. Fatty acids are the heart’s main source of fuel. Adipose tissue lipoprotein lipase activity is high after feeding and low during fasting and stress.
Protein diet and calcium absorption
Researchers have found that a high-protein diet increases intestinal calcium absorption. Alkalosis promotes tetany by causing hypocalcemia. Parathormone indirectly exerts its effect on intestinal calcium absorption via its effects on vitamin D metabolism. 45% of calcium circulates as free calcium, whereas 40% is bound to albumin, and the remaining 15% is bound to organic and inorganic anions. Most of the renal calcium reabsorption takes place in proximal convoluted tubules.
Brown fat
Brown fat is also present and metabolically active in adult humans. It is located between the shoulder blades, surrounding the kidneys, the neck, and supraclavicular area, and along the spinal cord. Upon leaving fat cells, fatty acids ionize strongly in the plasma and the ionic portion combines immediately with albumin molecules of the plasma proteins. While passing through the intestinal epithelial cells, the monoglycerides and fatty acids are resynthesized into new molecules of triglycerides that enter the lymph as minute, dispersed droplets called “chylomicrons”. The VLDLs transport triglycerides synthesized in the liver mainly to the adipose tissue.
Thermal body receptors
Deep body thermal receptors are found predominantly in the spinal cord, in the great veins in the upper abdomen and thoracic cavity and the abdominal viscera. They are sensitive to the body’s core temperature. They detect mainly cold rather than warmth and are concerned with preventing low body temperature.
Cell membrane permeability factors
Cell membrane permeability is directly proportional to the concentration gradient across the cell membrane as shown by the formula: Net diffusion is proportional to (Co−Ci) where Co is the concentration outside the cell membrane and Ci is the concentration inside the cell membrane. Decreased thickness of the membrane provides a smaller distance for the molecules to travel and hence increases cell membrane permeability. As the cell membrane is a lipid bilayer, it is more permeable to lipophilic molecules. Large membrane surface area and increased temperature also increase cell membrane permeability.
Fat metabolism
Fats cannot be converted to glucose because the pyruvate dehydrogenase reaction is irreversible and there are no alternative pathways that will generate pyruvate from acetyl-CoA. Acetyl-CoA is already an activated molecule and it cannot be activated further to overcome the free energy difference involved in pyruvate formation.
RNA polymerase
RNA polymerase is an enzyme involved in the assembly of the RNA molecule. It attaches to the promoter sequence of the DNA strand and initiates RNA formation. Then, it causes unwinding of two turns of DNA helix and separates the two strands. It forms a hydrogen bond between the end base of the DNA strand and the RNA nucleotide base. It recognizes the chain-terminating sequence in DNA and breaks away from the DNA strand. Once finished on a particular strand of DNA, it can be used on further DNA molecules.
Resting membrane potential
Resting membrane potential (RMP) is the voltage (charge) difference across the cell membrane when the cell is at rest. RMP occurs when extracellular fluid (ECF) is positively charged and intracellular fluid (ICF) is negatively charged, with a difference of around 90 mV. The ion flow through the cell membrane is essential to maintain the RMP. Na+ and Cl- will flow through the membrane from the ECF to ICF. In contrast, K+ will flow from the ICF to the ECF. In the resting state, the cell membrane is more permeable to K+ and Cl- than to Na+. Because of the high outflow of K+ and inflow of Cl-, the transmembrane potential will remain negative.
ATP
Adenine triphosphate (ATP) is the most important energy source for cells; it releases energy by breaking its high-energy phosphate bonds, producing adenine diphosphate and then monophosphate. Phosphocreatine can donate its phosphate to form new ATP. Acetyl-CoA is another high-energy compound, important in the citric acid cycle. Anaerobic metabolism of glycogen has a net production of 3 mol of ATP, whereas the net gain from metabolising glucose is only 2 mol of ATP. The reason for this difference is that 1 mol of ATP is used to phosphorylate glucose when it enters the cell from the blood. Glycogen is already present in the cell.
ATP synthase, also known as “mitochondrial complex V”, is located in the inner surface of the mitochondrial inner membrane (F0 domain) and the mitochondrial matrix (F1 domain). ATP synthase is responsible for the synthesis of ATP from ADP using the energy provided by the electron transport chain, and its activity increases in cells when the ATP/ADP ratio is low. Cardiac and skeletal contractility are strongly dependent on the mitochondria.
Golgi apparatus
The Golgi apparatus is an organelle found in almost all eukaryotic cells. Conspicuously, erythrocytes do not have a golgi apparatus. It has two sides (cis and trans) and the membranes at one end of the stack differ in both composition and in thickness from those at the opposite end. The Golgi apparatus receives protein synthesized by the RER (rough endoplasmic reticulum), processes it in many post-translational modifications (i.e. glycosylation and phosphorylation), and packages it in secretory vesicles.
Citric acid cycle
The citric acid cycle takes place inside the mitochondria. The cycle uses 1 molecule of acetyl-CoA as a significant carbon input in each cycle. Per 1 molecule of glucose, 2 molecules of acetyl-CoA are produced in glycolysis, generating 2 ATP, 6 NADH, 2 FADH2, 4 CO2, and 6 H+ in the citric acid cycle. NADH and FADH2 molecules are used in the electron transport chain, resulting in the net synthesis of 12 ATP per acetyl-CoA. The cycle can be entered through intermediates other than acetyl-CoA, for example, citrate and succinate.
The tricarboxylic acid (TCA) cycle is an aerobic metabolic pathway that takes place in the mitochondria. It oxidizes acetyl-CoA to CO2 and generates high amounts of redox cofactors (NADH/FADH2) that are utilized for ATP synthesis in the electron transport chain. Intermediates in the TCA cycle include citrate, alpha ketoglutarate, succinyl-CoA, malate, and oxaloacetate. Oxaloacetate is the primary precursor for gluconeogenesis in the fasting state. Glucose is converted into pyruvate through glycolysis.
During aerobic respiration, glucose is catabolized in 3 metabolic pathways: glycolysis, the tricarboxylic acid cycle (TCA or Krebs cycle), and oxidative phosphorylation. Most ATP is formed in the inner mitochondrial membrane by oxidative phosphorylation (34 ATP). Glycolysis occurs in the cytosol of cells and results in a net gain of 2 ATP per 1 molecule of glucose. The Krebs cycle occurs in the mitochondrial matrix and produces 3 NADH, 1 FADH2, 1 GTP, and 2 ATP.
The citric acid cycle is the major metabolic hub of the cell. Its intermediates are used in the biosynthesis of various compounds. Oxaloacetate is used for the synthesis of amino acids. These non-carbohydrate substrates can be further used in gluconeogenesis. Citrate is utilized in the synthesis of fatty acids and sterols. Succinyl-CoA provides carbon atoms for porphyrins.
Cyclic AMP
Cyclic AMP is a second messenger molecule formed from ATP by the enzyme adenylyl cyclase. It is inactivated by another enzyme, phosphodiesterase. Phosphodiesterase may be inhibited by caffeine and theophylline. Cyclic AMP works by activating protein kinase A.
Vasopressin stimulates adenylate cyclase via the activation of the vasopressin 2 receptor (V2R), more officially called “arginine vasopressin receptor 2” (“AVPR2”). AVPR2 belongs to the subfamily of G-protein–coupled receptors. Its activity is mediated by the Gs type of G-proteins, which stimulate adenylate cyclase. AVPR2 is expressed in the kidney tubule, predominantly in the membrane of cells of the distal convoluted tubule and collecting ducts, in fetal lung tissue and lung cancer, the last two being associated with alternative splicing. AVPR2 is also expressed outside the kidney in vascular endothelium.
Glucagon stimulates adenylate cyclase via the activation of the glucagon receptor. The glucagon receptor is a 62 kDa protein that is activated by glucagon and is a member of the class B G-protein–coupled family of receptors, coupled to G alpha i, Gs, and (to a lesser extent) G alpha q. Glucagon receptors are mainly expressed in the liver and kidneys, with lesser amounts found in the heart, adipose tissue, spleen, thymus, adrenal glands, pancreas, cerebral cortex, and gastrointestinal tract.
Calcitonin stimulates adenylate cyclase. The calcitonin receptor, localized to osteoclasts, the kidney, and regions of the brain, is a G-protein–coupled receptor. It is coupled by Gs to adenylate cyclase, and thereby to the generation of cAMP in target cells.
Estrogen does not stimulate adenylate cyclase.
Fast twitch and slow twitch muscle fibres
Fast-twitch muscle fibers have a lower number of mitochondria as compared to slow muscle fibers. Therefore, their oxidative capacity is low. They also differ from slow fibers in that they have more extensive sarcoplasmic reticulum, larger fibers, larger amounts of glycolytic enzymes, and a less extensive blood supply in the form of low capillary density.
Biological oxidation
Biological oxidation is a process in which cells use an electron transport chain to transfer electrons from substrates to oxygen. Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for energy production. The end products of the flavoprotein–cytochrome system are carbon dioxide and water, which are exhaled in each breath. In oxidative phosphorylation, NADH is oxidized to NAD+.
Potassium
Potassium is mainly an intracellular cation. Increasing the extracellular potassium concentration would result in depolarization of the membrane potentials. This is the result of an increase in the equilibrium potential of potassium. The depolarization activates voltage-gated sodium channels but also decreases sodium influx. This depolarization does not generate an action potential; rather, it leads to a phenomenon called “accommodation”. Due to the decrease in a gradient across the cell membrane, the hyperpolarizing outward permeability of potassium ions will decrease, and inward potassium current will increase. The activity of the sodium-potassium ATPase pump is also increased.
DNA bases
Adenine and guanine are purines. Cytosine, thymine and uracil are pyrimidines. In DNA, adenine binds to thymine, and guanine to cytosine. In RNA, adenine binds to uracil.
Each DNA strand is composed of simple monomeric units called “nucleotides”. Each nucleotide consists of the sugar deoxyribose, a phosphate group, and a nitrogen-containing nucleobase. Each phosphate group is attached to the sugar of the next nucleotide by covalent bonds. The base of one DNA strand pairs with its opposite by weak cross-linkages. Adenine binds to thymine, and cytosine binds to guanine. It takes three bases to code for a single amino acid.