LECTURE 1 intro,sodium,potassium.pptx

Biochemistry

1. Biochem 612 Minerals and Their M etabolism

2. Major Concepts A . Study and classify elements present in the body. B. Study in detail the minerals or principal elements. C. Study in detail the trace elements.

3. Introduction Minerals are inorganic compounds that are required for the body as one of the nutrients. The inorganic elements (minerals) constitute only small proportion of the body weight. Human body needs a number of minerals for its functioning. FUNCTIONS Minerals perform many vital functions which are essential for existence of organism- Calcification of bones Blood coagulation Neuromuscular irritability Acid-base equilibrium Fluid balance Osmotic regulation

4. CLASSIFICATION OF MINERALS 1. Macrominerals Required in excess of 100mg/day Na, K, Ca ++, Cl, P, S, Mg. 2. Microminerals Required in amounts less than 100mg/day Fe , Cu, Zn, Mo, I, Fl , Cr, CO, Mn

5. SODIUM Sodium is the chief electrolyte which is found in large conc. in extracellular fluid compartment . Approx . body distribution of sodium is The sodium is found in the body mainly in associated form as NaCl and NaHCO3. Compartments Concentration ( mmol /L) Intracellular 10 Extracellular 140 Plasma 140

6. Sources: Sodium is widely distributed in food material more in animal sources than plants. Major source is table-salt used in cooking. It is also found in cheese, butter. Daily Requirement: • 1-3.5 g of Na is required daily for adults. • Infants need 0.1-0.5 g • Children 0.3-2.5 g daily

7. Absorption of Sodium Sodium is absorbed by sodium pump situated in basal and lateral plasma membrane of intestinal and renal cells. Na-pump actively transports Na into extracellular fluid.

8. SODIUM PUMP Na-pump is an enzyme, Na+-K+-ATPase. It is a glycoprotein composed of 2 α and 2 β chains. Its activity depends on presence of Na+ and K+ and requires ATP and Mg++ ions as cofactor. The enzyme hydrolyses a high energy phosphate bond of ATP . It uses the energy to transport three Na+ ions outside and simultaneously two K+ ions inside across the cell membrane . The Na-pump is very active in those cells where activities depend largely on transmembrane Na+ fluxes, e.g. nervous , muscle fibers, renal tubules cells, intestinal mucosal cells. CLASS ACTIVITY: What is the chemical nature of sodium pump?

9. Forms of Sodium Pump and Mechanism Na +-K+ ATPase exists in two forms: E1 and E2. The E1 form: E1 has an inward –facing high affinity Na+ binding site and reacts with ATP to form the activated product E1~P only when Na+ is bound.  Presents its ion binding and phosphate binding sites on the cytoplasmic surface of the membrane . Three sodium ions from cytoplasm bind with the ion binding sites of E1. This leads to the phosphorylation of aspartate residue of E1 with the help of ATP and Mg++. This results in conformational change and E1 becomes E2.

10. E2 form has an outward –facing high affinity K+ binding site E 2 exposes both ion binding and phosphate binding sites on the extracellular surface of the membrane. L owers the affinity of the ATPase for Na+ and releases it into the ECF. On the contrary, now the K + ions from ECF bind to the respective ion binding site of the pump. This lowers the affinity of E2 for phosphate . This dephosphorylation changes the conformation of E2 to E1 again and lowers its affinity for K+ ions. This leads to release of the K+ ions from ATPase into the cell . CLASS ACTIVITY: Why Na+-K+ pump is known as P-Type ion transporter?

11. MECHANISM

12. Regulation of Sodium Pump The Na/K+-ATPase is upregulated by cAMP . Substances causing an increase in cAMP upregulate the Na+/K+-ATPase. These include the ligands of the Gs -coupled GPCRs. T he regulation of Na(+)-K(+)-ATPase in various tissues is under the control of a number of circulating hormones like aldosterone , thyroid hormone, catecholamines. Catecholamines provides short term regulation while aldosterone, thyroid hormone provides long term regulation.

13. Inhibitors • Ouabain : A glycoside of a steroid and digitalis is the cardiotonic drug which inhibits the Na+-K+ pump by blocking the step of dephosphorylation .

14. CLASS ACTIVITES Na+-K+ pump is a tetramer. On which subunits are the binding sites for Na+ and K+? What is the effect of steroids on Na+-K+ pump ? How is Na+-K+ pump regulated? When Na+-K+ pump is dephosphorylated? How E2 form of Na+-K+ pump is converted to E1 form?

15. T he sodium transported actively by Na pump diffuses into the cell Active absorption of Na+ is coupled with glucose absorption or amino acid absorption . Excretion of Na: Every 24 hours approximately, 25000 mmol of sodium are filtered by the kidneys. However, due to tubular reabsorption less than 1 per cent of this sodium appears in the urine (100-200 mM /day ). Approximately 70 per cent of the filtered sodium is reabsorbed in proximal tubule. Further 20–30 per cent of filtered Na+ is reabsorbed by ascending loop of Henle.

16. Functions Fluid balance Neuromuscular excitability Maintenance of viscosity of blood

17. CLINICAL ASPECT Clinical conditions related to sodium are of two major types: I. Hypernatraemia II. Hyponatraemia . Hypernatraemia Deficit of water relative to sodium Causes Specific conditions in which hypernatraemia occurs are Simple dehydration Diabetes insipidus Osmotic loading Excess sodium intake Steroid therapy Hyponatraemia Causes Excessive sweating Kidney diseases Congestive heart failure Gastrointestinal loss

18. POTASSIUM Potassium is the major intracellular cation. It is widely distributed in the body fluids and tissues as follows:

19. Source It is widely distributed in the vegetable foods. An average amount of 4 g of potassium is present in the diet. Potassium is easily absorbed. Metabolism As soon as it is absorbed, potassium enters the cells. It is excreted in the urine. The conc. of intracellular K + is 150 mEq /L which is roughly equal to the conc. Of sodium outside the cell. The normal conc. of plasma potassium is 3.5-5 mEq /L. The Na+-K+ ATPase or sodium pump maintains this concentration gradient. Potassium is continuously filtered by the glomeruli of the kidney and reabsorbed by the cells of proximal convoluted tubules. Potassium ions are also secreted in distal tubule in exchange for sodium

20. FUNCTIONS It influences the muscular activity. Involved in acid-base balance. It has an important role in cardiac function. Certain enzymes such as pyruvate kinase require K+ as cofactor. Involved in neuromuscular irritability and nerve conduction process.

21. CLINICAL ASPECT Hyperkalaemia Causes Kidney failure Tissue damage: Addison’s disease Diabetes mellitus Hypokalaemia Low serum K+ usually results from the depletion of total body K + Causes Dietary deficiency Loss of K+ in GI secretions Loss of K+ in urine Loss of extracellular potassium into the intracellular space inherited disorder called familial periodic paralysis

22. Suggested Readings MN Chatterjea and R.Shinde .   Text book of Medical biochemistry. Eighth Edition, 2013.