This document discusses minerals and their metabolism. It begins by classifying minerals as macrominerals or microminerals and describes their functions. Important macrominerals like sodium and potassium are then discussed in detail. Sodium is described as the major electrolyte found extracellularly and its absorption via the sodium-potassium pump is explained. The document outlines the pump's mechanism and regulation. Potassium is summarized as the main intracellular cation, with its distribution and role in muscle and nerve function. Clinical implications of abnormalities in sodium and potassium levels are also briefly mentioned.

1. Biochem 612
Minerals and Their Metabolism

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-
1. Calcification of bones
2. Blood coagulation
3. Neuromuscular irritability
4. Acid-base equilibrium
5. Fluid balance
6. 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.
• Lowers 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.
• The 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. • The 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.