Glucagon

Glucagon, a peptide hormone synthesized and secreted from the α-cells of the islets of Langerhans of pancreas, raises blood glucose levels. The pancreas releases glucagon when blood sugar (glucose) levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is released into the bloodstream. Glucagon and insulin are part of a feedback system that keeps blood glucose levels at a stable level.

Regulation and function

Secretion of glucagon is stimulated by hypoglycemia, epinephrine, arginine, alanine, acetylcholine, and cholecystokinin.

Secretion of glucagon is inhibited by somatostatin, insulin, increased free fatty acids and keto acids into the blood, and increased urea production.

The amino acids buffer system

Amino acids contain in their molecule both an acidic (− COOH) and a basic (− NH₂) group. They can be visualized as existing in the form of a neutral zwitterion in which a hydrogen atom can pass between the carboxyl and amino groups. 

By the addition or subtraction of a hydrogen ion to or from the zwitterion, either the cation or anion form will be produced 

Thus, when OH⁻ ions are added to the solution of amino acid, they take up H⁺ from it to form water, and the anion is produced. If H⁺ ions are added, they are taken up by the zwitterion to produce the cation form. In practice, if NaOH is added, the salt H₂N - CH₂ - COONa would be formed. and the addition of HCl would result in the formation of amino acid hydrochloride.

COPPER

The normal serum level of copper is 25 to 50 mg/dl.

Functions of copper

(a) Copper is necessary for iron absorption and incorporation of iron into hemoglobin.

(b) It is very essential for tyrosinase activity

(c) It is the co-factor for vitamin C requiring hydroxylation

(d) Copper increases the level of high density lipo protein and protects the heart.

Wilson’s disease

In case of Wilson’s disease ceruloplasmin level in blood is drastically reduced.

Wilson’s disease leads to

(i) Accumulation of copper in liver leads to hepatocellular degeneration and cirrhosis

(ii) Deposition of copper in brain basal ganglia leads to leticular degeneration

(iii) Copper deposits as green pigmented ring around cornea and the condition is called as Kayser-Kleischer ring

Over accumulation of copper can be treated by consumption of diet containg low copper and injection of D-penicillamine, which excretes copper through urine.

Menke’s kidney hair syndrome

 It is X-linked defect. In this condition copper is absorbed by GI tract, but cannot be transported to blood. The defect in transport of copper to blood is due to absence of an intracellular copper binding ATPase.

FACTORS AFFECTING ENZYME ACTIVITY

Velocity or rate of enzymatic reaction is assessed by the rate of change in concentration of substrate or product at a given time duration. Various factors which affect the activity of enzymes include:

1. Substrate concentration

2. Enzyme concentration

3. Product concentration

4. Temperature 5. Hydrogen ion concentration (pH)

6. Presence of activators

7. Presence of inhibitor

Effect of substrate Concentration :  Reaction velocity of an enzymatic process increases with constant enzyme concentration and increase in substrate concentration.

Effect of enzyme Concentration: As there is optimal substrate concentration, rate of an enzymatic reaction or velocity (V) is directly proportional to the enzyme concentration.

Effect of product concentration In case of a reversible reaction catalyzed by a enzyme, as per the law of mass action the rate of reaction is slowed down with equilibrium. So, rate of reaction is slowed, stopped or even reversed with increase in product concentration

Effect of temperature: Velocity of enzymatic reaction increases with temperature of the medium which they are most efficient and the same is termed as optimum temperature.

Effect of pH: Many enzymes are most efficient in the region of pH 6-7, which is the pH of the cell. Outside this range, enzyme activity drops off very rapidly. Reduction in efficiency caused by changes in the pH is due to changes in the degree of ionization of the substrate and enzyme.

Highly acidic or alkaline conditions bring about a denaturation and subsequent loss of enzymatic activity

Exceptions such as pepsin (with optimum pH 1-2), alkaline phosphatase (with optimum pH 9-10) and acid phosphatase (with optimum pH 4-5)

Presence of activators Presence of certain inorganic ions increases the activity of enzymes. The best examples are chloride ions activated salivary amylase and calcium activated lipases.

Effect of Inhibitors The catalytic enzymatic reaction may be inhibited by substances which prevent the formation of a normal enzyme-substrate complex. The level of inhibition then depends entirely upon the relative concentrations of the true substrate and the inhibitor

COENZYMES

 Enzymes may be simple proteins, or complex enzymes.

A complex enzyme contains a non-protein part, called as prosthetic group (co-enzymes).

Coenzymes are heat stable low molecular weight organic compound. The combined form of protein and the co-enzyme are called as holo-enzyme. The heat labile or unstable part of the holo-enzyme is called as apo-enzyme. The apo-enzyme gives necessary three dimensional structures required for the enzymatic chemical reaction.

Co-enzymes are very essential for the biological activities of the enzyme.

Co-enzymes combine loosely with apo-enzyme and are released easily by dialysis. Most of the co-enzymes are derivatives of vitamin B complex

Buffers           

• Biological systems use buffers to maintain pH.

• Definition: A buffer is a solution that resists a significant change in pH upon addition of an acid or a base.

• Chemically: A buffer is a mixture of a weak acid and its conjugate base

• Example: Bicarbonate buffer is a mixture of carbonic acid (the weak acid) and the bicarbonate ion (the conjugate base): H₂CO₃ + HCO₃ ^–

• All OH- or H+ ions added to a buffer are consumed and the overall [H+ ] or pH is not altered

H₂CO₃ + HCO₃ ^- + H⁺ <- -> 2H₂CO₃

H₂CO₃ + HCO₃ -  +  OH^-  <- -> 2HCO₃  ^- + H₂O

• For any weak acid / conjugate base pair, the buffering range is its pKa +1.

It should be noted that around the pK_a the pH of a solution does not change appreciably even when large amounts of acid or base are added. This phenomenon is known as buffering. In most biochemical studies it is important to perform experiments, that will consume H⁺ or OH^- equivalents, in a solution of a buffering agent that has a pK_a near the pH optimum for the experiment.

Most biologic fluids are buffered near neutrality. A buffer resist a pH change and consists of a conjugate acid/base pair.

Important Physiological Buffers include carbonate (H₂CO₃/HCO₃^-),

Phosphate (H₂PO^-₄ /HPO^2-₄) and various protiens