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Biochemistry

BIOLOGICAL BUFFER SYSTEMS 

Cells and organisms maintain a specific and constant cytosolic pH, keeping biomolecules in their optimal ionic state, usually near pH 7. In multicelled organisms, the pH of the extracellular fluids (blood, for example) is also tightly regulated. Constancy of pH is achieved primarily by biological buffers : mixtures of weak acids and their conjugate bases 

Body fluids and their principal buffers


Body fluids                     Principal buffers

Extracellular fluids        {Biocarbonate buffer Protein buffer } 

Intracellular fluids         {Phosphate buffer, Protein }

Erythrocytes                 {Hemoglobin buffer}

PHOSPHORUS

Serum level of phosphate is 3-4 mg/dl for adults and 5-6 mg/dl in children. Consumption of calcitriol increases phosphate absorption.

Functions of phosphorus
(a) Plays key role in formation of tooth and bone

(b) Production of high energy phosphate compounds such as ATP, CTP, GTP etc.,

(c) Synthesis of nucleotide co-enzymes such as NAD and NADP

(d) Formation of phosphodiester backbone structure for DNA and RNA synthesis

Hypophosphatemia is the condition which leads to decrease in absorption of phosphorus. it leads to hypercalcamia

Hyperphosphatemia, increase in absorption of phosphate was noticed. Hyperphosphatemia leads to cell lysis, hypocalcemia and thyrotoxicosis.

Vitamin B6: Pyridoxine, Pyridoxal, Pyridoxamine

Aids  in protein metabolism and red blood cell formation. It is also involved in the body’s production of chemicals such as insulin and hemoglobin.

Vitamin B6 Deficiency Deficiency symptoms include skin disorders, dermatitis, cracks at corners of mouth, anemia, kidney stones, and nausea. A vitamin B6 deficiency in infants can cause mental confusion.

FATTY  ACIDS

Fatty acids consist of a hydrocarbon chain with a carboxylic acid at one end.

• are usually in esterified form as major components of other lipids

• are often complexed in triacylglycerols (TAGs)

• most have an even number of carbon atoms (usually 14 to 24)

• are synthesized by concatenation of C2 units.

• C16 & C18 FAs are the most common FAs in higher plants and animals

• Are either:

—saturated (all C-C bonds are single bonds) or

—unsaturated (with one or more double bonds in the chain)

—monounsaturated (a single double bond)

1.Example of monounsaturated FA: Oleic acid 18:1(9) (the number in unsaturated FA parentheses indicates that the double bond is between carbons 9 & 10)

2. Double bonds are almost all in the cis conformation

 

—polyunsaturated (more then one double bond)

Polyunsaturated fatty acids contain 2 or more double bonds. They usually occur at every third carbon atom towards the methyl terminus (-CH3 ) of the molecule. Example of polyunsaturated FA: Linoleic acid 18:2(9,12)

• the number of double bonds in FAs varies from 1 to 4 (usually), but in most bacteria it is rarely more than 1

Saturated FAs are highly flexible molecules that can assume a wide range of conformations because there is relatively free rotation about their C-C bonds.

Functions of  lipids

1. They are the concentrated fuel reserve of the body  (triacylglycerols).

2. Lipids are the constituents of membrane structure and regulate the membrane permeability (phospholipids  and cholesterol).

3. They serve as a source of fat soluble vitamins (A, D, E and K).

4. Lipids are important as cellular metabolic regulators (steroid  hormones and prostaglandins).

5. Lipids protect the internal organs, serve as insulating materials and give shape and smooth appearance to the body.

Insulin

Insulin is a polypeptide hormone synthesized in the pancreas by β-cells, which construct a single chain molecule called proinsulin. 

Insulin, secreted by the β-cells of the pancreas in response to rising blood glucose levels, is a signal that glucose is abundant.

Insulin binds to a specific receptor on the cell surface and exerts its metabolic effect by a signaling pathway that involves a receptor tyrosine kinase phosphorylation cascade.

The pancreas secretes insulin or glucagon in response to changes in blood glucose.

Each cell type of the islets produces a single hormone: α-cells produce glucagon; β-cells, insulin; and δ-cells, somatostatin.

Insulin secretion

When blood glucose rises, GLUT2 transporters carry glucose into the b-cells, where it is immediately converted to glucose 6-phosphate by hexokinase IV (glucokinase) and enters glycolysis. The increased rate of glucose catabolism raises [ATP], causing the closing of ATP-gated K+ channels in the plasma membrane. Reduced efflux of K+ depolarizes the membrane, thereby opening voltage-sensitive Ca2+ channels in the plasma membrane. The resulting influx of Ca2+ triggers the release of insulin by exocytosis.

Insulin lowers blood glucose by stimulating glucose uptake by the tissues; the reduced blood glucose is detected by the β-cell as a diminished flux through the hexokinase reaction; this slows or stops the release of insulin. This feedback regulation holds blood glucose concentration nearly constant despite large fluctuations in dietary intake.

 

Insulin counters high blood glucose

Insulin stimulates glucose uptake by muscle and adipose tissue, where the glucose is converted to glucose 6-phosphate. In the liver, insulin also activates glycogen synthase and inactivates glycogen phosphorylase, so that much of the glucose 6-phosphate is channelled into glycogen.

Diabetes mellitus, caused by a deficiency in the secretion or action of insulin, is a relatively common disease. There are two major clinical classes of diabetes mellitus: type I diabetes, or insulin-dependent diabetes mellitus (IDDM), and type II diabetes, or non-insulin-dependent diabetes mellitus (NIDDM), also called insulin-resistant diabetes. In type I diabetes, the disease begins early in life and quickly becomes severe. IDDM requires insulin therapy and careful, lifelong control of the balance between dietary intake and insulin dose.

Characteristic symptoms of type I (and type II) diabetes are excessive thirst and frequent urination (polyuria), leading to the intake of large volumes of water (polydipsia)

Type II diabetes is slow to develop (typically in older, obese individuals), and the symptoms are milder.

PROPERTIES OF TRIACYLGTYCEROLS

1. Hydrolysis : Triacylglycerols undergo stepwise enzymatic hydrolysis to finally liberate free fatty acids and glycerol.

The process of hydrolysis, catalysed by lipases is important for digestion of fat in the gastrointestinal tract and fat mobilization from the adipose tissues.

2. Saponification : The hydrolysis of triacylglycerols by alkali to produce glycerol and soaps is known as saponification.

3.Rancidity: Rancidity is the term used to represent the deterioration of fats and oils resulting in an unpleasant taste. Fats containing unsaturated fatty acids are more susceptible to rancidity.

Hydrolytic rancidity occurs due to partial hydrolysis of triacylglycerols by bacterial enzymes.

Oxidative rancidity is due to oxidation of unsaturated fatty acids.

This results in the formation of unpleasant products such as dicarboxylic acids, aldehydes, ketones etc.

 

Antioxidants : The substances which can prevent the occurrence of oxidative rancidity are known as antioxidants.

Trace amounts of antioxidants such as tocopherols  (vitamin E), hydroquinone, gallic acid and c,-naphthol are added to the commercial preparations of fats and oils to prevent rancidity. Propylgallate, butylatedhydroxyanisole (BHA)  and butylated hydroxytoluene (BHT) are the antioxidants used in food preservation.

Lipid peroxidation in vivo: In the living cells, lipids undergo oxidation to produce peroxides and free radicals which can damage the tissue. .

The free radicals are believed to cause inflammatory diseases, ageing, cancer , atherosclerosis etc

Iodine number : lt is defined as the grams (number)  of iodine absorbed by 100 g of fat or oil. lodine number is useful to know the relative

unsaturation of fats, and is directly proportional to the content of unsaturated fatty acids

Determination of iodine number will help to know the degree of adulteration of a given oil

Saponification number : lt is defined as the mg  (number) of KOH required to hydrolyse (saponify) one gram of fat or oiL

Reichert-Meissl (RM)  number: lt is defined as the number of ml 0.1 N KOH required to completely neutralize the soluble volatile fatty acids distilled from 5 g fat. RM number is useful in testing the purity of butter since it contains a good concentration of volatile fatty acids (butyric acid, caproic acid and caprylic acid).

Acid number : lt is defined as the number of mg of KOH required to completely neutralize free fatty acids present in one gram fat or oil. In normal circumstances, refined oils should be free from any free fatty acids.

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