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Biochemistry - NEETMDS- courses
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Biochemistry

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.

The Hemoglobin Buffer Systems

These buffer systems are involved in buffering CO2 inside erythrocytes. The buffering capacity of hemoglobin depends on its oxygenation and deoxygenation. Inside the erythrocytes, CO2 combines with H2O to form carbonic acid (H2CO3) under the action of carbonic anhydrase.

At the blood pH 7.4, H2CO3 dissociates into H+ and HCO3 and needs immediate buffering.

BIOLOGICAL ROLES OF LIPID

Lipids have the common property of being relatively insoluble in water and soluble in nonpolar solvents such as ether and chloroform. They are important dietary constituents not only because of their high energy value but also because of the fat-soluble vitamins and the essential fatty acids contained in the fat of natural foods

Nonpolar lipids act as electrical insulators, allowing rapid propagation of depolarization waves along myelinated nerves

Combinations of lipid and protein (lipoproteins) are important cellular constituents, occurring both in the cell membrane and in the mitochondria, and serving also as the means of transporting lipids in the blood.

The input to fatty acid synthesis is acetyl-CoA, which is carboxylated to malonyl-CoA.

The ATP-dependent carboxylation provides energy input. The CO2 is lost later during condensation with the growing fatty acid. The spontaneous decarboxylation drives the condensation. 

 fatty acid synthesis
acetyl-CoA + 7 malonyl-CoA + 14 NADPH palmitate + 7 CO2 + 14 NADP+ + 8 CoA

ATP-dependent synthesis of malonate:
8 acetyl-CoA + 14 NADPH + 7 ATP palmitate + 14 NADP+ + 8 CoA + 7 ADP + 7 Pi

Fatty acid synthesis occurs in the cytosol. Acetyl-CoA generated in the mitochondria is transported to the cytosol via a shuttle mechanism involving citrate

Glycolysis Pathway

 

The reactions of Glycolysis take place in the cytosol of cells.

Glucose enters the Glycolysis pathway by conversion to glucose-6-phosphate. Initially, there is energy input corresponding to cleavage of two ~P bonds of ATP. 

1. Hexokinase catalyzes:  glucose + ATP → glucose-6-phosphate + ADP

ATP binds to the enzyme as a complex with Mg++.

The reaction catalyzed by Hexokinase is highly spontaneous 

 

2. Phosphoglucose Isomerase catalyzes: 

glucose-6-phosphate (aldose) → fructose-6-phosphate (ketose)

The Phosphoglucose Isomerase mechanism involves acid/base catalysis, with ring opening, isomerization via an enediolate intermediate, and then ring closure .

3. Phosphofructokinase catalyzes: 

fructose-6-phosphate + ATP  → fructose-1,6-bisphosphate + ADP

The Phosphofructokinase reaction is the rate-limiting step of Glycolysis. The enzyme is highly regulated. 

 

4. Aldolase catalyzes: 

fructose-1,6-bisphosphate   → dihydroxyacetone phosphate + glyceraldehyde-3-phosphate

The Aldolase reaction is an aldol cleavage, the reverse of an aldol condensation.

5. Triose Phosphate Isomerase (TIM) catalyzes

dihydroxyacetone phosphate (ketose) glyceraldehyde-3-phosphate (aldose)

Glycolysis continues from glyceraldehydes-3-phosphate

The equilibrium constant (Keq) for the TIM reaction favors dihydroxyacetone phosphate, but removal of glyceraldehyde-3-phosphate by a subsequent spontaneous reaction allows throughput. 

 

6. Glyceraldehyde-3-phosphate Dehydrogenase catalyzes:

glyceraldehyde-3-phosphate + NAD+ + Pi  → 1,3,bisphosphoglycerate + NADH + H+

This is the only step in Glycolysis in which NAD+ is reduced to NADH

A cysteine thiol at the active site of Glyceraldehyde-3-phosphate Dehydrogenase has a role in catalysis . 

7. Phosphoglycerate Kinase catalyzes:

1,3-bisphosphoglycerate + ADP  →  3-phosphoglycerate + ATP

This transfer of phosphate to ADP, from the carboxyl group on 1,3-bisphosphoglycerate, is reversible

8. Phosphoglycerate Mutase catalyzes:  3-phosphoglycerate → 2-phosphoglycerate

Phosphate is shifted from the hydroxyl on C3 of 3-phosphoglycerate to the hydroxyl on C2.  

9. Enolase catalyzes:  2-phosphoglycerate  → phosphoenolpyruvate + H2O

 

This Mg++-dependent dehydration reaction is inhibited by fluoride. Fluorophosphate forms a complex with Mg++ at the active site .

10. Pyruvate Kinase catalyzes:  phosphoenolpyruvate + ADP  → pyruvate + ATP

This transfer of phosphate from PEP to ADP is spontaneous

Balance sheet for high energy bonds of ATP: 

  • 2 ATP expended
  • 4 ATP produced (2 from each of two 3C fragments from glucose) 
  • Net Production of 2~ P bonds of ATP per glucose

Growth hormone

Growth hormone (GH or HGH), also known as somatotropin or somatropin, is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans.

Growth hormone is a single-chain polypeptide that is synthesized, stored, and secreted by somatotropic cells within the lateral wings of the anterior pituitary gland.

Regulation of growth hormone secretion

Secretion of growth hormone (GH) in the pituitary is regulated by the neurosecretory nuclei of the hypothalamus. These cells release the peptides Growth hormone-releasing hormone (GHRH or somatocrinin) and Growth hormone-inhibiting hormone (GHIH or somatostatin) into the hypophyseal portal venous blood surrounding the pituitary.

GH release in the pituitary is primarily determined by the balance of these two peptides, which in turn is affected by many physiological stimulators (e.g., exercise, nutrition, sleep) and inhibitors (e.g., free fatty acids) of GH secretion.

Regulation

Stimulators of growth hormone (GH) secretion include peptide hormones, ghrelin, sex hormones, hypoglycemia, deep sleep, niacin, fasting, and vigorous exercise.

Inhibitors of GH secretion include somatostatin, circulating concentrations of GH and IGF-1 (negative feedback on the pituitary and hypothalamus), hyperglycemia, glucocorticoids, and dihydrotestosterone.

Clinical significance

The most common disease of GH excess is a pituitary tumor composed of somatotroph cells of the anterior pituitary. These somatotroph adenomas are benign and grow slowly, gradually producing more and more GH excess. The adenoma may become large enough to cause headaches, impair vision by pressure on the optic nerves, or cause deficiency of other pituitary hormones by displacement.

ZINC

The enzyme RNA polymerase, which is required for transcription, contains zinc and it is essential for protein bio synthesis.

Deficiency in Zinc leads to poor wound healing, lesions of skin impaired spermatogenesis, hyperkeratosis, dermatitis and alopecia

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