NEET MDS Lessons
Biochemistry
Thyroid Hormones
Thyroid hormones (T4 and T3) are tyrosine-based hormones produced by the follicular cells of the thyroid gland and are regulated by TSH made by the thyrotropes of the anterior pituitary gland, are primarily responsible for regulation of metabolism. Iodine is necessary for the production of T3 (triiodothyronine) and T4 (thyroxine).
A deficiency of iodine leads to decreased production of T3 and T4, enlarges the thyroid tissue and will cause the disease known as goitre.
Thyroid hormones are transported by Thyroid-Binding Globulin
Thyroxine binding globulin (TBG), a glycoprotein binds T4 and T3 and has the capacity to bind 20 μg/dL of plasma.
Diseases
1. Hyperthyroidism (an example is Graves Disease) is the clinical syndrome caused by an excess of circulating free thyroxine, free triiodothyronine, or both. It is a common disorder that affects approximately 2% of women and 0.2% of men.
2 Hypothyroidism (an example is Hashimoto’s thyroiditis) is the case where there is a deficiency of thyroxine, triiodiothyronine, or both.
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
Riboflavin: Vitamin B2
Riboflavin, or vitamin B2, helps to release energy from foods, promotes good vision, and healthy skin. It also helps to convert the amino acid tryptophan (which makes up protein) into niacin.
RDA Males: 1.3 mg/day; Females: 1.1 mg/day
Deficiency : Symptoms of deficiency include cracks at the corners of the mouth, dermatitis on nose and lips, light sensitivity, cataracts, and a sore, red tongue.
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.
Thiamin: Vitamin B1
Thiamin, or vitamin B1, helps to release energy from foods, promotes normal appetite, and is important in maintaining proper nervous system function.
RDA (Required Daily allowance) Males: 1.2 mg/day; Females: 1.1 mg/day
Thiamin Deficiency
Symptoms of thiamin deficiency include: mental confusion, muscle weakness, wasting, water retention (edema), impaired growth, and the disease known as beriberi.
IRON
The normal limit for iron consumption is 20 mg/day for adults, 20-30 mg/day for children and 40 mg/day for pregnant women.
Milk is considered as a poor source of iron.
Factors influencing absorption of iron Iron is absorbed by upper part of duodenum and is affected by various factors
(a) Only reduced form of iron (ferrous) is absorbed and ferric form are not absorbed
(b) Ascorbic acid (Vitamin C) increases the absorption of iron (c) The interfering substances such as phytic acid and oxalic acid decreases absorption of iron
Regulation of absorption of Iron
Absorption of iron is regulated by three main mechanisms, which includes
(a) Mucosal Regulation
(b) Storer regulation
(c) Erythropoietic regulation
In mucosal regulation absorption of iron requires DM-1 and ferroportin. Both the proteins are down regulated by hepcidin secreted by liver. The above regulation occurs when the body irons reserves are adequate. When the body iron content gets felled, storer regulation takes place. In storer regulation the mucosal is signaled for increase in iron absorption. The erythropoietic regulation occurs in response to anemia. Here the erythroid cells will signal the mucosa to increase the iron absorption.
Iron transport in blood
The transport form of iron in blood is transferin. Transferin are glycoprotein secreted by liver. In blood, the ceruloplasmin is the ferroxidase which oxidizes ferrous to ferric state.
Storage form of iron is ferritin. Almost no iron is excreted through urine.
Anemia
Anemia is the most common nutritional deficiency disease. The microscopic appearance of anemia is characterized by microcytic hypochromic anemia
The abnormal gene responsible for hemosiderosis is located on the short arm of chromosome No.6.
The main causes of iron deficiency or anemia are
(a) Nutritional deficiency of iron (b) Lack of iron absorption (c) Hook worm infection (d) Repeated pregnancy (e) Chronic blood loss (f) Nephrosis (g) Lead poisoning
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.