NEET MDS Lessons
Biochemistry
3-D Structure of proteins
Proteins are the main players in the life of a cell. Each protein is a unique sequence of amino acid residues, each of which folds into a unique, stable, three dimentional structure that is biologically functional.
Conformation = spatial arrangement of atoms that depends on rotation of bonds. Can change without breaking covalent bonds.
- Since each residue has a number of possible conformations, and there are many residues in a protein, the number of possible conformations for a protein is enormous.
Native conformation = single, stable shape a protein assumes under physiological conditions.
- In native conformation, rotation around covalent bonds in polypeptide is constrained by a number of factors ( H-bonding, weak interactions, steric interference)
- Biological function of proteins depends completely on its conformation. In biology, shape is everything.
- Proteins can be classified as globular or fibrous.
There are 4 levels of protein structure
- Primary structure
- linear sequence of amino acids
- held by covalent forces
- primary structure determines all oversall shape of folded polypeptides (i.e primary structure determines secondary , tertiary, and quaternary structures)
- Secondary structure
- regions of regularly repeating conformations of the peptide chain (α helices, β sheets)
- maintained by H-bonds between amide hydrogens and carbonyl oxygens of peptide backbone.
- Tertiary structure
- completely folded and compacted polypeptide chain.
- stabilized by interactions of sidechains of non-neighboring amino acid residues (fibrous proteins lack tertiary structure)
- Quaternary structure
- association of two or more polypeptide chains into a multisubunit protein.
SELENIUM
normal serum level is 50-100 mg/day
Selenium dependent enzymes include glutathione Peroxidase and 5-de-iodinase. Selenium concentration in testis is the highest in adult. It is very necessary for normal development and maturation of sperm.
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}
STEROIDS
Steroids are the compounds containing a cyclic steroid nucleus (or ring) namely cyclopentanoperhydrophenanthrene (CPPP).It consists of a phenanthrene nucleus (rings A, B and C) to which a cyclopentane ring (D) is attached.
Steroids are the compounds containing a cyclic steroid nucleus (or ring) namely cyclopentanoperhydrophenanthrene (CPPP).It consists of a phenanthrene nucleus (rings A, B and C) to which a cyclopentane ring (D) is attached.
There are several steroids in the biological system. These include cholesterol, bile acids, vitamin D, sex hormones, adrenocortical hormones,sitosterols, cardiac glycosides and alkaloids
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.
ISO-ENZYMES
Iso-enzymes are physically distinct forms of the same enzyme activity. Higher organisms have several physically distinct versions of a given enzyme, each of which catalyzes the same reaction. Isozymes arise through gene duplication and exhibit differences in properties such as sensitivity to particular regulatory factors or substrate affinity that adapts them to specific tissues or circumstances.
Isoforms of Lactate dehydrogenase is useful in diagnosis of myocardial infarction. While study of alkaline phosphatase isoforms are helpful in diagnosis of various bone disorder and obstructive liver diseases.
Erythrocytes and the Pentose Phosphate Pathway
The predominant pathways of carbohydrate metabolism in the red blood cell (RBC) are glycolysis, the PPP and 2,3-bisphosphoglycerate (2,3-BPG) metabolism (refer to discussion of hemoglobin for review of the synthesis and role role of 2,3-BPG).
Glycolysis provides ATP for membrane ion pumps and NADH for re-oxidation of methemoglobin. The PPP supplies the RBC with NADPH to maintain the reduced state of glutathione.
The inability to maintain reduced glutathione in RBCs leads to increased accumulation of peroxides, predominantly H2O2, that in turn results in a weakening of the cell wall and concomitant hemolysis.
Accumulation of H2O2 also leads to increased rates of oxidation of hemoglobin to methemoglobin that also weakens the cell wall.
Glutathione removes peroxides via the action of glutathione peroxidase.
The PPP in erythrocytes is essentially the only pathway for these cells to produce NADPH.
Any defect in the production of NADPH could, therefore, have profound effects on erythrocyte survival.