NEET MDS Lessons
Biochemistry
Ampholytes, Polyampholytes, pI and Zwitterion
Many substances in nature contain both acidic and basic groups as well as many different types of these groups in the same molecule. (e.g. proteins). These are called ampholytes (one acidic and one basic group) or polyampholytes (many acidic and basic groups). Proteins contains many different amino acids some of which contain ionizable side groups, both acidic and basic. Therefore, a useful term for dealing with the titration of ampholytes and polyampholytes (e.g. proteins) is the isoelectric point, pI. This is described as the pH at which the effective net charge on a molecule is zero.
For the case of a simple ampholyte like the amino acid glycine the pI, when calculated from the Henderson-Hasselbalch equation, is shown to be the average of the pK for the a-COOH group and the pK for the a-NH2 group:
pI = [pKa-(COOH) + pKa-(NH3+)]/2
For more complex molecules such as polyampholytes the pI is the average of the pKa values that represent the boundaries of the zwitterionic form of the molecule. The pI value, like that of pK, is very informative as to the nature of different molecules. A molecule with a low pI would contain a predominance of acidic groups, whereas a high pI indicates predominance of basic groups.
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
Regulation of PTH secretion
Secretion of parathyroid hormone is controlled chiefly by serum [Ca2+] through negative feedback. Calcium-sensing receptors located on parathyroid cells are activated when [Ca2+] is low.
Hypomagnesemia inhibits PTH secretion and also causes resistance to PTH, leading to a form of hypoparathyroidism that is reversible.
Hypermagnesemia also results in inhibition of PTH secretion.
Stimulators of PTH includes decreased serum [Ca2+], mild decreases in serum [Mg2+], and an increase in serum phosphate.
Inhibitors include increased serum [Ca2+], severe decreases in serum [Mg2+], which also produces symptoms of hypoparathyroidism (such as hypocalcemia), and calcitriol.
Glycogen Storage Diseases are genetic enzyme deficiencies associated with excessive glycogen accumulation within cells.
- When an enzyme defect affects mainly glycogen storage in liver, a common symptom is hypoglycemia (low blood glucose), relating to impaired mobilization of glucose for release to the blood during fasting.
- When the defect is in muscle tissue, weakness and difficulty with exercise result from inability to increase glucose entry into Glycolysis during exercise.
Various type of Glycogen storage disease are
|
Type |
Name |
Enzyme Deficient |
|
I |
Von Geirke’s Disease |
Glucose -6-phosphate |
|
II |
Pompe’s Disease |
(1, 4)glucosidase |
|
III |
Cori’s Disease |
Debranching Enzymes |
|
IV |
Andersen’s Disease |
Branching Enzymes |
|
V |
McArdle’s Disease |
Muscles Glycogen Phosphorylase |
Nomenclature for stereoisomers: D and L designations are based on the configuration about the single asymmetric carbon in glyceraldehydes
For sugars with more than one chiral center, the D or L designation refers to the asymmetric carbon farthest from the aldehyde or keto group.
Most naturally occurring sugars are D isomers.
D & L sugars are mirror images of one another. They have the same name. For example, D-glucose and L-glucose
Other stereoisomers have unique names, e.g., glucose, mannose, galactose, etc. The number of stereoisomers is 2 n, where n is the number of asymmetric centers. The six-carbon aldoses have 4 asymmetric centers, and thus 16 stereoisomers (8 D-sugars and 8 L-sugars
An aldehyde can react with an alcohol to form a hemiacetal
Similarly a ketone can react with an alcohol to form a hemiketal
Pentoses and hexoses can cyclize, as the aldehyde or keto group reacts with a hydroxyl on one of the distal carbons
E.g., glucose forms an intra-molecular hemiacetal by reaction of the aldehyde on C1 with the hydroxyl on C5, forming a six-member pyranose ring, named after the compound pyran
The representations of the cyclic sugars below are called Haworth projections.
Fructose can form either:
- a six-member pyranose ring, by reaction of the C2 keto group with the hydroxyl on C6
- a 5-member furanose ring, by reaction of the C2 keto group with the hydroxyl on C5.
Cyclization of glucose produces a new asymmetric center at C1, with the two stereoisomers called anomers, α & β
Haworth projections represent the cyclic sugars as having essentially planar rings, with the OH at the anomeric C1 extending either:
- below the ring (α)
- above the ring (β).
Because of the tetrahedral nature of carbon bonds, the cyclic form of pyranose sugars actually assume a "chair" or "boat" configuration, depending on the sugar
Titration of a weak acid with a strong base
• A weak acid is mostly in its conjugate acid form
• When strong base is added, it removes protons from the solution, more and more acid is in the conjugate base form, and the pH increases
• When the moles of base added equals half the total moles of acid, the weak acid and its conjugate base are in equal amounts. The ratio of CB / WA = 1 and according to the HH equation, pH = pKa + log(1) or pH = pKa.
• If more base is added, the conjugate base form becomes greater till the equivalance point when all of the acid is in the conjugate base form.
Glycogen Metabolism
The formation of glycogen from glucose is called Glycogenesis
Glycogen is a polymer of glucose residues linked mainly by a(1→ 4) glycosidic linkages. There are a(1→6) linkages at branch points. The chains and branches are longer than shown. Glucose is stored as glycogen predominantly in liver and muscle cells
Glycogen Synthesis
Uridine diphosphate glucose (UDP-glucose) is the immediate precursor for glycogen synthesis. As glucose residues are added to glycogen, UDP-glucose is the substrate and UDP is released as a reaction product. Nucleotide diphosphate sugars are precursors also for synthesis of other complex carbohydrates, including oligosaccharide chains of glycoproteins, etc.
UDP-glucose is formed from glucose-1-phosphate and uridine triphosphate (UTP)
glucose-1-phosphate + UTP → UDP-glucose + 2 Pi
Cleavage of PPi is the only energy cost for glycogen synthesis (1P bond per glucose residue)
Glycogenin initiates glycogen synthesis. Glycogenin is an enzyme that catalyzes glycosylation of one of its own tyrosine residues.
Physiological regulation of glycogen metabolism
Both synthesis and breakdown of glycogen are spontaneous. If glycogen synthesis and phosphorolysis were active simultaneously in a cell, there would be a futile cycle with cleavage of 1 P bond per cycle
To prevent such a futile cycle, Glycogen Synthase and Glycogen Phosphorylase are reciprocally regulated, both by allosteric effectors and by covalent modification (phosphorylation)
Glycogen catabolism (breakdown)
Glycogen Phosphorylase catalyzes phosphorolytic cleavage of the →(1→4) glycosidic linkages of glycogen, releasing glucose-1-phosphate as the reaction product.
Glycogen (n residues) + Pi → glycogen (n-1 residues) + glucose-1-phosphate
The Major product of glycogen breakdown is glucose -1-phosphate
Fate of glucose-1-phosphate in relation to other pathways:
Phosphoglucomutase catalyzes the reversible reaction:
Glucose-1-phosphate → Glucose-6-phosphate