NEET MDS Lessons
Biochemistry
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
Amino Acid Catabolism
Glutamine/Glutamate and Asparagine/Aspartate Catabolism
Glutaminase is an important kidney tubule enzyme involved in converting glutamine (from liver and from other tissue) to glutamate and NH3+, with the NH3+ being excreted in the urine. Glutaminase activity is present in many other tissues as well, although its activity is not nearly as prominent as in the kidney. The glutamate produced from glutamine is converted to a-ketoglutarate, making glutamine a glucogenic amino acid.
Asparaginase is also widely distributed within the body, where it converts asparagine into ammonia and aspartate. Aspartate transaminates to oxaloacetate, which follows the gluconeogenic pathway to glucose.
Glutamate and aspartate are important in collecting and eliminating amino nitrogen via glutamine synthetase and the urea cycle, respectively. The catabolic path of the carbon skeletons involves simple 1-step aminotransferase reactions that directly produce net quantities of a TCA cycle intermediate. The glutamate dehydrogenase reaction operating in the direction of a-ketoglutarate production provides a second avenue leading from glutamate to gluconeogenesis.
Alanine Catabolism
Alanine is also important in intertissue nitrogen transport as part of the glucose-alanine cycle. Alanine's catabolic pathway involves a simple aminotransferase reaction that directly produces pyruvate. Generally pyruvate produced by this pathway will result in the formation of oxaloacetate, although when the energy charge of a cell is low the pyruvate will be oxidized to CO2 and H2O via the PDH complex and the TCA cycle. This makes alanine a glucogenic amino acid.
Arginine, Ornithine and Proline Catabolism
The catabolism of arginine begins within the context of the urea cycle. It is hydrolyzed to urea and ornithine by arginase.
Ornithine, in excess of urea cycle needs, is transaminated to form glutamate semialdehyde. Glutamate semialdehyde can serve as the precursor for proline biosynthesis as described above or it can be converted to glutamate.
Proline catabolism is a reversal of its synthesis process.
The glutamate semialdehyde generated from ornithine and proline catabolism is oxidized to glutamate by an ATP-independent glutamate semialdehyde dehydrogenase. The glutamate can then be converted to α-ketoglutarate in a transamination reaction. Thus arginine, ornithine and proline, are glucogenic.
Methionine Catabolism
The principal fates of the essential amino acid methionine are incorporation into polypeptide chains, and use in the production of α -ketobutyrate and cysteine via SAM as described above. The transulfuration reactions that produce cysteine from homocysteine and serine also produce α -ketobutyrate, the latter being converted to succinyl-CoA.
Regulation of the methionine metabolic pathway is based on the availability of methionine and cysteine
Phenylalanine and Tyrosine Catabolism
Phenylalanine normally has only two fates: incorporation into polypeptide chains, and production of tyrosine via the tetrahydrobiopterin-requiring phenylalanine hydroxylase. Thus, phenylalanine catabolism always follows the pathway of tyrosine catabolism. The main pathway for tyrosine degradation involves conversion to fumarate and acetoacetate, allowing phenylalanine and tyrosine to be classified as both glucogenic and ketogenic.
Tyrosine is equally important for protein biosynthesis as well as an intermediate in the biosynthesis of several physiologically important metabolites e.g. dopamine, norepinephrine and epinephrine
Enzymes are protein catalyst produced by a cell and responsible ‘for the high rate’ and specificity of one or more intracellular or extracellular biochemical reactions.
Enzymes are biological catalysts responsible for supporting almost all of the chemical reactions that maintain animal homeostasis. Enzyme reactions are always reversible.
The substance, upon which an enzyme acts, is called as substrate. Enzymes are involved in conversion of substrate into product.
Almost all enzymes are globular proteins consisting either of a single polypeptide or of two or more polypeptides held together (in quaternary structure) by non-covalent bonds. Enzymes do nothing but speed up the rates at which the equilibrium positions of reversible reactions are attained.
In terms of thermodynamics, enzymes reduce the activation energies of reactions, enabling them to occur much more readily at low temperatures - essential for biological systems.
Gluconeogenesis
It is the process by which Glucose or glycogen is formed from non carbohydrate substances.
Gluconeogenesis occurs mainly in liver.
Gluconeogenesis inputs:
The source of pyruvate and oxaloacetate for gluconeogenesis during fasting or carbohydrate starvation is mainly amino acid catabolism. Some amino acids are catabolized to pyruvate, oxaloacetate, Muscle proteins may break down to supply amino acids. These are transported to liver where they are deaminated and converted to gluconeogenesis inputs.
Glycerol, derived from hydrolysis of triacylglycerols in fat cells, is also a significant input to gluconeogenesis
Glycolysis & Gluconeogenesis pathways are both spontaneous If both pathways were simultaneously active within a cell it would constitute a "futile cycle" that would waste energy
Glycolysis yields 2~P bonds of ATP.
Gluconeogenesis expends 6~P bonds of ATP and GTP.
A futile cycle consisting of both pathways would waste 4 P.bonds per cycle.To prevent this waste, Glycolysis and Gluconeogenesis pathways are reciprocally regulated.
PHOSPHOLIPIDS
These are complex or compound lipids containing phosphoric acid, in addition to fatty acids, nitrogenous base and alcohol
There are two classes of phospholipids
1. Glycerophospholipids (or phosphoglycerides) that contain glycerol as the alcohol.
2. Sphingophospholipids (or sphingomyelins) that contain sphingosine as the alcohol
Glycerophospholipids
Glycerophospholipids are the major lipids that occur in biological membranes. They consist of glycerol 3-phosphate esterified at its C1 and C2 with fatty acids. Usually, C1 contains a saturated fatty acid while C2 contains an unsaturated fatty acid.
In glycerophospholipids, we refer to the glycerol residue (highlighted red above) as the "glycerol backbone."
Glycerophospholipids are Amphipathic
Glycerophospholipids are sub classified as
1. Phosphatidylethanolamine or cephalin also abbreviated as PE is found in biological membranes and composed of ethanolamine bonded to phosphate group on diglyceride.
2. Phosphatidylcholine or lecithin or PC which has chloline bonded with phosphate group and glycerophosphoric acid with different fatty acids like palmitic or hexadecanoic acid, margaric acid, oleic acid. It is a major component of cell membrane and mainly present in egg yolk and soy beans.
3. Phosphatidic acid (phosphatidate) (PA)
It consists of a glycerol with one saturated fatty acid bonded to carbon-1 of glycerol and an unsaturated fatty acid bonded to carbon-2 with a phosphate group bonded to carbon-3.
4.Phosphatidylserine (PS)
This phospholipid contains serine as an organic compound with other main components of phospholipids. Generally it found on the cytosolic side of cell membranes.
5. Phosphoinositides
It is a group of phospholipids which are negatively charged and act as a a minor component in the cytosolic side of eukaryotic cell membranes. On the basis of different number of phosphate groups they can be different types like phosphatidylinositol phosphate (PIP), phosphatidylinositol bisphosphate(PIP2) and phosphatidylinositol trisphosphate (PIP3). PIP, PIP2 and PIP3 and collectively termed as phosphoinositide.
6. Cardiolipin :
lt is so named as it was first isolated from heart muscle. Structurally, a cardiolipin consists of two molecules of phosphatidic acid held by an additional glycerol through phosphate groups. lt is an important component of inner mitochondrial membrane. Cardiolipin is the only phosphoglyceride that possesses antigenic properties.
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 |
LIPOPROTIENS
Lipoproteins Consist of a Nonpolar Core & a Single Surface Layer of Amphipathic Lipids
The nonpolar lipid core consists of mainly triacylglycerol and cholesteryl ester and is surrounded by a single surface layer of amphipathic phospholipid and cholesterol molecules .These are oriented so that their polar groups face outward to the aqueous medium. The protein moiety of a lipoprotein is known as an apolipoprotein or apoprotein,constituting nearly 70% of some HDL and as little as 1% of Chylomicons. Some apolipoproteins are integral and cannot be removed, whereas others can be freely transferred to other lipoproteins.
There re five types of lipoproteins, namely chylomicrons, very low density lipoproteins(VLDL) low density lipoproteins (LDL), high density Lipoproteins (HDL) and free fatty acid-albumin complexes.