NEET MDS Lessons
Biochemistry
Amino Acid Biosynthesis
Glutamate and Aspartate
Glutamate and aspartate are synthesized from their widely distributed a-keto acid precursors by simple 1-step transamination reactions. The former catalyzed by glutamate dehydrogenase and the latter by aspartate aminotransferase, AST. Aspartate is also derived from asparagine through the action of asparaginase. The importance of glutamate as a common intracellular amino donor for transamination reactions and of aspartate as a precursor of ornithine for the urea cycle is described in the Nitrogen Metabolism page.
Alanine and the Glucose-Alanine Cycle
Role in protein synthesis,
Alanine is second only to glutamine in prominence as a circulating amino acid.. When alanine transfer from muscle to liver is coupled with glucose transport from liver back to muscle, the process is known as the glucose-alanine cycle. The key feature of the cycle is that in 1 molecule, alanine, peripheral tissue exports pyruvate and ammonia (which are potentially rate-limiting for metabolism) to the liver, where the carbon skeleton is recycled and most nitrogen eliminated.
There are 2 main pathways to production of muscle alanine: directly from protein degradation, and via the transamination of pyruvate by alanine transaminase, ALT (also referred to as serum glutamate-pyruvate transaminase, SGPT).
glutamate + pyruvate <-------> a-KG + alanine
Cysteine Biosynthesis
The sulfur for cysteine synthesis comes from the essential amino acid methionine. A condensation of ATP and methionine catalyzed by methionine adenosyltransferase yields S-adenosylmethionine
Tyrosine Biosynthesis
Tyrosine is produced in cells by hydroxylating the essential amino acid phenylalanine. This relationship is much like that between cysteine and methionine. Half of the phenylalanine required goes into the production of tyrosine; if the diet is rich in tyrosine itself, the requirements for phenylalanine are reduced by about 50%.
Phenylalanine hydroxylase is a mixed-function oxygenase: one atom of oxygen is incorporated into water and the other into the hydroxyl of tyrosine. The reductant is the tetrahydrofolate-related cofactor tetrahydrobiopterin, which is maintained in the reduced state by the NADH-dependent enzyme dihydropteridine reductase (DHPR).
Ornithine and Proline Biosynthesis
Glutamate is the precursor of both proline and ornithine, with glutamate semialdehyde being a branch point intermediate leading to one or the other of these 2 products. While ornithine is not one of the 20 amino acids used in protein synthesis, it plays a significant role as the acceptor of carbamoyl phosphate in the urea cycle
Serine Biosynthesis
The main pathway to serine starts with the glycolytic intermediate 3-phosphoglycerate. An NADH-linked dehydrogenase converts 3-phosphoglycerate into a keto acid, 3-phosphopyruvate, suitable for subsequent transamination. Aminotransferase activity with glutamate as a donor produces 3-phosphoserine, which is converted to serine by phosphoserine phosphatase.
Glycine Biosynthesis
The main pathway to glycine is a 1-step reaction catalyzed by serine hydroxymethyltransferase. This reaction involves the transfer of the hydroxymethyl group from serine to the cofactor tetrahydrofolate (THF), producing glycine and N5,N10-methylene-THF. Glycine produced from serine or from the diet can also be oxidized by glycine cleavage complex, GCC, to yield a second equivalent of N5,N10-methylene-tetrahydrofolate as well as ammonia and CO2.
Glycine is involved in many anabolic reactions other than protein synthesis including the synthesis of purine nucleotides, heme, glutathione, creatine and serine.
Aspartate/Asparagine and Glutamate/Glutamine Biosynthesis
Glutamate is synthesized by the reductive amination of a-ketoglutarate catalyzed by glutamate dehydrogenase; it is thus a nitrogen-fixing reaction. In addition, glutamate arises by aminotransferase reactions, with the amino nitrogen being donated by a number of different amino acids. Thus, glutamate is a general collector of amino nitrogen.
Aspartate is formed in a transamintion reaction catalyzed by aspartate transaminase, AST. This reaction uses the aspartate a-keto acid analog, oxaloacetate, and glutamate as the amino donor. Aspartate can also be formed by deamination of asparagine catalyzed by asparaginase.
Asparagine synthetase and glutamine synthetase, catalyze the production of asparagine and glutamine from their respective a-amino acids. Glutamine is produced from glutamate by the direct incorporation of ammonia; and this can be considered another nitrogen fixing reaction. Asparagine, however, is formed by an amidotransferase reaction.
Aminotransferase reactions are readily reversible. The direction of any individual transamination depends principally on the concentration ratio of reactants and products. By contrast, transamidation reactions, which are dependent on ATP, are considered irreversible. As a consequence, the degradation of asparagine and glutamine take place by a hydrolytic pathway rather than by a reversal of the pathway by which they were formed. As indicated above, asparagine can be degraded to aspartate
MAGNESIUM
The normal serum level of Magnesium is 1.8 to 2.2. mg/dl.
Functions of Magnesium
(a) Irritability of neuromuscular tissues is lowered by Magnesium
(b) Magnesium deficiency leads to decrease in Insulin dependent uptake of glucose
(c) Magnesium supplementation improves glucose tolerance
Causes such as liver cirrhosis, protein calorie malnutrition and hypo para thyroidism leads to hypomagnesemia
The main causes of hypermagnesemia includes renal failure, hyper para thyroidism, rickets, oxalate poisoning and multiple myeloma.
FATTY ACIDS
Fatty acids consist of a hydrocarbon chain with a carboxylic acid at one end.
• are usually in esterified form as major components of other lipids
• are often complexed in triacylglycerols (TAGs)
• most have an even number of carbon atoms (usually 14 to 24)
• are synthesized by concatenation of C2 units.
• C16 & C18 FAs are the most common FAs in higher plants and animals
• Are either:
—saturated (all C-C bonds are single bonds) or
—unsaturated (with one or more double bonds in the chain)
—monounsaturated (a single double bond)
1.Example of monounsaturated FA: Oleic acid 18:1(9) (the number in unsaturated FA parentheses indicates that the double bond is between carbons 9 & 10)
2. Double bonds are almost all in the cis conformation
—polyunsaturated (more then one double bond)
Polyunsaturated fatty acids contain 2 or more double bonds. They usually occur at every third carbon atom towards the methyl terminus (-CH3 ) of the molecule. Example of polyunsaturated FA: Linoleic acid 18:2(9,12)
• the number of double bonds in FAs varies from 1 to 4 (usually), but in most bacteria it is rarely more than 1
Saturated FAs are highly flexible molecules that can assume a wide range of conformations because there is relatively free rotation about their C-C bonds.
The basic characteristics of enzymes includes
(i) Almost all the enzymes are proteins and they follow the physical and chemical reactions of proteins (ii) Enzymes are sensitive and labile to heat
(iii) Enzymes are water soluble
(iv) Enzymes could be precipitated by protein precipitating agents such as ammonium sulfate and trichloroacetic acid.
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.
IONIZATION OF WATER, WEAK ACIDS AND WEAK BASES
The ionization of water can be described by an equilibrium constant. When weak acids or weak bases are dissolved in water, they can contribute H+ by ionizing (if acids) or consume H+ by being protonated (if bases). These processes are also governed by equilibrium constants
Water molecules have a slight tendency to undergo reversible ionization to yield a hydrogen ion and a hydroxide ion :
H2O = H+ + OH−
The position of equilibrium of any chemical reaction is given by its equilibrium constant. For the general reaction,
A+B = C + D
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
