NEET MDS Lessons
Biochemistry
- There are two important phospholipids, Phosphatidylcholine and Phosphatidylserine found the cell membrane without which cell cannot function normally.
- Phospholipids are also important for optimal brain health as they found the cell membrane of brain cells also which help them to communicate and influence the receptors function. That is the reason food stuff which is rich in phospholipids like soy, eggs and the brain tissue of animals are good for healthy and smart brain.
- Phospholipids are the main component of cell membrane or plasma membrane. The bilayer of phospholipid molecules determine the transition of minerals, nutrients, and drugs in and out of the cell and affect various functions of them.
- As phospholipids are main component of all cell membrane, they influence a number of organs and tissues, such as the heart, blood cells and the immune system. As we grown up the amount of phospholipids decreases and reaches to decline.
- Phospholipids present in cell membrane provide cell permeability and flexibility with various substances as well its ability to move fluently. The arrangement of phospholipid molecules in lipid bilayer prevent amino acids, carbohydrates, nucleic acids, and proteins from moving across the membrane by diffusion. The lipid bi-layer is usually help to prevent adjacent molecules from sticking to each other.
- The selectivity of cell membrane form certain substances are due to the presence of hydrophobic and hydrophilic part molecules and their arrangement in bilayer. This bilayer is also maintained the normal pH of cell to keeps it functioning properly.
- Phospholipids are also useful in the treatment of memory problem associated with chronic substances as they improve the ability of organism to adapt the chronic stress.
Vitamin B12: Cobalamin
Vitamin B12, also known as cobalamin, aids in the building of genetic material, production of normal red blood cells, and maintenance of the nervous system.
RDA The Recommended Dietary Allowance (RDA) for vitamin B12 is 2.4 mcg/day for adult males and females
Vitamin B12 Deficiency
Vitamin B12 deficiency most commonly affects strict vegetarians (those who eat no animal products), infants of vegan mothers, and the elderly. Symptoms of deficiency include anemia, fatigue, neurological disorders, and degeneration of nerves resulting in numbness and tingling.
Pantothenic Acid
Pantothenic Acid is involved in energy production, and aids in the formation of hormones and the metabolism of fats, proteins, and carbohydrates from food.
RDA The Adequate Intake (AI) for Pantothenic Acid is 5 mg/day for both adult males and females.
Pantothenic Acid Deficiency
Pantothenic Acid deficiency is uncommon due to its wide availability in most foods.
Glucagon
Glucagon, a peptide hormone synthesized and secreted from the α-cells of the islets of Langerhans of pancreas, raises blood glucose levels. The pancreas releases glucagon when blood sugar (glucose) levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is released into the bloodstream. Glucagon and insulin are part of a feedback system that keeps blood glucose levels at a stable level.
Regulation and function
Secretion of glucagon is stimulated by hypoglycemia, epinephrine, arginine, alanine, acetylcholine, and cholecystokinin.
Secretion of glucagon is inhibited by somatostatin, insulin, increased free fatty acids and keto acids into the blood, and increased urea production.
Role of Coenzymes
The functional role of coenzymes is to act as transporters of chemical groups from one reactant to another.
Ex. The hydride ion (H+ + 2e-) carried by NAD or the mole of hydrogen carried by FAD;
The amine (-NH2) carried by pyridoxal phosphate
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
Acyl-CoA Synthases (Thiokinases), associated with endoplasmic reticulum membranes and the outer mitochondrial membrane, catalyze activation of long chain fatty acids, esterifying them to coenzyme A, as shown at right. This process is ATP-dependent, and occurs in 2 steps. There are different Acyl-CoA Synthases for fatty acids of different chain lengths.
Exergonic hydrolysis of PPi (P~P), catalyzed by Pyrophosphatase, makes the coupled reaction spontaneous. Overall, two ~P bonds of ATP are cleaved during fatty acid activation. The acyl-coenzyme A product includes one "high energy" thioester linkage.
Summary of fatty acid activation:
- fatty acid + ATP → acyl-adenylate + PPi
PPi → Pi - acyladenylate + HS-CoA → acyl-CoA + AMP
Overall: fatty acid + ATP + HS-CoA → acyl-CoA + AMP + 2 Pi
For most steps of the b-Oxidation Pathway, there are multiple enzymes specific for particular fatty acid chain lengths.
Fatty acid b-oxidation is considered to occur in the mitochondrial matrix. Fatty acids must enter the matrix to be oxidized. However enzymes of the pathway specific for very long chain fatty acids are associated with the inner mitochondrial membrane (facing the matrix).
Fatty acyl-CoA formed outside the mitochondria can pass through the outer mitochondrial membrane, which contains large VDAC channels, but cannot penetrate the mitochondrial inner membrane.
Transfer of the fatty acid moiety across the inner mitochondrial membrane involves carnitine.
Carnitine Palmitoyl Transferases catalyze transfer of a fatty acid between the thiol of Coenzyme A and the hydroxyl on carnitine.
Carnitine-mediated transfer of the fatty acyl moiety into the mitochondrial matrix is a 3-step process, as presented below.
- Carnitine Palmitoyl Transferase I, an enzyme associated with the cytosolic surface of the outer mitochondrial membrane, catalyzes transfer of a fatty acid from ester linkage with the thiol of coenzyme A to the hydroxyl on carnitine.
- Carnitine Acyltransferase, an antiporter in the inner mitochondrial membrane, mediates transmembrane exchange of fatty acyl-carnitine for carnitine.
- Within the mitochondrial matrix (or associated with the matrix surface of the inner mitochondrial membrane, Carnitine Palmitoyl Transferase II catalyzes transfer of the fatty acid from carnitine to coenzyme A. (Carnitine exits the matrix in step 2.) The fatty acid is now esterified to coenzyme A within the mitochondrial matrix
Control of fatty acid oxidation is exerted mainly at the step of fatty acid entry into mitochondria.
Malonyl-CoA inhibits Carnitine Palmitoyl Transferase I. (Malonyl-CoA is also a precursor for fatty acid synthesis). Malonyl-CoA is produced from acetyl-CoA by the enzyme Acetyl-CoA Carboxylase
AMP-Activated Kinase, a sensor of cellular energy levels, catalyzes phosphorylation of Acetyl-CoA Carboxylase under conditions of high AMP (when ATP is low). Phosphorylation inhibits Acetyl-CoA Carboxylase, thereby decreasing malonyl-CoA production.
The decrease in malonyl-CoA concentration releases Carnitine Palmitoyl Transferase I from inhibition. The resulting increase in fatty acid oxidation generates acetyl-CoA for entry into Krebs cycle, with associated production of ATP