NEET MDS Lessons
Biochemistry
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
Keq, Kw and pH
As H2O is the medium of biological systems one must consider the role of this molecule in the dissociation of ions from biological molecules. Water is essentially a neutral molecule but will ionize to a small degree. This can be described by a simple equilibrium equation:
H2O <-------> H+ + OH-
This equilibrium can be calculated as for any reaction:
Keq = [H+][OH-]/[H2O]
Since the concentration of H2O is very high (55.5M) relative to that of the [H+] and [OH-], consideration of it is generally removed from the equation by multiplying both sides by 55.5 yielding a new term, Kw:
Kw = [H+][OH-]
This term is referred to as the ion product. In pure water, to which no acids or bases have been added:
Kw = 1 x 10-14 M2
As Kw is constant, if one considers the case of pure water to which no acids or bases have been added:
[H+] = [OH-] = 1 x 10-7 M
This term can be reduced to reflect the hydrogen ion concentration of any solution. This is termed the pH, where:
pH = -log[H+]
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.
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.
COENZYMES
Enzymes may be simple proteins, or complex enzymes.
A complex enzyme contains a non-protein part, called as prosthetic group (co-enzymes).
Coenzymes are heat stable low molecular weight organic compound. The combined form of protein and the co-enzyme are called as holo-enzyme. The heat labile or unstable part of the holo-enzyme is called as apo-enzyme. The apo-enzyme gives necessary three dimensional structures required for the enzymatic chemical reaction.
Co-enzymes are very essential for the biological activities of the enzyme.
Co-enzymes combine loosely with apo-enzyme and are released easily by dialysis. Most of the co-enzymes are derivatives of vitamin B complex
During fasting or carbohydrate starvation, oxaloacetate is depleted in liver because it is used for gluconeogenesis. This impedes entry of acetyl-CoA into Krebs cycle. Acetyl-CoA then is converted in liver mitochondria to ketone bodies, acetoacetate and b-hydroxybutyrate.
Three enzymes are involved in synthesis of ketone bodies:
b-Ketothiolase. The final step of the b-oxidation pathway runs backwards, condensing 2 acetyl-CoA to produce acetoacetyl-CoA, with release of one CoA.
HMG-CoA Synthase catalyzes condensation of a third acetate moiety (from acetyl-CoA) with acetoacetyl-CoA to form hydroxymethylglutaryl-CoA (HMG-CoA).
HMG-CoA Lyase cleaves HMG-CoA to yield acetoacetate plus acetyl-CoA.
b-Hydroxybutyrate Dehydrogenase catalyzes inter-conversion of the ketone bodies acetoacetate and b-hydroxybutyrate.
Ketone bodies are transported in the blood to other tissue cells, where they are converted back to acetyl-CoA for catabolism in Krebs cycle
Cori Cycle
The Cori Cycle operates during exercise, when aerobic metabolism in muscle cannot keep up with energy needs.
For a brief burst of ATP utilization, muscle cells utilize ~P stored as phosphocreatine. For more extended exercise, ATP is mainly provided by Glycolysis.
Lactate, produced from pyruvate, passes via the blood to the liver where it is converted to glucose. The glucose may travel back to the muscle to fuel Glycolysis.
The Cori Cycle costs 6 P in liver for every 2P made available in muscle. The net cost is 4 P Although costly in terms of "high energy" bonds, the Cori Cycle allows the organism to accommodate to large fluctuations in energy needs of skeletal muscle between rest and exercise.