NEET MDS Lessons
Biochemistry
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
The input to fatty acid synthesis is acetyl-CoA, which is carboxylated to malonyl-CoA.
The ATP-dependent carboxylation provides energy input. The CO2 is lost later during condensation with the growing fatty acid. The spontaneous decarboxylation drives the condensation.
fatty acid synthesis
acetyl-CoA + 7 malonyl-CoA + 14 NADPH → palmitate + 7 CO2 + 14 NADP+ + 8 CoA
ATP-dependent synthesis of malonate:
8 acetyl-CoA + 14 NADPH + 7 ATP → palmitate + 14 NADP+ + 8 CoA + 7 ADP + 7 Pi
Fatty acid synthesis occurs in the cytosol. Acetyl-CoA generated in the mitochondria is transported to the cytosol via a shuttle mechanism involving citrate
Sugar derivatives
Sugar alcohol - lacks an aldehyde or ketone. An example is ribitol.
Sugar acid - the aldehyde at C1, or the hydroxyl on the terminal carbon, is oxidized to a carboxylic acid. Examples are gluconic acid and glucuronic acid
Amino sugar - an amino group substitutes for one of the hydroxyls. An example is glucosamine. The amino group may be acetylated.
N-acetylneuraminate, (N-acetylneuraminic acid, also called sialic acid) is often found as a terminal residue of oligosaccharide chains of glycoproteins. Sialic acid imparts negative charge to glycoproteins, because its carboxyl group tends to dissociate a proton at physiological pH.
Glycosidic bonds: The anomeric hydroxyl group and a hydroxyl group of another sugar or some other compound can join together, splitting out water to form a glycosidic bond.
R-OH + HO-R' → R-O-R' + H2O
Disaccharides: Maltose, a cleavage product of starch, is a disaccharide with an α (1→4) glycosidic linkage between the C1 hydroxyl of one glucose and the C4 hydroxyl of a second glucose. Maltose is the α anomer, because the O at C1 points down from the ring.
Cellobiose, a product of cellulose breakdown, is the otherwise equivalent β anomer. The configuration at the anomeric C1 is β (O points up from the ring). The β(1→4) glycosidic linkage is represented as a "zig-zag" line, but one glucose residue is actually flipped over relative to the other.
Other disaccharides
- Sucrose, common table sugar, has a glycosidic bond linking the anomeric hydroxyls of glucose and fructose. Because the configuration at the anomeric carbon of glucose is α (O points down from the ring), the linkage is designated α (1→2). The full name is α -D-glucopyranosyl-(1→2) β -D- fructopyranose.
- Lactose, milk sugar, is composed of glucose and galactose with β (→4) linkage → the anomeric hydroxyl of galactose. Its full name is β -D-galactopyranosyl-(1→)- α -D-glucopyranose
Polysaccharides:
Plants store glucose as amylose or amylopectin, glucose polymers collectively called starch. Glucose storage in polymeric form minimizes osmotic effects
Amylose is a glucose polymer with α (1→4) glycosidic linkages, as represented above. The end of the polysaccharide with an anomeric carbon (C1) that is not involved in a glycosidic bond is called the reducing end
Amylopectin is a glucose polymer with mainly α (1→4) linkages, but it also has branches formed by α (1→6) linkages. The branches are generally longer than shown above. The branches produce a compact structure, and provide multiple chain ends at which enzymatic cleavage of the polymer can occur.
Glycogen, the glucose storage polymer in animals, is similar in structure to amylopectin. But glycogen has more α (1→6) branches. The highly branched structure permits rapid release of glucose from glycogen stores, e.g., in muscle cells during exercise. The ability to rapidly mobilize glucose is more essential to animals than to plants.
Cellulose, a major constituent of plant cell walls, consists of long linear chains of glucose, with β (1→4) linkages. Every other glucose in cellulose is flipped over, due to the β linkages. This promotes intrachain and interchain hydrogen bonds, as well as van der Waals interactions, that cause cellulose chains to be straight and rigid, and pack with a crystalline arrangement in thick bundles called microfibrils.
Glycosaminoglycans (mucopolysaccharides) are polymers of repeating disaccharides. Within the disaccharides, the sugars tend to be modified, with acidic groups, amino groups, sulfated hydroxyl and amino groups, etc. Glycosaminoglycans tend to be negatively charged, because of the prevalence of acidic groups.
Hyaluronate is a glycosaminoglycan with a repeating disaccharide consisting of two glucose derivatives, glucuronate (glucuronic acid) and N-acetylglucosamine. The glycosidic linkages are β(1→3) and β(1→4).
When covalently linked to specific core proteins, glycosaminoglycans form complexes called proteoglycans. Some proteoglycans of the extracellular matrix in turn link non-covalently to hyaluronate via protein domains called link modules. For example, in cartilage multiple copies of the aggrecan proteoglycan bind to an extended hyaluronate backbone to form a large complex Versican, another proteoglycan that binds to hyaluronate, is in the extracellular matrix of loose connective tissues.
Heparan sulfate is initially synthesized on a membrane-embedded core protein as a polymer of alternating glucuronate and N-acetylglucosamine residues. Later, in segments of the polymer, glucuronate residues may be converted to a sulfated sugar called iduronic acid, while N-acetylglucosamine residues may be deacetylated and/or sulfated
Heparin, a glycosaminoglycan found in granules of mast cells, has a structure similar to that of heparan sulfates, but is relatively highly sulfated.
Some cell surface heparan sulfate glycosaminoglycans remain covalently linked to core proteins embedded in the plasma membrane. Proteins involved in signaling and adhesion at the cell surface have been identified that recognize and bind segments of heparan sulfate chains having particular patterns of sulfation
Lectins are glycoproteins that recognize and bind to specific oligosaccharides.
- Concanavalin A and wheat germ agglutinin are plant lectins that have been useful research tools
- Mannan-binding lectin (MBL) is a glycoprotein found in blood plasma. It associates with cell surface carbohydrates of disease-causing microorganisms, promoting phagocytosis of these organisms as part of the immune response.
- Selectins are integral proteins of the plasma membrane with lectin-like domains that protrude on the outer surface of mammalian cells. Selectins participate in cell-cell recognition and binding.
The Hemoglobin Buffer Systems
These buffer systems are involved in buffering CO2 inside erythrocytes. The buffering capacity of hemoglobin depends on its oxygenation and deoxygenation. Inside the erythrocytes, CO2 combines with H2O to form carbonic acid (H2CO3) under the action of carbonic anhydrase.
At the blood pH 7.4, H2CO3 dissociates into H+ and HCO3 − and needs immediate buffering.
| Enzyme | Clinical Use | Indicates |
|---|---|---|
| ALT (SGPT) | Specific to liver injury | Hepatitis, liver necrosis |
| AST (SGOT) | Found in liver, heart, muscle | Liver disease, myocardial infarction |
| ALP | Bile duct obstruction, bone disease | Cholestasis, bone metastases |
| GGT | Alcoholic liver disease, biliary obstruction | Alcohol abuse, hepatobiliary disease |
| LDH | Non-specific, elevated in many conditions | Liver, cardiac, or hemolytic disorders |
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.
The pH scale
An acidic solution is one in which [H+ ] > [OH- ]
•In an acidic solution, [H+ ] > 10-7 , pH < 7.
•A basic solution is when [OH- ] > [H+ ].
•In a basic solution, [OH- ] > 10-7 , pOH < 7, and pH >7.
• When the pH = 7, the solution is neutral.
•Physiological pH range is 6.5 to 8.0