NEET MDS Lessons
Biochemistry
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.
Step 1. Acyl-CoA Dehydrogenase catalyzes oxidation of the fatty acid moiety of acyl-CoA, to produce a double bond between carbon atoms 2 and 3.
There are different Acyl-CoA Dehydrogenases for short (4-6 C), medium (6-10 C), long and very long (12-18 C) chain fatty acids. Very Long Chain Acyl-CoA Dehydrogenase is bound to the inner mitochondrial membrane. The others are soluble enzymes located in the mitochondrial matrix.
FAD is the prosthetic group that functions as electron acceptor for Acyl-CoA Dehydrogenase.
A glutamate side-chain carboxyl extracts a proton from the a-carbon of the substrate, facilitating transfer of 2 e- with H+ (a hydride) from the b position to FAD. The reduced FAD accepts a second H+, yielding FADH2
The carbonyl oxygen of the thioester substrate is hydrogen bonded to the 2'-OH of the ribityl moiety of FAD, giving this part of FAD a role in positioning the substrate and increasing acidity of the substrate a-proton
The reactive glutamate and FAD are on opposite sides of the substrate at the active site. Thus the reaction is stereospecific, yielding a trans double bond in enoyl-CoA.
FADH2 of Acyl CoA Dehydrogenase is reoxidized by transfer of 2 electrons to an Electron Transfer Flavoprotein (ETF), which in turn passes the electrons to coenzyme Q of the respiratory chain.
Step 2. Enoyl-CoA Hydratase catalyzes stereospecific hydration of the trans double bond produced in the 1st step of the pathway, yielding L-hydroxyacyl-Coenzyme A
Step 3. Hydroxyacyl-CoA Dehydrogenase catalyzes oxidation of the hydroxyl in the b position (C3) to a ketone. NAD+ is the electron acceptor.
Step 4. b-Ketothiolase (b-Ketoacyl-CoA Thiolase) catalyzes thiolytic cleavage.
A cysteine S attacks the b-keto C. Acetyl-CoA is released, leaving the fatty acyl moiety in thioester linkage to the cysteine thiol. The thiol of HSCoA displaces the cysteine thiol, yielding fatty acyl-CoA (2 C shorter).
A membrane-bound trifunctional protein complex with two subunit types expresses the enzyme activities for steps 2-4 of the b-oxidation pathway for long chain fatty acids. Equivalent enzymes for shorter chain fatty acids are soluble proteins of the mitochondrial matrix.
Summary of one round of the b-oxidation pathway:
fatty acyl-CoA + FAD + NAD+ + HS-CoA →
fatty acyl-CoA (2 C shorter) + FADH2 + NADH + H+ + acetyl-CoA
The b-oxidation pathway is cyclic. The product, 2 carbons shorter, is the input to another round of the pathway. If, as is usually the case, the fatty acid contains an even number of C atoms, in the final reaction cycle butyryl-CoA is converted to 2 copies of acetyl-CoA
ATP production:
- FADH2 of Acyl CoA Dehydrogenase is reoxidized by transfer of 2 e- via ETF to coenzyme Q of the respiratory chain. H+ ejection from the mitochondrial matrix that accompanies transfer of 2 e- from CoQ to oxygen, leads via chemiosmotic coupling to production of approximately 1.5 ATP. (Approx. 4 H+ enter the mitochondrial matrix per ATP synthesized.)
- NADH is reoxidized by transfer of 2 e- to the respiratory chain complex I. Transfer of 2 e- from complex I to oxygen yields approximately 2.5 ATP.
- Acetyl-CoA can enter Krebs cycle, where the acetate is oxidized to CO2, yielding additional NADH, FADH2, and ATP.
- Fatty acid oxidation is a major source of cellular ATP
b-Oxidation of very long chain fatty acids also occurs within peroxisomes
FAD is electron acceptor for peroxisomal Acyl-CoA Oxidase, which catalyzes the first oxidative step of the pathway. The resulting FADH2 is reoxidized in the peroxisome producing hydrogen peroxide FADH2 + O2 à FAD + H2O2
The peroxisomal enzyme Catalase degrades H2O2 by the reaction:
2 H2O2 → 2 H2O + O2
These reactions produce no ATP
Once fatty acids are reduced in length within the peroxisomes they may shift to the mitochondria to be catabolized all the way to CO2. Carnitine is also involved in transfer of fatty acids into and out of peroxisomes
- 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.
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.
Cholesterol synthesis:
Hydroxymethylglutaryl-coenzyme A (HMG-CoA) is the precursor for cholesterol synthesis.
HMG-CoA is also an intermediate on the pathway for synthesis of ketone bodies from acetyl-CoA. The enzymes for ketone body production are located in the mitochondrial matrix. HMG-CoA destined for cholesterol synthesis is made by equivalent, but different, enzymes in the cytosol.
HMG-CoA is formed by condensation of acetyl-CoA and acetoacetyl-CoA, catalyzed by HMG-CoA Synthase.
HMG-CoA Reductase, the rate-determining step on the pathway for synthesis of cholesterol.
TRIGLYCEROL
Triacylglycerols (formerly triglycerides) are the esters of glycerol with fatty acids. The fats and oils that are widely distributed in both plants and animals are chemically triacylglycerols.
They are insoluble in water and non-polar in character and commonly known as neutral fats.
Triacylglycerols are the most abundant dietary lipids. They are the form in which we store reduced carbon for energy. Each triacylglycerol has a glycerol backbone to which are esterified 3 fatty acids. Most triacylglycerols are "mixed." The three fatty acids differ in chain length and number of double bonds
Structures of acylglycerols :
Monoacylglycerols, diacylglycerols and triacylglycerols, respectively consisting of one, two and three molecules of fatty acids esterified to
a molecule of glycerol
Lipases hydrolyze triacylglycerols, releasing one fatty acid at a time, producing diacylglycerols, and eventually glycerol
Glycerol arising from hydrolysis of triacylglycerols is converted to the Glycolysis intermediate dihydroxyacetone phosphate, by reactions catalyzed by:
(1) Glycerol Kinase
(2) Glycerol Phosphate Dehydrogenase
Free fatty acids, which in solution have detergent properties, are transported in the blood bound to albumin, a serum protein produced by the liver.
Several proteins have been identified that facilitate transport of long chain fatty acids into cells, including the plasma membrane protein CD36
Biotin
Biotin helps release energy from carbohydrates and aids in the metabolism of fats, proteins and carbohydrates from food.
RDA The Adequate Intake (AI) for Biotin is 30 mcg/day for adult males and females
Biotin Deficiency Biotin deficiency is uncommon under normal circumstances, but symptoms include fatigue, loss of appetite, nausea, vomiting, depression, muscle pains, heart abnormalities and anemia.