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Reduction in alpha chain synthesis is called alpha thalassemia medications bad for your liver discount 250 mg meldonium visa, while deficient beta chain synthesis is the beta thalassemia treatment kidney stones 250 mg meldonium fast delivery. Inheritance Beta thalassemias are phenotypically described as beta (+) or beta (o) depending on whether there is beta chain synthesis or not medications depression cheap 250 mg meldonium with amex. Since there are 2 pairs of alpha genes per cell medicine rising appalachia lyrics discount meldonium 500mg with visa, a single gene deletion in one chromosome or a pair of genes in the chromosomes does not have much effect on a chain production. Alpha thalassemia is rarer because alpha chain deficiency is incompatible with life. These syndromes are mainly seen in people of Asian, African and Mediterranean origin. In homozygous state, clinical manifestations are severe, and hence called Thalassemia major. In heterozygous conditions, the clinical signs and symptoms are minimal; they are called Thalassemia minor. Defect in heme synthesis: Nutritional deficiency of iron, copper, pyridoxal phosphate, folic acid, vitamin B12 or vitamin C. Defect in regulators: Erythropoietin synthesis is reduced in chronic renal failure. Hemorrhage Hematuria, hematemesis, hemoptysis, peptic ulcer metrorrhagia and hemorrhoides are the usual causes for hemorrhage. These precipitates or inclusion bodies lead to membrane damage and destruction of red cells. Homozygous beta thalassemia is characterized by severe anemia, hypersplenism and. The marrow in the skull bones expand producing the "hair-on-end appearance" described in X-ray. Hemoglobin Lepore It is composed of 2 alpha chains and 2 delta-beta chimeric chains. The Hb carries oxygen from lungs to tissue capillaries, from where oxygen diffuses into tissues. In severe physical exercise, pO2 in muscles lowers to 5 mm Hg, when myoglobin releases all the bound oxygen. Myoglobin in Urine and Blood Severe crush injury causes release of myoglobin from the damaged muscles. Being a small molecular weight protein, Mb is excreted through urine (myoglobinuria). Serum myoglobin estimation is useful in early detection of myocardial infarction (Chapter 23). Perhaps about 75% of patients attending a primary health center may have signs and symptoms directly or indirectly related to anemia. The most common cause for anemia in India, is iron deficiency which is described in Chapter 35. Enzymes used as therapeutic agents Clinical Enzymology and Biomarkers biomarkers are used to detect cardiac diseases, which may be a. Commonly used biomarkers for early detection of acute myocardial infarction are: 1. Markers for Cardiac Diseases Serial testing of the following cardiac enzymes is usually done to guide the prognosis (Box 23. On the other hand, there are a few nonfunctional enzymes in plasma, which are coming out from cells of various tissues due to normal wear and tear. Their normal levels in blood are very low; but are drastically increased during cell death (necrosis) or disease. The reference ranges for enzymes in plasma depends on the method of assay used; and therefore will vary from laboratory to laboratory. Hence, the values given in this book are only for a general guidance, and should not be taken as absolute. Cardiac Biomarkers A biomarker is a clinical laboratory test which is useful in detecting dysfunction of an organ. The area under the peak and slope of initial rise are proportional to the size of infarct. However, Troponins are now accepted as reliable markers for myocardial infarction, and hence discussed here. Troponin I (TnI) is encoded by 3 different genes, giving rise to 3 isoforms; the "slow" and "fast" moving forms are skeletal variety.

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Trans fatty acids adversely affect multiple risk factors medications bipolar cheap meldonium 250mg otc, including plasma lipids and lipoproteins symptoms 6 months pregnant purchase meldonium on line amex, systemic inflammation medicine in ancient egypt order meldonium 500 mg without a prescription, endothelial dysfunction medications dictionary purchase meldonium discount, insulin resistance, diabetes and adiposity. It is high in processed foods and bakery products, where partially hydrogenated vegetable oils are used for cooking. Properties of Fatty Acids the composition of some of the common oils and fats are given in Table 7. For example, stearic acid (C18 fatty acid, no double bond) has the melting point 69oC, oleic acid (C18, 1 double bond) has 13oC; linoleic acid (C18, 2 double bonds) has ­5oC and linolenic (C18, 3 double bonds) has ­10oC. Ester Formation Both saturated and unsaturated fatty acids form esters with alcohols, especially with glycerol. Glycerol + fatty acid Mono acyl glycerol Monoglyceride + fatty acid Di acyl glycerol Diglyceride + fatty acid Triglyceride or tri acyl glycerol 6. Oxidation of Fatty Acids All fatty acids undergo oxidation in the body to give energy. However, the unsaturated fatty acids can undergo auto oxidation, due to the presence of the highly reactive double bonds and a variety of products. But the old terminology of monoglyceride, diglyceride and triglyceride are still popular, especially among clinical laboratory workers. If all the three hydroxyl groups of the glycerol are esterified to the same fatty acid, a simple triacyl glycerol is formed. A mixed triglyceride is formed, when different fatty acids are esterified to the hydroxyl groups of glycerol. Generally two hydroxyl groups are esterified to similar fatty acid and the third with a different one. Oils are liquids at 20oC; they are triglycerides which contain a higher proportion of unsaturated fatty acids or short chain triglycerides. Fats are solids at room temperature and contain mainly saturated long chain fatty acids. Fats containing medium chain triglycerides or unsaturated fatty acids are soft fats. Storage of Energy as Fat the triacylglycerols are the storage form of lipids in the adipose tissue. If the same calories were stored as hydrated glycogen, the total weight of this alone would have been 65 kg. Triglycerides in the body are hydrolysed by enzymes, lipases which are hydrolases (class 3 enzymes, Chapter 5). Triacyl glycerol is sequentially hydrolysed to diacyl glycerol and mono acyl glycerol and finally glycerol plus 3 fatty acids. When triglycerides are hydrolysed by alkali, the process is known as saponification. Saponification number is defined as the number of milligrams of potassium hydroxide required to saponify one gram of fat. It is an indication of the molecular weight of the fat, and is inversely proportional to it. Human fat has a saponification number of 194-198, butter has 210-230 and coconut oil has 253-262. Iodine Number Iodine number of a fat is defined as the number of grams of iodine taken up by 100 grams of fat. It is an index of the degree of unsaturation and is directly proportional to the content of unsaturated fatty acids. The term rancidity refers to the appearance of an unpleasant smell and taste for fats and oils. Hydrolytic rancidity is due to partial hydrolysis of the triacyl glycerol molecules due to traces of hydrolytic enzymes present in naturally occurring fats and oils. Oxidative rancidity is the result of partial oxidation of unsaturated fatty acids with resultant formation of epoxides and peroxides of small molecular weight fatty acids by peroxides and free radicals. The same process, if it occurs in vivo will affect the integrity of biomembranes, leading to cell death. Repeated heating of oils would lead to the formation and polymerisation of cyclic hydrocarbons. Coconut oil having medium chain saturated fatty acids will withstand such polymerisation.

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Reduction of sugar to alcohol 66 Textbook of Biochemistry; Section A: Chemical Basis of Life Table 6 stroke treatment 60 minutes purchase meldonium us. Glycosides Sugar + Glucose Aglycon = Glycoside phloretin Phlorhizin Source Importance Rose bark Renal damage Leaves of foxglove Leaves of indigofera Cardiac stimulant Stain Galactose symptoms for diabetes buy meldonium 500mg overnight delivery, digitogenin Digitonin xylose Glucose indoxyl Plant indican symptoms influenza purchase meldonium 250mg mastercard. When the hemi-acetal group (hydroxyl group of the anomeric carbon) of a monosaccharide is condensed with an alcohol or phenol group medicine cabinets order meldonium 500mg on-line, it is called a glycoside. They may be hydrolysed by boiling with dilute acid, so that sugar is free and can then reduce copper. Alpha-glycosides are hydrolysed by maltase from yeast, while beta-glycosides are hydrolysed by Emulsin from almonds. Formation of Esters Hydroxyl groups of sugars can be esterified to form acetates, propionates, benzoates, phosphates, etc. Glucose-6-phosphate and glucose-1-phosphate are important intermediaries of glucose metabolism. Amino groups may be substituted for hydroxyl groups of sugars to give rise to amino sugars. The amino group in the sugar may be further acetylated to produce N-acetylated sugars such as N-acetyl-glucosamine (GluNac). This is because the linkage involves first carbon of glucose and second carbon of fructose, and free reducing groups are not available. A sugar solution which is originally nonreducing, but becomes reducing after hydrolysis, is identified as sucrose (specific sucrose test). Test is negative for sucrose; but when sucrose is hydrolysed, the test becomes positive (specific sucrose test) 68 Textbook of Biochemistry; Section A: Chemical Basis of Life. Therefore the products will change the dextrorotation to levorotation, or the plane of rotation is inverted. The anomeric carbon atom of beta-galactose is attached to the 4th hydroxyl group of glucose through beta-1,4 glycosidic linkage. The lactose may be alpha or beta variety, depending on the configuration of 1st carbon of glucose moiety. Lactose forms osazone which resembles "badminton ball" or "hedgehog" or flower of "touch-me-not" plant. Maltose may be alpha or beta depending on the configuration at the free anomeric carbon atom. Thus first carbon of one glucose residue is attached to the sixth carbon of another glucose through a glycosidic linkage. The enzyme oligo1,6-glucosidase present in intestinal juice can hydrolyse isomaltose into glucose units. Lactose and Lactate are Different Lactose is the milk sugar; a disaccharide made of galactose and glucose. Salient Features of Important Sugars Monosaccharides Glucose aldohexose Galactose 4th epimer of glucose Mannose 2nd epimer of glucose Fructose Ketohexose Disaccharides Glucose + Galactose = Lactose (reducing) Glucose + Glucose = Maltose (reducing) Glucose + Fructose = Sucrose (nonreducing) 69 the salient features of important sugars are shown in Box 6. When starch is treated with boiling water, 10-20% is solubilized; this part is called amylose. The insoluble part absorbs water and forms paste like gel; this is called amylopectin. Amylopectin is also made up of glucose units, but is highly branched with molecular weight more than 1 million. Starch will form a blue colored complex with iodine; this color disappears on heating and reappears when cooled. When starch is hydrolysed by mild acid, smaller and smaller fragments are produced. Thus hydrolysis for a short time produces amylodextrin which gives violet color with iodine and is nonreducing. Later achrodextrins (no color with iodine, but reducing) and further on, maltose (no color with iodine, but powerfully reducing) are formed on continued hydrolysis. Salivary amylase and pancreatic amylase are alpha-amylases, which act at random on alpha1,4 glycosidic bonds to split starch into smaller units (dextrins), and finally to alpha-maltose. Beta-amylases are of plant origin (almond, germinating seeds, etc) which split starch to form beta-maltose. When beta-amylase acts on amylopectin, maltose units are liberated from the ends of the branches of amylopectin, until the action of enzyme is blocked at the 1,6-glycosidic linkage.

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Substrate Inhibition Inhibition of an enzyme by its substrate occurs whenever a dead-end enzyme-substrate complex forms medications dispensed in original container buy meldonium 500mg with mastercard. Such a reaction usually occurs at high substrate concentrations and is due to that substrate binding to a form of enzyme with which the product of the substrate normally combines symptoms of pregnancy buy generic meldonium on-line. Two common kinetic mechanisms for substrate inhibition are illustrated in Figure 1 medications like adderall buy meldonium 500mg on-line. The substrate inhibition by B with respect to A would be uncompetitive inhibition treatment plantar fasciitis discount meldonium 500 mg. The two most common mechanisms of substrate inhibition: (a) Uncompetitive inhibition by substrate B with respect to the variable substrate A for an ordered Bi-Bi kinetic mechanism; (b) Competitive inhibition by substrate B with respect to the variable substrate A for a Ping-Pong kinetic mechanism. Ping-Pong mechanisms are subject to substrate inhibition because of the structural similarity of the free enzyme (E) and the covalently modified enzyme (F). Since B, as an inhibitor, and A, as a varied substrate, combine with the same form of enzyme, the inhibition by B would be linear competitive with respect to A (see Competitive Inhibition). When such inhibition occurs, the doublereciprocal Lineweaver-Burk plot looks quite complex. At high concentrations of the variable substrate, there is upward curvature of the plot, and the slope of the line increases as the concentration of the other, fixed substrate moves into the inhibitory range (see below). This equation indicates that the reaction velocity would increase initially with the concentration of A and then decrease with further increases in substrate concentration. Equation 1 can be rearranged in reciprocal form as equation 2: (2) It should be noted that A appears in the denominator of the equation as a substrate and in the numerator as an inhibitor. The result is that an upward curvature is observed in double-reciprocal plots at higher concentrations of substrate. Over the high range of substrate concentrations, equation 2 reduces to equation 3: (3) A plot of data from the curved portion of Figure 2b would yield a straight line that intersects the abscissa at the point where ­A = Ki. Kinetic plots for substrate inhibition: (a) variation of initial velocity as a function of substrate concentration, and (b) double-reciprocal plot of the variation of initial velocity with substrate concentration. Subtilisin Subtilisin is a member of the subtilase family of serine proteinases, of which more than 50 have been identified (1). The name subtilisin was originally given to an enzyme isolated from a culture of Bacillus subtilis. In an attempt to avoid confusion, an alternative nomenclature has been introduced. The Enzyme Commission of the International Union of Biochemistry and Molecular Biology has assigned them to subsection E. It should be noted that some suppliers refer to subtilisins as bacterial proteinases. Other members of the family have been given quite different trivial names such as thermitase and proteinase K. Only the polypeptide chain is depicted as a ribbon, with arrows for b-strands and coils for a-helices. The active site of each subtilisin contains a catalytic triad typical of serine proteinases, and the catalytic mechanism similarly involves an acylenzyme intermediate. These enzymes have broad substrate specificity, although there is some preference for cleavage adjacent to neutral and acidic amino acid residues. They can bring about extensive degradation of denatured proteins and can even degrade some native proteins. This ability to act on native proteins has been used to advantage to explore structure­function relationships of various proteins (3). Stock solutions prepared in glycerol are stable for many months in the frozen state. An enormous number of mutants have been prepared in efforts to alter virtually all aspects of the activity and stability of the enzyme (4). Subtractive Hybridization Subtractive hybridization is a technique for identifying and characterizing differences between two populations of nucleic acids. Subtractive hybridization techniques have identified many differentially expressed sequences from a wide variety of organisms.

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