Challenges and Opportunities in Helicopter Industry
The helicopter industry faces infrastructure limitations, regulatory hurdles, and competitive pressures. Yet, with the right strategies, it can drive economic growth by providing essential services and opening up new possibilities. Developing a robust helicopter industry goes beyond luxury; it enables time-sensitive operations, access to remote areas, and transformative impacts on various sectors. Addressing industry fragmentation, skilled workforce availability, and regulatory issues is key to unlocking its full potential.
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BIOMEDICAL IMPORTANCE Cholesterol is present in tissues and in plasma either as free cholesterol or as a storage form, combined with a long-chain fatty acid as cholesteryl ester. In plasma, both forms are transported in lipoproteins . Cholesterol is an amphipathic lipid and as such is : an essential structural component of membranes and of the outer layer of plasma lipoproteins. It is synthesized in many tissues from acetyl-CoA and is the precursor of all other steroids in the body such as corticosteroids, sex hormones, bile acids, and vitamin D. As a typical product of animal metabolism, cholesterol occurs in foods of animal origin such as egg yolk, meat, liver, and brain. Plasma low-density lipoprotein (LDL) is the vehicle of uptake of cholesterol and cholesteryl ester into many tissues. Free cholesterol is removed from tissues by plasma high-density lipoprotein (HDL) and transported to the liver, where it is eliminated from the body either unchanged or after conversion to bile acids in the process known as reverse cholesterol transport. Cholesterol is a major constituent of gallstones. However, its chief role in pathologic processes is as a factor in the genesis of atherosclerosis of vital arteries, causing cerebrovascular, coronary, and peripheral vascular disease
Step 1Biosynthesis of Mevalonate: HMG-CoA since cholesterol synthesis is extramitochondrial, two molecules of acetyl-CoA condense to form acetoacetyl-CoA catalyzed by cytosolic thiolase. Acetoacetyl-CoA condenses with a further molecule of acetyl-CoA catalyzed by HMG-CoA synthase to form HMG-CoA, which is reduced to mevalonate by NADPH catalyzed by HMG-CoA reductase. This is the principal regulatory step in the pathway of cholesterol synthesis and is the site of action of the most effective class of cholesterol-lowering drugs, the HMG-CoA reductase inhibitors (statins) . Step 2 Formation of Isoprenoid Units: Mevalonate is phosphorylated sequentially by ATP by three kinases, and after decarboxylation the active isoprenoid unit, isopentenyl diphosphate, is formed.
Step 3Six Isoprenoid Units Form Squalene: Isopentenyl diphosphate is isomerized by a shift of the double bond to form dimethylallyl diphosphate, then condensed with another molecule of isopentenyl diphosphate to form the ten-carbon intermediate geranyl diphosphate . A further condensation with isopentenyl diphosphate forms farnesyl diphosphate. Two molecules of farnesyl diphosphate condense at the diphosphate end to form squalene. Initially, inorganic pyrophosphate is eliminated, forming presqualene diphosphate, which is then reduced by NADPH with elimination of a further inorganic pyrophosphate molecule. Step 4 Formation of Lanosterol: Squalene can fold into a structure that closely resembles the steroid nucleus .
CHOLESTEROL SYNTHESIS IS CONTROLLED BY REGULATION OF HMG-CoA REDUCTASE Regulation of cholesterol synthesis is exerted near the beginning of the pathway, at the HMG-CoA reductase step. The reduced synthesis of cholesterol in starving animals is accompanied by a decrease in the activity of the enzyme. However, it is only hepatic synthesis that is inhibited by dietary cholesterol. HMG-CoA reductase in liver is inhibited by mevalonate, the immediate product of the pathway, and by cholesterol, the main product. Cholesterol (or a metabolite, eg, oxygenated sterol) represses transcription of the HMG-CoA reductase gene and is also believed to influence translation. Insulin or thyroid hormone increases HMG-CoA reductase activity, whereas glucagon or glucocorticoids decrease it. Activity is reversibly modified by phosphorylation-dephosphorylation mechanisms, some of which may be cAMP-dependent
The LDL Receptor Is Highly Regulated LDL (apo B-100, E) receptors occur on the cell surfaceAfter binding, LDL is taken up intact by endocytosis. The apoprotein and cholesteryl ester are then hydrolyzed in the lysosomes, and cholesterol is translocated into the cell. The receptors are recycled to the cell surface. This influx of cholesterol inhibits in a coordinated manner HMG-CoA synthase, HMG-CoA reductase,
CHOLESTEROL IS TRANSPORTED BETWEEN TISSUES IN PLASMA LIPOPROTEINS In Western countries, the total plasma cholesterol in humans is about 5.2 mmol/L, rising with age, though there are wide variations between individuals. The greater part is found in the esterified form. It is transported in lipoproteins of the plasma, and the highest proportion of cholesterol is found in the LDL. Dietary cholesterol equilibrates with plasma cholesterol in days
and with tissue cholesterol in weeks. Cholesteryl ester in the diet is hydrolyzed to cholesterol, which is then absorbed by the intestine together with dietary unesterified cholesterol and other lipids. With cholesterol synthesized in the intestines, it is then incorporated into chylomicrons. Of the cholesterol absorbed, 80 90% is esterified with long-chain fatty acids in the intestinal mucosa. Ninety-five percent of the chylomicron cholesterol is delivered to the liver in chylomicron remnants, and most of the cholesterol secreted by the liver in VLDL is retained during the formation of IDL and ultimately LDL, which is taken up by the LDL receptor in liver and extrahepatic tissues
CHOLESTEROL IS EXCRETED FROM THE BODY IN THE BILE AS CHOLESTEROL OR BILE ACIDS (SALTS) About 1 g of cholesterol is eliminated from the body per day. Approximately half is excreted in the feces after conversion to bile acids. The remainder is excreted as cholesterol. Bile Acids Are Formed From Cholesterol The primary bile acids are synthesized in the liver from cholesterol. These are cholic acid (found in the largest amount) and chenodeoxycholic acid
The 7-hydroxylation of cholesterol is the first and principal regulatory step in the biosynthesis of bile acids catalyzed by 7-hydroxylase, a microsomal enzyme. A typical monooxygenase, it requires oxygen, NADPH, and cytochrome P450. Subsequent hydroxylation steps are also catalyzed by monooxygenases. an extra -OH group on position 12, and another pathway leading to chenodeoxycholyl-CoA The primary bile acids enter the bile as glycine or taurine conjugates. Conjugation takes place in peroxisomes. In humans, the ratio of the glycine to the taurine conjugates is normally 3:1. In the alkaline bile,
CLINICAL ASPECTS The Serum Cholesterol Is Correlated With the Incidence of Atherosclerosis & Coronary Heart Disease While cholesterol is believed to be chiefly concerned in the relationship, other serum lipids such as triacylglycerols may also play a role. Atherosclerosis is characterized by the deposition of cholesterol and cholesteryl ester from the plasma lipoproteins into the artery wall. Diseases in which prolonged elevated levels of VLDL, IDL, chylomicron remnants, or LDL occur in the blood (eg, diabetes mellitus, lipid nephrosis, hypothyroidism, and other conditions of hyperlipidemia) are often accompanied by premature or more severe atherosclerosis. There is also an inverse relationship between HDL (HDL2) concentrations and coronary heart disease, and some consider that the most predictive relationship is the LDL:HDL cholesterol ratio. This is consistent with the function of HDL in reverse cholesterol transport
Diet Can Play an Important Role in Reducing Serum Cholesterol Hereditary factors play the greatest role in determining individual serum cholesterol concentrations; however, dietary and environmental factors also play a part, and the most beneficial of these is the substitution in the diet of polyunsaturated and monounsaturated fatty acids for saturated fatty acids. Plant oils such as corn oil and sunflower seed oil contain a high proportion of polyunsaturated fatty acids, while olive oil contains a high concentration of monounsaturated fatty acids. On the other hand, butterfat, beef fat, and palm oil contain a high proportion of saturated fatty acids. Sucrose and fructose have a greater effect in raising blood lipids, particularly triacylglycerols, than do other carbohydrates. The reason for the cholesterol-lowering effect of polyunsaturated fatty acids is still not fully understood. It is clear, however, that one of the mechanisms involved is the up-regulation of LDL receptors by polyand monounsaturated as compared with saturated fatty acids, causing an increase in the catabolic rate of LDL, the main atherogenic lipoprotein. In addition, saturated fatty acids cause the formation of smaller VLDL particles that contain relatively more cholesterol, and they are utilized by extrahepatic tissues at a slower rate than are larger particles tendencies that may be regarded as atherogenic. Lifestyle Affec
