Chylomicrons conversion

In the body retinol can also be made from the vitamin precursor carotene. Vegetables like carrots, broccoli, spinach and sweet potatoes are rich sources of carotene. Conversion to retinol can take place in the intestine after which retinyl esters are formed by esterifying retinol to long chain fats. These are then absorbed into chylomicrons. Some of the absorbed vitamin A is transported by chylomicrons to extra-hepatic tissues but most goes to the liver where the vitamin is stored as retinyl palmitate in stellate cells. Vitamin A is released from the liver coupled to the retinol-binding protein in plasma. 

A major pathway by which LDL are catabolized in hepatocytes and other cells involves receptor-mediated endocytosis. Cholesteryl esters from the LDL core are hydrolyzed, yielding free cholesterol for the synthesis of cell membranes. Cells also obtain cholesterol by de novo synthesis via a pathway involving the formation of mevalonic acid by HMG-CoA reductase. Production of this enzyme and of LDL receptors is transcriptionally regulated by the content of cholesterol in the cell. Normally, about 70% of LDL is removed from plasma by hepatocytes. Even more cholesterol is delivered to the liver via remnants of VLDL and chylomicrons. Thus, the liver plays a major role in the cholesterol economy. Unlike other cells, hepatocytes are capable of eliminating cholesterol by secretion of cholesterol in bile and by conversion of cholesterol to bile acids. 

Kinetic studies in normal human subjects show that 70—100% of the apoB of VLDL is converted to LDL apoB, and alll LDL apoB is derived from VLDL (B31, PI, R5, S35). When radiolabeled chylomicrons were reinfused into a subject with failure of apoB-100 production, the plasma half-life of the apoB-48 was 50 minutes, with no conversion to LDL (M20, M21). Studies on subjects with hypertriglyceridemia have suggested that up to two-thirds VLDL-apoB is removed from the circulation as IDL-sized particles and not metabolized to form LDL (F16, R5). However, VLDL may be heterogeneous in several respects. The VLDL fraction of fasted individuals with hypertriglyceridemia may contain both apoB-100 and apoB-48 (K2). VLDL... 

Critical to vitamin D3 action is its further metabolic conversion to more active compounds (Figure 1.3). Via its transport by DBP, vitamin D3 accumulates in the liver [48]. In rats, as much as 60-80% of an injected or oral dose of vitamin D3 locates to the liver [49-51], Intestinal absorption of vitamin D3 is in association with the chylomicron fraction via the lymphatic system. Vitamin D3 is delivered to the liver in blood from the thoracic duct only a few hours post ingestion [44], A specific portion of hepatic vitamin D3 in the rat is converted to 25-OH-D3 by a 25-hydroxylase system in the endoplasmic reticulum of hepatocytes [52, 53]. This enzyme (Km 10"8 M) is regulated to an extent by 25-OH-D3 and its metabolites. Higher concentrations of vitamin D3 are handled by a second 25-hydroxylase located in liver mitochondria [54], This enzyme, also known as CYP27, 27-hydroxylates cholesterol and thus appears less discriminating than the microsomal 25-OHase which does not use cholesterol as substrate [55, 56]. In humans, however,... 

The free fatty acids that enter muscle tissue can undergo immediate oxidation to be used as an energy source. Those that enter adipose tissue undergo immediate conversion back to TGs for storage in the adipocyte. These stored TGs are mobilized eventually for use as an energy source. Some are destined for immediate removal, whereas others may remain stored as TXjs for more than one year The falty acids of chylomicrons also are released into lactating breast tissue. Here, they are converted to TGs and secreted in the form of milk lipoproteins. 

Conversion of VLDLs to VLDL Remnants in the Bloodstream HDLs and the Cycling of Cholesterol Lipids in Lipoproteins Studies on the Behavior of Lipoproteins Appearance of Chylomicrons in the Bloodstream Following a Meal of Fat or Oil... 

Fig. 7. Role of hepatic lipoprotein receptors in lipoprotein metabolism. The central role of hepatic receptors and the importance of apoE in the clearance of chylomicron remnants (remnant receptor), VLDL (LDL receptors), IDL (LDL receptors), and HDL-with apoE (LDL receptors) are indicated. In addition, the suggested role of apoE and hepatic lipase (HL) in the conversion of IDL to LDL is shown.

Fic. 11. Effect of receptor-binding-defective forms of apolipoprotein E on the hepatic clearance of plasma lipoproteins. Defective forms of apoE result in reduced clearance of chylomicron remnants, VLDLs, and IDLs and their accumulation in plasma. The chylomicron remnants and VLDLs are enriched in cholesteryl esters as the result of CETP activity, and together they constitute the /3-VLDLs, which are a hallmark of type 111 hyperlipoproteinemia. A block in the conversion of IDLs to LDLs by hepatic lipase by the presence of an abnormal apoE form also is indicated. 

This disorder is characterized by marked hyperchylomi-cronemia and a corresponding hypertriglyceridemia (triglyceride as high as 10,000 mg/dL). As discussed previously, LPL is essential for the hydrolysis of triglyceride and the conversion of chylomicrons to chylomicron remnants. The massive accumulation of chylomicrons in the circulation indicates the inability to catabolize dietary fat. The concentration of VXDL cholesterol is usually normal and the concentrations of HDL cholesterol and LDL cholesterol are low (type I pattern). Furthermore, the concentration of apo C-II, the activator of LPL, is normal. 

This reaction is responsible for formation of most of the cholesteryl ester in plasma. The preferred substrate is phosphatidylcholine, which contains an unsaturated fatty acid residue on the 2-carbon of the glycerol moiety. HDL and LDL are the major sources of the phosphatidylcholine and cholesterol. Apo A-I, which is a part of HDL, is a powerful activator of LCAT. Apo C-I has also been implicated as an activator of this enzyme however, activation may depend on the nature of the phospholipid substrate. LCAT is synthesized in the liver. The plasma level of LCAT is higher in males than in females. The enzyme converts excess free cholesterol to cholesteryl ester with the simultaneous conversion of lecithin to lysolecithin. The products are subsequently removed from circulation. Thus, LCAT plays a significant role in the removal of cholesterol and lecithin from the circulation, similar to the role of lipoprotein lipase in the removal of triacylglycerol contained in chylomicrons and VLDL. Since LCAT regulates the levels of free cholesterol, cholesteryl esters, and phosphatidylcholine in plasma, it may play an important role in maintaining normal membrane structure and fluidity in peripheral tissue cells. 

A major effect of insulin is on the adipose tissue, both in regard to glucose uptake and intracellular metabolic effects. The major metabolic conversion in response to insulin is a dephosphorylation of hormonesensitive lipase to convert this enzyme into the inactive form. A second important metabolic aspect is an increase in synthesis and secretion to the blood-vessel surface of lipoprotein lipase. This enzyme is responsible for breaking down circulating triacylglycerols, particularly from VLDL as well as from chylomicrons, into fatty acids and glycerol. 

A newly secreted chylomicron particle contains 3 X l(p TG molecules. The catalytic rate of TG hydrolysis by LPL is about 10/s. Even if chylomicron TGs were hydrolyzed simultaneously by several LPL molecules, conversion of a chylomicron to a TG-depleted remnant would take 10-15 min, and for a VLDL would take >30 min. A question that has been raised is does the substrate particle remain bound to LPL at the vascular endothelial surface, or is it released back into the circulation, then rebound and released again. 

Cholesterol in blood plasma is conjugated with other fipid molecules and with carrier proteins. These fipoprotein complexes may form droplets called chylomicrons, but cholesterol is usually transported as part of a number of larger lipoproteins, including low density lipoprotein (LDL), which carries cholesterol from the fiver to muscle and other tissues, and high density fipoprotein (HDL), which carries cholesterol to the fiver for conversion to bile acids. Physicians are especially concerned when patients have high levels of LDL (the so-called bad cholesterol) in blood moderate exercise and... 

The conversion of nascent chylomicrons to mature chylomicrons reqnires which of the following ... 

Fig. 33.24. Conversion of the fatty acid (FA) from the triacylglycerols (TG) of chylomicrons and VLDL to the TG stored in adipose cells. Note that insulin stimulates both the transport of glucose into adipose cells and the secretion of LPL from the cells. Glucose provides the glycerol 3-phosphate for TG synthesis. Insulin also stimulates the synthesis and secretion of lipoprotein lipase (LPL). Apoprotein C-II activates LPL.

The free FA and MAG are absorbed by the enterocytes of the intestinal wall and absorbed Upids are transported in water-soluble form to other tissues. FA with chain lengths shorter than 14 carbon atoms are bound to albumin and preferentially transported directly to the liver via the portal vein. Only a smaU proportion of MCFA undergoes a conversion to LCFA and esterified to TAG. A very small fraction of LCFA is transported via the portal route. This fraction increases when long-chain TAGs are fed in combination with medium-chain TAGs. The absorbed hpid fractions consist of FA, 2-MAG, some 1-MAG, lyso PL, some PL, fat-soluble vitamins, and small amounts of glycerol and cholesterol. The first step in mucosal transport is reesterification, and the second step is the synthesis of transport particles the so-called lipoprotein (chylomicron) and very low-density lipoproteins (VLDL). They enter the bloodstream via the lymph vessels. Lipoprotein hpase located on the interior walls of the capillary blood vessels hydrolyzes the TAG, releasing FA. These enter... 

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