Chylomicrons vitamin absorption

Deficiency of vitamin E is rare it can occur from abnormalities in lipid absorption as well as dietary deficiency. Its deficiency affects the muscular system, causing dystrophy and paralysis and, if the heart is affected, death by myocardial failure. This is probably caused by demyelin-ation of axons due to oxidative damage. Vitamin E is incorporated into chylomicrons within the enterocyte, so that its uptake into cells requires the activity of lipoprotein lipase. 

Vitamin E, like neutral lipids, requires apoB lipoproteins at every stage of its transport (Fig. 27-2). Dietary vitamin E becomes emulsified in micelles produced during the digestive phase of lipid absorption and permeates the intestinal epithelium, similar to fatty acids and cholesterol. Uptake of vitamin E by enterocytes appears to be concentration dependent. Within intestinal cells, vitamin E is packaged into chylomicrons and secreted into lymph. During blood circulation of chylomicrons, some vitamin E may be released to the tissues as a consequence of partial lipolysis of these particles by endothelial cell-anchored lipoprotein lipase. The rest remains associated with chylomicron remnants. Remnant particles are mainly endocy-tosed by the liver and degraded, resulting in the release of fat-soluble vitamins. 

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,... 

Phylloquinone is absorbed in the proximal small intestine, by an energy-dependent mechanism, and is incorporated into chylomicrons. Estrogens increase phylloquinone absorption in both male and female animals, and male animals are more susceptible to dietary vitamin K deprivation than females (loUy et al., 1977). Even after an overnight fast, about half the plasma vitamin K is present in chylomicron remnants, and only a quarter in low-density lipoprotein. The plasma concentration of phylloquinone is associated with genetic variants of apoprotein E, which determines the binding of chylomicron remnants to the liver lipoprotein receptor (Kohlmeier et al., 1996). 

Fat-soluble vitamins require the simultaneous presence of lipids and bile acids for their absorption. In order to be transported to the liver, they are bound to lipoproteins of the chylomicrons. Fat-soluble vitamins are stored in the liver or fatty tissue, often in large amounts and for prolonged periods of time. From there they become available to the intermediary metabolism for complex tasks. Vitamins A and D are secreted from the liver cells by means of carrier proteins. By undergoing biotransformation, fat-soluble vitamins become meta-bolically inactive as well as water-soluble and are thus capable of being excreted, (s. tab. 3.13)... 

Biochemistry. Vitamin D is introduced into the bloodstream either from the skin after natural synthesis by the irradiation of 7-dehydrocholesterol stored in the epidermis (172) or by ingestion and absorption of vitamin D2 or vitamin D through the gut wall (40). Between 60 and 80% of the vitamin introduced in the blood is taken up by the Hver, where cholecalciferol is transferred from chylomicrons to a vitamin D-binding protein (DBF), an OC-globulin specific for vitamin D and its metaboHtes but one which does not bind with previtamin D in the skin (173). Cholecalciferol is hydroxylated in the Hver at the C-25 position (51,141,174). This hydroxylation occurs in the endoplasmic reticulum and requires NADPH, a flavoprotein, cytochrome P-450, Mg ", and O2 (175). 25-Hydroxylation also occurs in intestinal homogenates of chicks (176), but does not appear to occur outside the... 

Vitamin E is absorbed from the gut with the aid of bile salts. The vitamin is not esterified to a fatty acid during absorption, as is the case with cholesterol and retinol. Vitamin E is transported to the bloodstream in chylomicrons and distributed to the various tissues via the lipoproteins. 

Vitamins K and Kj are absorbed by an active process in the proximal small intestines. Bile of normal composition is necessary to facilitate the absorption. The bile component principally concerned in the absorption and transport of fat-soluble vitamin K from the digestive tract is thought to be Jcoxycholic acid. The molecular compound of vitamin K with deoxycholic acid was effective on oral administration to rats with biliary fistula. Vitamin K is absorbed through the lymph in chylomicrons. It is tran.sportcd to the liver, where it is concentrated, but no significant storage occurs. 

The absorption of natural vitamin K from-the small intestine into the lymphatic system is facilitated by bile, as is true for other fat-soluble materials. Efibciency of absorption varies from 15% to 65% as reflected by recovery in lymph within 24 hours. Vitamins Ki and K2 are bound to chylomicrons for transport from mucosal cells to the liver. Menadione (Ks) is more rapidly and completely absorbed from the gut before entering the portal blood. In liver, intraceUular distribution is mostly in the microsomal fraction, where phenylation of menadione to form K2 occurs. Release of vitamin K to the blood stream allows association with circulating P-lipoproteins for transport to other tissue. Significant levels of vitamin K have been noted in the spleen and skeletal muscle. 

The mechanism of intestinal absorption of compounds with vitamin K activity varies with their solubility. In the presence of bile salts, phylloquinone and the menaquinones are adequately absorbed from the intestine, almost entirely by way of the lymph. Phylloquinone is absorbed by an energy-dependent, saturable process in proximal portions of the small intestine menaquinones are absorbed by diffusion in the distal portions of the small intestine and in the colon. Following absorption, phylloquinone is incorporated into chylomicrons in close association with triglycerides and lipoproteins. The extremely low phylloquinone levels in newborns may be partly related to very low plasma lipoprotein concentrations at birth and may lead to an underestimation of vitamin K tissue stores. Absorbed phylloquinone and menaquinones are concentrated in the liver, but the concentration of phylloquinone declines rapidly. Menaquinones, produced in the lower bowel, are less biologically active than phylloquinone due to their long side chain. Very little vitamin K accumulates in other tissues. 

ABSORPTION, FATE, AND EXCRETION Both vitamins and are absorbed from the small intestine and transported as chylomicrons in the lymphatics. Bile salts are essential for adequate absorption. The primary route of vitamin D excretion also is the bile. Severe shortening or inflammation of the small bowel or hepatic or bihary dysfunction may cause overt vitamin D deficiency. 

The rate of vitamin K absorption in humans depends on the kind of fats included in the diet. Long-chain unsaturated fatty acids facilitate absorption of vitamin Kj in lymphatic vessels. The efficiency of this process is affected by the presence of bile salt and pancreatic juices, the form of vitamin K, as well as the site in the gastrointestinal tract. Vitamin Kj is primarily absorbed in the jejunum and ileum only small amounts are absorbed in the colon. From the lymphatic system, vitamin K is transported to the circulatory system and, in chylomicrons, to the liver from which it is distributed to target tissues. 

SD) in order to correspond with the known half-life of chylomicron retinyl esters (IS 10 min) in healthy adult men (Cortner et aL, 1987). Also, the model intestinal absorption of j8-carotene was constrained to be inside the range of two statistical deviations of 15 4.5% based on a j8-carotene balance study (Bowen et aL, 1993) in which 4.3 0.8 punol of a 28-jiunol dose of /3-carotene was absorbed in healthy subjects. Each of these constraints was achieved by including additional data points in the model. Finally, the irreversible loss of retinol from the model system was constrained to a minimum value of 0.7 pimol/day based on the rate of vitamin A depletion in humans (Sauberlich et aL, 1974). These additions to the model provided good statistical certainty on all model parameters, as the FSDs of the FTCs were <25% (see Table I). 

The fat-soluble vitamins A, D, E and K are absorbed by the intestines and incorporated into chylomicrons (Chapter 42). Therefore, diseases that affect fat absorption causing steatorrhoea will also affect the uptake of these vitamins. Furthermore, fat absorption relies on pancreatic lipase, which if compromised, e.g. in cystic fibrosis, can cause deficiency of one or more fat-soluble vitamins. 

Although it has been clearly demonstrated that under normal physiological conditions retinol absorption occurs mainly via the lymphatic route (see above Fidge et al., 1968), the existence of an alternative route for retinol absorption has been suggested both by experimental studies in the rat and by features of the genetic disease abetalipoproteinemia in man. Information available suggests that under abnormal conditions retinol may be able to be absorbed via a nonlymphatic pathway and in a biochemical form other than the chylomicron in amounts sufficient to meet nutritional requirements for vitamin A. 

Vitamin A is transported from the gut to the liver in chylomicrons, and from the Hver to the tissues bound to a specific retinal-binding protein or pre-albumin. Deficiency of vitamin A is usually associated with poor protein diets. It is not necessarily reversible by administration of vitamin A alone since the synthesis of retinolbinding protein is affected by the deficiency and therefore so is vitamin A absorption. Deficiency may cause night blindness, xerophthalmia and keratomalacia. Vitamin A toxicity is unUkely with a normal diet but can cause dermatitis, hair loss, and hepatic dysfunction. In pregnancy it can cause teratogenicity if taken in... 

Figure 3 Absorption of dietary vitamin A (VA) via chylomicrons (CM), vitamin A storage in liver, and the release of retinal to plasma as holo-relinol-binding protein (RBP), which combines with transthyretin (TTR), to deliver retinal to organs that produce retinal (eyes) or retinoic acid (essentially all tissues) for the biological functions attributed to vitamin A.

Intestinal absorption of vitamin E is dependent upon normal processes of fat absorption. Specifically, both biliary and pancreatic secretions are necessary for solubilization of vitamin E in mixed micelles containing bile acids, fatty acids, and monoglycerides (Figure 3). a-Tocopheryl acetates (or other esters) from vitamin E supplements are hydrolyzed by pancreatic esterases to a-tocopherol prior to absorption. Following micellar uptake by entero-cytes, vitamin E is incorporated into chylomicrons and secreted into the lymph. Once in the circulation, chylomicron triglycerides are hydrolyzed by lipoprotein lipase. During chylomicron catabolism in the... 

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