Vitamin liver storage

Once absorbed, vitamin B12 is transported to the various cells of the body bound to a family of specialized glycoproteins, transcobalamin I, II, and III. Excess vitamin B12 is transported to the liver for storage. 

After a tracer dose of radioactive phylloquinone, the label is rapidly accumulated in the liver, then lost from the body with turnover time of 1.5 days. Tbis suggests that there is rapid turnover and little storage of vitamin K. However, there maybe considerable enterohepatic recirculation of the conjugates excreted in the bile (Shearer et al., 1996 Olson et al., 2002). About 10% of the total liver vitamin K is normally present as the epoxide, which is formed by the vitamin K-dependent carboxylase and normally reduced back to tbe active vitamin (Section 5.3.1). 

The retinyl esters are incorporated into chylomicrons, which in turn enter the lymph. Once in the general circula-tion. chylomicrons arc converted into chylomicron remnants, which arc cleared primarily by the liver. As the c.stcrs enter the hepalocytes. they are hydrolyzed. In the endoplasmic reticulum, the retinol is bound to retinol-binding protein (RBP). This cotnplex is released into the blood or transferred to liver stellate cells fur storage. Within the stellate cells, the retinol is bound to CRBP(I) and e.stcnTicd for storage by ARAT and LRAT. Stellate cells contain up to 95% of the liver vitamin A. stores. The RBP-retinol complex released into the general circulation from hepalocytes or stellate cells, in turn, is bound to transthyretin (TTR), which protects retinol from metabolism and renal excretion. ... 

The studies on the tissue concentrations of vitamin A in humans and animals have been limited mainly to determinations of the vitamin A content of the liver. In many vertebrates this organ contains over 90 % of the body storage of the vitamin. After a colorimetric procedure was developed for vitamin A analysis, numerous publications on the liver vitamin A content appeared over the period from 1929 to 1942. It should be pointed out t hat most of the observations on the liver vitamin A values were conducted t>ef()ro the modern chromatographic and photoelectric techniques had luH-oine available and that in rec ent years studies on the liver content of vitamin A have been discontinued to a great extent (Moore, 19r>7). In spite of the fa(it that most of the investigations on the liver vitamin A concentrations were performed with the use of rather primitive analytical methods, the information provided by these earlier studies is nevertheless useful and permits certain conclusions with regard to the correlation between age and liver vitamin A levels. 

The livers of seals have a tendency to a rather high storage of vitamin A. An investigation on the change with age in the liver vitamin A levels of this marine mammal was conducted by Rodahl and Davies (1949). The... 

Vitamin A is assumed to be contained mainly in the Kupffer cells of the liver. The intracellular distribution of the vitamin has also been studied in chicken liver. Twenty-one per cent of the vitamin is found in the nucleus, 7% in the mitochondria, and 72% in the supernatant. Therefore, the vitamin seems to be concentrated essentially in the supernatant fluid, and the amount of vitamin associated with the nucleus and the mitochondria is probably due to contamination of the fraction by the supernatant vitamin A. This intracellular distribution might be peculiar to the liver— the main site of vitamin A storage therefore, the cellular distribution of the vitamin gives no clue as to its mode of action. The liver vitamin is bound to protein. The protein that is bound to the alcohol derivative of vitamin A is probably different from that bound to the ester derivative of vitamin A. 

Vitamin D from skin or dietary sources does not circulate for long in the bloodstream, but instead is immediately taken up by adipose tissue or liver for storage or activation. In humans, tissue storage of vitamin D can last for months or even years. Ultimately, the vitamin D3 undergoes its first step of activation, namely 25-hydroxylation in the liver (Fig. 3). Over the years there has been some controversy over whether 25-hydroxylation is carried out by one enzyme or two and whether this cytochrome P450-based enzyme is found in the mitochondrial or microsomal fractions of liver (25). Currently, only one of these enzymes, the... 

Although there is a significant relationship between plasma retinol and liver vitamin A storage (considered a gold standard for assessing vitamin A status), the relationship is by no means linear. In fact, plasma retinol is nearly constant over a rather wide range of liver vitamin A concentrations, all... 

The first example is the plasma-borne retinol-binding protein, RBP, which is a single polypeptide chain of 182 amino acid residues. This protein is responsible for transporting the lipid alcohol vitamin A (retinol) from its storage site in the liver to the various vitamin-A-dependent tissues. It is a disposable package in the sense that each RBP molecule transports only a single retinol molecule and is then degraded. 

Ascorbic acid is photosensitive and unstable in aqueous solution at room temperature. During storage of foods, vitamin C is inactivated by oxygen. This process is accelerated by heat and the presence of catalysts. Ascorbic acid concentration in human organs is highest in adrenal and pituitary glands, eye lens, liver, spleen, and brain. Potatoes, citrus fruits, blade currants, sea buckthorns, acerola, rose hips, and red paprika peppers are among the most valuable vitamin C sources [1,2]. 

A person with pernicious anemia lacks intrinsic factor, a compound required for the absorption of vitamin B12 and its storage in the liver. The diagnosis is confirmed... 

The sinusoids transport both portal and arterial blood to the hepatocytes. The systemic blood delivered to the liver contains nutrients, drugs, and ingested toxins. The liver processes the nutrients (carbohydrates, proteins, lipids, vitamins, and minerals) for either immediate use or for storage, while the drugs and toxins are metabolized through a variety of processes known as first-pass metabolism. The liver also processes metabolic waste products for excretion. In cirrhosis, bilirubin (from the enzymatic breakdown of heme) can accumulate this causes jaundice (yellowing of the skin), scleral icterus (yellowing of the sclera), and tea-colored urine (urinary bilirubin excretion). 

The liver serves as an important storage site for vitamins and iron. Sufficient quantities of several vitamins may be stored so as to prevent vitamin deficiency for some period of time ... 

In the Artie Eskimos depended historically on fish for their supply of vitamin D, whereas in the tropics a supply is unnecessary. Excessive intakes of vitamins A and D can be lethal. The liver is the storage organ for fat-soluble vitamins Eskimos avoided hypervitaminoses by discarding livers of polar bears which get a surfeit of vitamins A and D from their diet of seals and fish. 

The overall metabolism of vitamin A in the body is regulated by esterases. Dietary retinyl esters are hydrolyzed enzymatically in the intestinal lumen, and free retinol enters the enterocyte, where it is re-esterified. The resulting esters are then packed into chylomicrons delivered via the lymphatic system to the liver, where they are again hydrolyzed and re-esterified for storage. Prior to mobilization from the liver, the retinyl esters are hydrolyzed, and free retinol is complexed with the retinol-binding protein for secretion from the liver [101]. Different esterases are involved in this sequence. Hydrolysis of dietary retinyl esters in the lumen is catalyzed by pancreatic sterol esterase (steryl-ester acylhydrolase, cholesterol esterase, EC 3.1.1.13) [102], A bile salt independent retinyl-palmitate esterase (EC 3.1.1.21) located in the liver cell plasma hydrolyzes retinyl esters delivered to the liver by chylomicrons. Another neutral retinyl ester hydrolase has been found in the nuclear and cytosolic fractions of liver homogenates. This enzyme is stimulated by bile salts and has properties nearly identical to those observed for... 

Vitamin B12 (cyanocobalamin) is produced by bacteria B12 generated in the colon, however, is unavailable for absorption (see below). liver, meat, fish, and milk products are rich sources of the vitamin. The minimal requirement is about 1 pg/d. Enteral absorption of vitamin B 2 requires so-called intrinsic factor from parietal cells of the stomach. The complex formed with this glycoprotein undergoes endocytosis in the ileum. Bound to its transport protein, transcobalamin, vitamin B12 is destined for storage in the liver or uptake into tissues. 

Storage. The liver not only stores energy reserves and nutrients for the body, but also certain mineral substances, trace elements, and vitamins, including iron, retinol, and vitamins A, D, K, folic acid, and Bi2. 

Thus, the accumulation of vitamins respectively micronutrients in single tissues is not limited to a pure storage process like the storage of vitamin A in the liver, but is often connected with important and tissue-specific metabolic functions. 

The main sources of vitamin C are green vegetables and citrus fruit. Animal tissue contains vitamin C, mainly in the kidneys and liver. The level of vitamin C in food is rapidly reduced during cooking or storage due to oxidation or water dissolution. It is added to food as an antioxidant (with no specified limit on the level of use) or as a supplement (with a maximum recommended daily intake of 3000mg/day). The forms admitted are L-ascorbic acid (AA), L-ascorbyl 6-palmitate, sodium, calcium, or potassium L-ascorbate [403]. 

Since vitamin A is a fat-soluble vitamin, any disease that results in fat malabsorption and impaired liver storage brings with it the risk of vitamin A deficiency these conditions include biliary tract disease, pancreatic disease, sprue, and hepatic cirrhosis. One group at great risk are children from low-income families, who are likely to lack fresh vegetables (carotene) and dairy products (vitamin A) in the diet. 

Vitamin D is the collective term for a group of compounds formed by the action of ultraviolet irradiation on sterols. Cholecalciferol (vitamin D3) and calciferol (vitamin D2) are formed by irradiation of the provitamins 7-dehydrocholesterol and ergosterol, respectively. The conversion to vitamin D3 occurs in the skin. The liver is the principal storage site for vitamin D, and it is here that the vitamin is hydroxylated to form 25-hydroxyvitamin D. Additional hydroxylation to form 1,25-dihydroxyvita-min D occurs in the kidney in response to the need for calcium and phosphate. A discussion of the role of vitamin D in calcium homeostasis is provided in Chapter 66. 

L B. Supplement with vitamin A. Vitamin A deficiency symptoms include night blindness that can lead to corneal ulceration. This deficiency can occur in patients with impaired liver storage or fat malabsorption. Dairy products, such as milk, are a good source of vitamin A. (3-Carotene, a vitamin A precursor, is found in pigmented vegetables, such as carrots. When a deficiency is diagnosed, it is appropriate to treat the patient with a supplement rather than to rely on increased consumption of vitamin A-rich foods. A patient with pancreatic disease and malabsorption syndrome will need parenteral supplementation. 

Folic acid deficiency, unlike vitamin B12 deficiency, is often caused by inadequate dietary intake of folates. Patients with alcohol dependence and patients with liver disease can develop folic acid deficiency because of poor diet and diminished hepatic storage of folates. Pregnant women and patients with hemolytic anemia have increased folate requirements and may become folic acid-deficient, especially if their diets are marginal. Evidence implicates maternal folic acid deficiency in the occurrence of fetal neural tube defects, eg, spina bifida. (See Folic Acid Supplementation A Public Health Dilemma.) Patients with malabsorption syndromes also frequently develop folic acid deficiency. Patients who require renal dialysis develop folic acid deficiency because folates are removed from the plasma during the dialysis procedure. 

Altered vitamin A homeostasis, primarily manifested as decreased hepatic storage of vitamin A, is another established effect of PBBs in animals. Vitamin A is essential for normal growth and cell differentiation, particularly differentiation of epithelial cells, and some PBB-induced epithelial lesions resemble those produced by vitamin A deficiency. Because it is the primary storage site for vitamin A, the liver has a major role in retinol metabolism. Esterification of dietary vitamin A, hydrolysis of stored vitamin A, mobilization and release into the blood of vitamin A bound to retinol-binding protein, and much of the synthesis of retinol-binding protein occurs in the liver. 

Formation of 1,25-diOH D3 Vitamins D2 and D3 are not biologically active, but are converted in vivo to the active form of the D vitamin by two sequential hydroxylation reactions (Figure 28.23). The first hydroxylation occurs at the 25-position, and is catalyzed by a specific hydroxylase in the liver. The product of the reaction, 25-hydroxycholecalciferol (25-OH D3), is the predominant form of vitamin D in the plasma and the major storage form of the vitamin. 25-OH D3 is further hydroxylated at the one position by a specific 25-hydroxycholecalciferol 1 -hydroxylase found primarily in the kidney, resulting in the formation of 1,25-dihydroxycholecalciferol j (1,25-diOH D3). [Note This hydroxylase, as well as the iver 25-hydroxylase, employ cytochrome P450, molecular oxygen, and NADPH.]... 

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