Small intestine amino acid metabolism

FIGURE 29-2. Levodopa absorption and metabolism. Levodopa is absorbed in the small intestine and is distributed into the plasma and brain compartments by an active transport mechanism. Levodopa is metabolized by dopa decarboxylase, monoamine oxidase, and catechol-O-methyltransferase. Carbidopa does not cross the blood-brain barrier. Large, neutral amino acids in food compete with levodopa for intestinal absorption (transport across gut endothelium to plasma). They also compete for transport across the brain (plasma compartment to brain compartment). Food and anticholinergics delay gastric emptying resulting in levodopa degradation in the stomach and a decreased amount of levodopa absorbed. If the interaction becomes a problem, administer levodopa 30 minutes before or 60 minutes after meals. 

Liver, small intestine, muscle and kidney all participate in amino acid catabolism with the liver, under most conditions, playing the major role, but the metabolism of specific amino acids in the other three tissues is of considerable biochemical and physiological importance (see below). 

At least five amino acids - glutamine, glutamate, aspartate, asparagine and arginine - are metabolised largely within the enterocytes of the small intestine. The reactions involved in their metabolism are ... 

Between them, the bone marrow and the small intestine possess the highest number of proliferating cells in the body. The bone marrow contains stem cells which proliferate and differentiate to produce red and white blood cells (Chapter 17). This requires not only this amino acids to support protein synthesis but also glutamine, both as a fuel and as a precursor for nucleotides, as in the other proliferating cells. The pathway for metabolism of glutamine in cells isolated from the bone marrow is similar to that in lymphocytes (Figure 8.28). 

Digestion of proteins occurs by enzymatic hydrolysis in the small intestine (Figure 4.3). The digestion of protein produces single amino acids. These can enter the bloodstream through the small intestine walls. The amino acids circulate in the bloodstream until further metabolized or used for protein synthesis there is not a storage depot for amino acids as there is for lipids, which are stored in fat depots in adipose tissue. However, the body does break down protein tissue (muscle) to provide amino acids in the bloodstream. 

Metabolic Transit. Free Amadori Compounds. It is well known that the synthetic Amadori compounds of the free amino acids are absorbed by the intestine and excreted unchanged in the urine (9,28,30). The transport is not active as observed with deoxyfructosyltryptophan (30) and c-deoxyfructosyllysine (40), and the level of absorption depends on the nature of the amino acid and on the conditions of ingestion. Nutritional assays and metabolic transit studies performed with radioactive Amadori compounds of tryptophan (12,30), leucine (12), and lysine (9,28,41) given orally or intravenously on normal or anti-biotics-treated animals have shown that the intestinal microflora can regenerate part of the amino acid. This can be absorbed subsequently at a very low level by the caecum or the large intestine and incorporated into the tissue proteins or utilized by the intestinal microflora. Barbiroli (13) showed also that some intestinal enzymes were able to liberate some amino acids from their Amadori compounds but to a very small... 

Absorption and metabolism The drug is absorbed rapidly from the small intestine (when empty of food). Levodopa has an extremely short half-life (1 to 2 hours), which causes fluctuations in plasma concentration. This may produce fluctuations in motor response ( on-off phenomenon), which may cause the patient to suddenly lose normal mobility and experience tremors, cramps, and immobility. Ingestion of meals, particularly if high in protein content, interferes with the transport of levodopa into the CNS. Large, neutral amino acids (for example, leucine and isoleucine) compete with levodopa for absorption from the gut and for transport across the blood-brain barrier. Thus levodopa should be taken on an empty stomach, typically 45 minutes before a meal. Withdrawal from the drug must be gradual. 

There are four major bile acids (see Figures 47-5 to 47-7). Cholic acid and chenodeoxycholic acid, the primary bile acids, are synthesized in the liver. Bacteria metabolize these primary bile acids to the secondary bile acids—deoxy-cholic acid and lithocholic acid, respectively. Bile acids are conjugated in the liver with the amino acids glycine or taurine. This decreases passive absorption in the biliary tree and proximal small intestine, but permits conservation through active transport in the terminal ileum. This combi-... 

The mucosa of the small intestine metabolizes dietary glutamine, glutamate, asparagine, and aspartate by oxidation to CO2 and H2O, or by conversion to lactate, alanine, citrulline, and NH3. These intermediates and the unmetabolized dietary amino acids are transferred to the portal blood and then to the liver for further metabolism. 

Tryptophan appears to be converted to a larger number of metabolites than any of the other amino acids. The degradation of tryptophan in animals occurs mainly in two pathways, I and II (Figure 4.1). The first major pathway (I), initiated by the action of tryptophan dioxygenase, involves oxidation of tryptophan to N - fc > r my I ky n urenine and the formation of a series of intermediates and byproducts, most of which appear in varying amounts in the urine, the sum of which accounts for the total metabolism of tryptophan, approximately. The second pathway (II) involves hydroxylation of tryptophan to 5-hydroxytryptophan and decarboxylation of this compound to 5-hydroxytryptamine (serotonin), a potent vasoconstrictor found particularly in the brain, intestinal tissues, blood platelets, and mast cells. A small percentage (3%) of dietary tryptophan is metabolized via the pathway (III) to indoleacetic acid. Other minor pathways also exist in animal tissues. 

The early postprandial state is illustrated in Figure 16.4. As described, sugars and amino acids are absorbed and transported by the portal blood to the liver. The portal blood also contains a high level of lactate that is a product of enterocyte metabolism. Most lipid molecules are transported from the small intestine in lymph as... 

After orally ingested, L-theanine is absorbed into the blood circulation through the small intestinal tract s brush-border membrane and then distributed to tissues." " It is easily transported into the brain through the blood-brain barrier s leucine-preferring amino acid transporter system L-Theanine does not appear to accumulate. The metabolic fate of theanine after its oral administration was verified to be enzymatically hydrolyzed to glutamic acid and ethylamine in the blood, kidney, liver, and brain then most of the ethylamine generated was immediately excreted into urine, with only a part circulated in plasma. It is completely absent 24 h after administration. 

In the organism that Is required In small amounts In food to sustain the normal metabolic functions of life. The key to this definition Is that this chemical compound must be supplied to the organism because the animal cannot synthesize vitamins. Lack of It produces a specific deficiency syndrome and supplying It cures that deficiency. An exception to this definition Is vitamin D, which can be made In the skin upon adequate exposure to sunlight. However, without adequate exposure, the animal Is dependent on a dietary source. Biotin, panthothenlc acid, and vitamin R are made by bacteria In the human Intestine, based on a symbiotic relation-ship and, thus, are not required by the human. Niacin can also be synthesized In humans from the amino acid tryptophane. 

Figure 9.1 shows an overview of protein metabolism in addition to the dietary intake of about 80 g of protein, almost the same amount of endogenous protein is secreted into the intestinal lumen. There is a small faecal loss equivalent to about 10 g of protein per day the remainder is hydrolysed to free amino acids and small peptides, and absorbed (section 4.4.3). The faecal loss of nitrogen is partly composed of undigested dietary protein, but the main contributors are intestinal bacteria and shed mucosal cells, which are only partially broken down, and the protective mucus secreted by intestinal mucosal goblet cells (see Figure 4.2). Mucus is especially resistant to enzymic hydrolysis, and contributes a considerable proportion of inevitable losses of nitrogen, even on a protein-free diet.

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