Amino acids tubules

Hyperargininemia. This defect is characterized by elevated blood and cerebrospinal fluid arginine levels, low erythrocyte levels of arginase (reaction 5, Figure 29-9), and a urinary amino acid pattern resembling that of lysine-cystinuria. This pattern may reflect competition by arginine with lysine and cystine for reabsorption in the renal tubule. A low-protein diet lowers plasma ammonia levels and abolishes lysine-cystinuria. 

Active reabsorption occurs when the movement of a given substance across the luminal surface or the basolateral surface of the tubular epithelial cell requires energy. Substances that are actively reabsorbed from the tubule include glucose amino acids and Na+, POy3, and Ca++ ions. Three generalizations can be made regarding the tubular reabsorption of sodium, chloride, and water ... 

Na+-glucose, Na+-amino acid, Na+-phosphate, and NaMactate sym-porter mechanisms Na+-H+ antiporter mechanism first half of the proximal tubule... 

Kanai, Y., et al. Expression of mRNA (D2) encoding a protein involved in amino acid transport in S3 proximal tubule. Am. J. Physiol. 1992, 263, F1087-F1092. 

After initial filtration many proteins are actively reabsorbed (endocytosed) by the proximal tubules and subjected to lysosomal degradation, with subsequent amino acid reabsorption. Thus, very little intact protein actually enters the urine. 

The cause is defective transport of dibasic amino acids by the proximal tubule and intestine. The transport defect occurs at the basolateral rather than the luminal membrane. Hyperammonemia reflects a deficiency of intra-mitochondrial ornithine. An effective treatment is oral citrulline supplementation, which corrects the hyperammonemia by allowing replenishment of the mitochondrial pool of ornithine. 

In this chapter, we have surveyed a wide range of chiral molecules that self-assemble into helical structures. The molecules include aldonamides, cere-brosides, amino acid amphiphiles, peptides, phospholipids, gemini surfactants, and biological and synthetic biles. In all of these systems, researchers observe helical ribbons and tubules, often with helical markings. In certain cases, researchers also observe twisted ribbons, which are variations on helical ribbons with Gaussian rather than cylindrical curvature. These structures have a large-scale helicity which manifests the chirality of the constituent molecules. 

In some cases, the amino acid pattern on a paper chromatogram is very similar to that found in diseases of the renal tubules, such as cystinosis, where there is a failure to reabsorb all amino acids from the glomerular filtrate and, in consequence, the urinary amino acid pattern resembles that of plasma (W6, W9). In other cases the aminoaciduria is less marked and the amino acids found in greatest excess are glycine, alanine, serine, threonine, and glutamine. In some cases no aminoaciduria has been detected. 

The LLC-PKi (porcine kidney) cell line (Hull et al., 1976) exhibits a range of morphological and functional properties of proximal tubule epithelium. For example, Na+-dependent glucose and amino acid transport have been demonstrated in LLC-PKi cells (Rabito and Ausiello, 1980 Rabito and Karish, 1982, 1983). LLC-... 

Except for its lower protein concentration, glomerular filtrate at the top of the nephron is chemically identical to the plasma. The chemical composition of the urine is however quantitatively very different to that of plasma, the difference is due to the actions of the tubules. Cells of the proximal convoluted tubule (PCT) are responsible for bulk transfer and reclamation of most of the filtered water, sodium, amino acids and glucose (for example) whereas the distal convoluted tubule (DCT) and the collecting duct are concerned more with fine tuning the composition to suit the needs of the body. 

Proximal tubule Cells of the PCT are responsible for bulk transport of solutes, with approximately 70-80% of the filtered load of sodium chloride (active processes) and water (passive, down the osmotic gradient established by sodium reabsorption) and essentially all of the amino acids, bicarbonate, glucose and potassium being reabsorbed in this region. 

Amino add reabsorption in the renal tubules Amino acids are small, easily filtered molecules. Efficient reabsorption mechanisms are vital to conserve amino acids which are metabolically valuable resources. Transport of individual amino acids and small peptides is symport carrier mediated mechanisms in which sodium is co-transported. The process is indirectly ATP dependent because Na is returned to the lumen of the nephron by the sodium pump , Na+/K+ dependent ATPase. 

Several symport proteins have been identified in the luminal and basolateral surfaces of the proximal tubule cells, each with a specific transport function. For example, mechanisms exist for transport of (i) neutral amino acids, except glycine, (ii) glycine alone, (iii) acidic amino acids (glutamate and aspartate), (iv) basic amino acids... 

The main filtering units of the kidneys are called nephrons-, about one million nephrons are present in each kidney. Each nephron consists of a renal corpuscle and a unit called a tubule. Blood carrying normal metabolic wastes such as urea and creatine moves through a portion of the corpuscle called the glomerulus, where a filtrate forms that contains water, normal metabolic products, and also waste products the filtrate collects in another unit called Bowman s capsule. Glomerular filtrate then moves into a highly convoluted and multifaceted set of tubes - the tubule - where most useful products (water, vitamins, some minerals, glucose, amino acids) are taken back into the blood, and from which waste products are collected as urine. The relative amounts of water and minerals secreted or returned to the blood are under hormonal control. 

Since the intracellular concentration of most amino acids is considerably greater than that in the plasma (Table 8.2), the transport of these amino acids is an energy-requiring process. This is achieved via the Na+ gradient across the plasma membrane, which is maintained by the ATP-dependent Na pump the NaVK+ ATPase (Figure 8.5). This is similar to that of the transport of glucose across the luminal membranes of epithelial cells in the gut and in the tubules is the kidney cortex. 

These strategies are aimed at either cytosolic enzymes, such as L-amino acid decarboxylase, 3-lyase and N-acetyl transferase, or enzymes that are expressed at the brush border of the proximal tubule and to a lesser extent on the basolateral membrane, such as y-glutamyl transpeptidase (GGT). 

The filtered substance is reabsorbed by the tubule. Some important molecules such as glucose and amino acids, and electrolytes such as sodium and chloride ions share this feature. Thus, their concentration in urine underestimates the GFR. 

Animal studies indicate that the primary toxic effect of uranium exposure is on the kidney, with particular damage to the proximal tubules. Functionally, this may result in increased excretion of glucose and amino acids. Structurally the necrosis of tubular epithelium leads to formation of cellular casts in the urine. If exposure is insufficient to cause death from renal failure, the mbular lesion is reversible with epithelial regeneration. Although bone is the other major site of deposition, there is no evidence of toxic or radiocarcinogenic effects to bone or bone marrow from experimental studies. ... 

Hartnup disorder Is a rare condition caused by impaired resorption of neutral amino acids (especially tryptophan, alanine, threonine, glutamine, and histidine) In the renal tubules and malabsorption In the Intestine, resulting from mutations that lead to defective function of a neutral amino acid transporter. 

The answer is D. The patient s symptoms are consistent with a kidney stone, which is confirmed by the radiographic finding. The etiology of the stone is indicated by the urinalysis data, which suggest cystinuria. The cells of this patient s renal proximal tubules would be deficient in a transporter responsible for the reabsorptive uptake of cystine and the basic amino acids, arginine, lysine, and ornithine. Failure of the tubules to reabsorb these amino acids from the ultrafiltrate causes them to be excreted at high concentration in the urine. 

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