Liver cells amino acid metabolism

The physiological relevance together with chnical importance of transamination and deamination is wide-ranging. As an aid to understanding the somewhat complex nature of amino acid metabolism, it can be considered (or imagined) as a metabolic box (represented in Figure 8.13). Some pathways feed oxoacids into the box whereas others remove oxoacids and the ammonia that is released is removed to form urea. The box illustrates the role of transdeamination as central to a considerable amount of the overall metabolism in the liver cell (i.e. protein, carbohydrate and fat metabohsm, see below). 

Amino acid metabolism is important in all tissues/organs but especially so in the liver, intestine, skeletal muscle, adipose tissue, kidney, lung, brain, cells in the bone marrow and cells of the immune system. 

D-Amino acid oxidase D-Amino acids (see p. 5) are found in plants and in the cell walls of microorganisms, but are not used in the synthesis of mammalian proteins. D-Amino acids are, hew ever, present in the diet, and are efficiently metabolized by 1he liver. D-Amino acid oxidase is an FAD-dependent enzyme that catalyzes the oxidative deamination of these amino acid isomers. The resulting a-ketoacids can enter the general pathways of amino acid metabolism, and be reaminated to L-isomers, or cafe balized for energy. 

The concentrations of individual amino acids in physiological fluids reflect a balance between (1) intestinal uptake, (2) anabolic use by the liver, (3) the synthesis and turnover of the body s structural proteins, and (4) integrity of renal functions (filtration and tubular reabsorption). Any interference or unusual event in the metabolism, growth, or replication of the body s cells and tissues that affects protein and amino acid metabolism could be accompanied by either accumulation or excessive losses of one or more amino acids. 

Processes occurring inside the mitochondrial matrix include pyruvate oxidation, fatty acid oxidation, amino acid metabolism, and the citric acid cycle. Furthermore, respiratory proteins are bound to the inner membrane, so the density of cristae corresponds to the respiratory activity of a cell. For example, mitochondria in heart muscle cells (high rates of respiration) are densely packed with cristae, whereas mitochondria in liver cells (low rates of respiration) have more sparsely distributed cristae. 

In animals, cobalt only occurs as a component of vitamin B-12 (properly called cyanoco-balamin). All animals use vitamin B-12 in amino acid metabolism and red blood cell formation, and ruminants especially use it for converting rumen fermentation products into glucose in the liver. But again, plants do not have red blood cells, rumens, or livers, and thus have no need for either vitamin B-12 or any other molecules that contain cobalt. 

Plisetskaya EM, Bhattachacharya S, Dickoff WW, Gorbman A (1984) The effect of insulin on amino acid metabolism and glycogen content in isolated liver cells of juvenile coho salmon (Oncorhynchus kisutchi). Comp Biochem Physiol 78A 773-778... 

Figure 15-7. Intracellular location and overview of major metabolic pathways in a liver parenchymal cell. (AA —metabolism of one or more essential amino acids AA <->, metabolism of one or more nonessential amino acids.)...

Insulin also plays a role in fat metabolism. In humans, most fatty acid synthesis takes place in the liver. The mechanism of action of insulin involves directing excess nutrient molecules toward metabolic pathways leading to fat synthesis. These fatty acids are then transported to storage sites, predominantly adipose tissue. Finally, insulin stimulates the uptake of amino acids into cells where they are incorporated into proteins. 

A much more serious genetic disease, first described by Foiling in 1934, is phenylketonuria. Here the disturbance in phenylalanine metabolism is due to an autosomal recessive deficiency in liver phenylalanine hydroxylase (Jervis, 1954) which normally converts significant amounts of phenylalanine to tyrosine. Phenylalanine can therefore only be metabolized to phenylpyruvate and other derivatives, a route which is inadequate to dispose of all the phenylalanine in the diet. The amino acid and phenylpyruvate therefore accummulate. The condition is characterized by serious mental retardation, for reasons which are unknown. By the early 1950s it was found that if the condition is diagnosed at birth and amounts of phenylalanine in the diet immediately and permamently reduced, mental retardation can be minimized. The defect is shown only in liver and is not detectable in amniotic fluid cells nor in fibroblasts. A very sensitive bacterial assay has therefore been developed for routine screening of phenylalanine levels in body fluids in newborn babies. 

Muscle protein catabolism generates amino acids some of which may be oxidized within the muscle. Alanine released from muscle protein or which has been synthesized from pyruvate via transamination, passes into the blood stream and is delivered to the liver. Transamination in the liver converts alanine back into pyruvate which is in turn used to synthesise glucose the glucose is exported to tissues via the blood. This is the glucose-alanine cycle (Figure 7.11). In effect, muscle protein is sacrificed in order to maintain blood adequate glucose concentrations to sustain metabolism of red cells and the central nervous system. 

The calorific capacity of amino acids is comparable to that of carbohydrates so despite their prime importance in maintaining structural integrity of cells as proteins, amino acids may be used as fuels especially during times when carbohydrate metabolism is compromised, for example, starvation or prolonged vigorous exercise. Muscle and liver are particularly important in the metabolism of amino acids as both have transaminase enzymes (see Figures 6.2 and 6.3 and Section 6.4.2) which convert the carbon skeletons of several different amino acids into intermediates of glycolysis (e.g. pyruvate) or the TCA cycle (e.g. oxaloacetate). Not all amino acids are catabolized to the same extent... 

Mechanism of Action Anantitubercularthat inhibits cell wall synthesis by competing with the amino acid, o-alanine, for incorporation into the bacterial cell wall. Therapeutic Effect Causes disruption of bacf erial cell wall. Bactericidal or bacteriostatic. Pharmacokinetics Readily absorbed from the gastrointestinal (GI) tract. No protein binding. Widely distributed (including cerebrospinal fluid [CSF ). Metabolized in liver. Primarily excreted in urine. Removed by hemodialysis. Half-life 10 hr. 

All human tissues are capable of synthesizing the nonessential amino acids, amino acid remodelling and conversion of non-amino-acid carbon skeletons into amino acids and other derivatives that contain nitrogen. However, the liver is the major site of metabolism of nitrogenous compounds in the body. Dietary proteins are the primary source of essential amino acids (or nitrogen). Digestion of dietary proteins produces amino acids, which are absorbed through epithelial cells and enter the blood. Various cells take up these amino acids that enter the cellular pools. 

The liver is involved in a variety of both synthetic and catabolic functions, including metabolism of amino acids, lipids, carbohydrates, protein synthesis and detoxification [ 1 ]. These metabolic functions are performed mainly by hepatocytes, although the liver is made of three major cell types (hepatocytes, biliary epithelial cells and Kupffer cells). Exerting many different metabolic functions, the liver contains several different and specific enzymes, leakage of which into the bloodstream occurs in hepatic diseases. 

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