Liver nitrogen transport

Alternatively, in skeletal muscle, pyruvate can be transaminated to alanine (which affords a route for nitrogen transport from muscle to liver) in the liver alanine is used to regenerate pyruvate, which can then be diverted into gluconeogenesis. This process is referred to as the glucose-alanine cycle. 

Solubilization and Partial Purification of Cytochrome P-450 from Hepatic Microsomes of Male, DBA-Pretreated Little Skates. Washed hepatic microsomes (3) from the livers of 10 skates were suspended in 0.25 M sucrose and frozen under nitrogen (-5 to -10°) at the Maine laboratory. They were then packed in dry ice and transported to NIEHS, Research Triangle Park, NC, within 14 days of preparation and were stored at -62°C until use. Microsomes... 

Alanine (abbreviated Ala or A) ((S)-2-aminopropanoic acid ct-aminopropionic acid) is a nonpolar, neutral, aliphatic amino acid with the formula HOOCCH(NH2)CH3 Ala plays a major role in the transport of nitrogen from skeletal muscles to the liver. 

Two amino acids—asparagine and glutamine—contain acid-amide groups in the side chains, from which NH3 can be released by hydrolysis (hydrolytic deamination). In the blood, glutamine is the most important transport molecule for amino nitrogen. Hydrolytic deamination of glutamine in the liver also supplies the urea cycle with NH3. 

There is also a corresponding circulation system for the amino acid alanine. The alanine cycle in the liver not only provides alanine as a precursor for gluconeogenesis, but also transports to the liver the amino nitrogen arising in muscles during protein degradation. In the liver, it is incorporated into urea for excretion. 

The skeletal muscle is the most important site for degradation of the branched-chain amino acids (Val, Leu, lie see p. 414), but other amino acids are also broken down in the muscles. Alanine and glutamine are resynthesized from the components and released into the blood. They transport the nitrogen that arises during amino acid breakdown to the liver (alanine cycle see above) and to the kidneys (see p. 328). 

In most terrestrial animals, glutamine in excess of that required for biosynthesis is transported in the blood to the intestine, liver, and kidneys for processing. In these tissues, the amide nitrogen is released as ammonium ion in the mitochondria, where the enzyme glutaminase converts glutamine to glutamate and NHj (Fig. 18-8). The NHj from intestine and kidney is transported in the... 

Cyclophosphamide (Cytoxan, 8.104) is an anticancer prodrug that is oxidized by the C YP2B enzyme family in the liver (Scheme 8.27) and was first introduced back in Chapter 6. Oxidation occurs adjacent to the ring nitrogen to afford 4-hydroxycyclophosphamide (8.105), which is transported throughout the body by the circulatory system. Compound... 

Glucocorticoids also increase the activity of transaminases (aminotransferases), especially in the skeletal muscle. Aminotransferases serve to transfer the amino groups from amino acids to be metabolized to a-keto acids, especially pyruvate. In the latter case, the alanine thus formed is transported from the muscle into the bloodstream and extracted from there by the liver. In the liver, alanine is converted to glucose, and glucose may then return to the muscle as it does in the Cori cycle (Figure 18.4). This is the alanine cycle, and more about this is discussed in Chapter 20. Branched-chain amino acids are the principal donors of nitrogen to pyruvate in the muscle and are thus important actors in the alanine cycle. 

A number of other cytochromes are located in the intermembrane space and the inner surface of the outer mitochondrial membrane. Cyt bs (cytochrome b ) is a small heme protein with a hydrophihc domain of about 95 amino acids and a carboxyl terminus of about 45 hydrophobic amino acids that serve to anchor the protein to the inner surface of the outer mitochondrial membrane. Cyt bs is reduced by NADH-cyt bs reductase, also located on the inner surface of the outer membrane. Under conditions of high intermembrane ionic strength, Cc is released from the inner membrane, and can transport electrons from cyt bs on the outer membrane to CcO on the inner membrane. Cyt bs contains protoheme b with the iron atom hgated by two histidine nitrogen atoms. The heme group has a reduction potential of -1-10 mV versus NHE. Cyt bs is also found on the liver endoplasmic reticulum membrane, where it transfers electrons from NADH-cyt b ... 

Nitrogen is transported from muscle to the liver in two principal transport forms. Glutamate is formed by transamination reactions, but the nitrogen is then transferred to pyruvate to form alanine, which is released into the blood (Figure 23.15). 

The large intestine extends from the ileocecal valve to the anus. It is wider than the small intestine except for the descending colon, which when empty may have the same diameter as the small intestine. Major functions of the colon are absorption of water, Na+, and other electrolytes, as well as temporary storage of excreta followed by their elimination. The colon harbors large numbers of mostly anaerobic bacteria that can cause disease if they invade tissues. These bacteria metabolize carbohydrates to lactate, short-chain fatty acids (acetate, propionate, and butyrate), and gases (CO2, CH4, and H2). Ammonia, a toxic waste product, is produced from urea and other nitrogenous compounds. Other toxic substances are also produced in the colon. Ammonia and amines (aromatic or aliphatic) are absorbed and transported to the liver via the portal blood, where the former is converted to urea (Chapter 17) and the latter is detoxified. The liver thus protects the rest of the body from toxic substances produced in the colon. Colonic bacteria can also be a source of certain vitamins (e.g., vitamin K, Chapter 36). 

In contrast to the case of lipids and carbohydrates, no special storage forms of either the nitrogen or the amino acid components of proteins exist. Dietary protein in excess of the requirement is catabolized to provide energy and ammonia, a toxic metabolite that is converted to urea in the liver and excreted by the kidneys. All body proteins serve a specific function (e.g., structural, catalytic, transport, regulatory) and are potential sources of carbon for energy production. 

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