Protein, amino acid turnover synthesis

The body contains approx. 14,000 g protein in total. There is a 24-hour turnover of 600-700 g of the amino acid pool. The musculature has the highest absolute rate of protein synthesis. The protein synthesized here is retained for exclusive use in the muscles. In relation to its weight, the liver generates more protein than the musculature. The synthesis rate in the liver amounts to 120 g/ day, whereby 70-80% of these proteins are released by the hepatocytes, so that only 20-30% remain available for their own use. Plasma protein turnover is 25 g/day, that of the total tissue protein approx. 150 g/day. Amino acid turnover and protein synthesis proceed rapidly and continuously. 

Fohc acid is a precursor of several important enzyme cofactors required for the synthesis of nucleic acids (qv) and the metaboHsm of certain amino acids. Fohc acid deficiency results in an inabiUty to produce deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and certain proteins (qv). Megaloblastic anemia is a common symptom of folate deficiency owing to rapid red blood cell turnover and the high metaboHc requirement of hematopoietic tissue. One of the clinical signs of acute folate deficiency includes a red and painhil tongue. Vitamin B 2 folate share a common metaboHc pathway, the methionine synthase reaction. Therefore a differential diagnosis is required to measure foHc acid deficiency because both foHc acid and vitamin B 2 deficiency cause... 

There are at least two answers to question (i). First, abnormal proteins can arise in cells due to spontaneous denaturation, errors in protein synthesis, errors in post-translational processing, failure of the correct folding of the protein or damage by free radicals. They are then degraded and replaced by newly synthesised proteins. Secondly, turnover helps to maintain concentrations of free amino acids both within cells and in the blood. This is important to satisfy the requirements for synthesis of essential proteins and peptides (e.g. hormones) and some small nitrogen-containing compounds that play key roles in metabolism (see Table 8.4). 

The biosynthetic incorporation of amino acids into proteins makes these metabolites valuable endogenous tracers for the characterization of protein turnover. Of the naturally occurring amino acids, administration of a bolus dose of pH]leucine is widely used as a tracer in kinetic investigations of protein synthesis and secretion. 

During the normal synthesis and degradation of cellular proteins (protein turnover Chapter 27), some amino acids that are released from protein breakdown and are not needed for new protein synthesis undergo oxidative degradation. 

How the division of spoils came about I do not recall—it may have been by drawing lots. At any rate, David Shemin drew amino acid metabolism, which led to his classical work on heme biosynthesis. David Rittenburg was to continue his interest in protein synthesis and turnover, and lipids were to be my territory. 

To meet these changing circumstances, the liver has remarkable metabolic flexibility. For example, when the diet is rich in protein, hepatocytes supply themselves with high levels of enzymes for amino acid catabolism and gluconeogenesis. Within hours after a shift to a high-carbohydrate diet, the levels of these enzymes begin to drop and the hepatocytes increase their synthesis of enzymes essential to carbohydrate metabolism and fat synthesis. Liver enzymes turn over (are synthesized and degraded) at live to ten times the rate of enzyme turnover in other tissues, such as muscle. Extrahepatic... 

Amino Acids Amino acids that enter the liver follow several important metabolic routes (Fig. 23-14). (1) They are precursors for protein synthesis, a process discussed in Chapter 27. The liver constantly renews its own proteins, which have a relatively high turnover rate (average half-life of only a few days), and is also the site of biosynthesis of most plasma proteins. (2) Alternatively amino acids pass in the bloodstream to other organs, to be used in the synthesis of tissue proteins. (3) Other amino acids are precursors in the biosynthesis of nucleotides, hormones, and other nitrogenous compounds in the liver and other tissues. 

These free amino acids are obtained from the degradation of dietary protein, the constant turnover of body protein, and the synthesis of nonessential amino acids. Free amino acids are consumed by synthesis of body protein and metabolism of their carbon skeletons. 

An initially surprising conclusion drawn from the studies of Schoenheimer and Rittenberg was that proteins within cells are in a continuous steady state of synthesis and degradation. The initial biosynthesis, the processing, oxidative and hydrolytic degradative reactions of peptides, and further catabolism of amino acids all combine to form a series of metabolic loops as discussed in Chapter 17 and dealt with further in Chapters 12 and 29. Within cells some proteins are degraded much more rapidly than others, an important aspect of metabolic control. This is accomplished with the aid of the ubiquitin system (Box 10-C) and proteasomes (Box 7-A).107 Proteins secreted into extracellular fluids often undergo more rapid turnover than do those that remain within cells. 

In chapter 29, Protein Synthesis, Targeting, and Turnover, the processes of protein synthesis and transport are described. First the process whereby amino acids are ordered and polymerized into polypeptide chains is described. Next, posttranslational alterations of newly synthesized polypeptides is considered. This is followed by a discussion of the targeting processes whereby proteins migrate from their site of synthesis to their target sites of function. Finally, proteolytic reactions that result in the return of proteins to their starting materials, the amino acids, are considered. 

As the model suggests, the dietary need for amino acids is determined by the rates of depletion of the free amino acid pool by oxidation or synthesis of protein. During steady state conditions, the contribution to the free pool from dietary intake and protein breakdown should be exactly balanced by the flux out of the pool to synthesis and oxidation. Any condition that increases deposition of protein in the body or the rate of amino acid oxidation should produce an increased need for protein. For example, muscle hypertrophy is dependent on a positive balance of the protein turnover process. If synthesis of protein exceeds the catabolism of protein, then muscle mass will increase and the free amino acid pool would be depleted. Thus, a net increase in protein requires an increase in intake or a decrease in oxidation. Likewise, the same arguments hold for an increase in oxidation of amino acids. 

Although the liver is crucial in protein synthesis, it is of equal importance in amino acid metabolism and degradation. This is evidenced by the high daily turnover of amino acids, and the high proportion of amino acids that are recycled and reconstituted into new protein molecules. Over 30 g of protein are irreversibly catabolised (and hence lost) daily. The nitrogen released from the complete catabolism of amino acids can be removed by a variety of routes, but the principal... 

Protein in herbivore diets is likely to be adequate in amount to satisfy the dietary requirements for net growth of an herbivore (approx 1% of bulk diet), and perhaps also the requirement for tissue turnover The distribution of individual amino acids, however, may not even be close to those required for proper tissue growth or the turnover of existing tissues As a result, it would be expected that a substantial amount of amino acid synthesis would occur, and that the collagen of herbivores would closely reflect the isotopic composition of the herbivore s diet ... 

Protein turnover is an important process in living systems (Chapter 23). Proteins that have served their purpose must be degraded so that their constituent amino acids can be recycled for the synthesis of new proteins. Proteins ingested in the diet must be broken down into small peptides and amino acids for absorption in the gut. Furthermore, as described in detail in Chapter 10. proteolytic reactions are important in regulating the activity of certain enzymes and other proteins. 

Genetic material was defined, as were the events of transcription and translation, Genetic material contains the information that specifies the sequence of amino acids in all proteins, as well as information that regulates the rate of transcription. In studying the quantity of any protein in the cell, one must realize that the level is controlled by at least four conceptually different processes (1) the rale of RNA synthesis (transcription), (2) the rate of mRNA degradation, (3) the rate of protein synthesis (translation), and (4) the rate of protein degradation (protein turnover). 

Metabolic activation of PAHs consists of an oxidation of the rings of unsubstituted PAHs. These oxidations are carried out by mixed function oxidases of the liver which contain cytochromes P450 and P448 and require reduced nicotine adenine dinucleotide and oxygen. In this oxidation, an epoxide intermediate is formed which has been shown to have the requisite chemical reactivity to bind covalently with DNA and histones and to serve as the ultimate carcinogenic form of PAH. Administration of 3-MC to rats increased hepatic nuclear proteins and caused a turnover of protein of the endoplasmic reticulum. Studies of " C amino acid incorporation showed that 3-MC causes increased protein synthesis and reduced degradation of protein. 

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. 

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