Amino acids into tissue proteins

Insulin stimulates protein biosynthesis by a mechanism which is not directly dependent upon its action in stimulating the uptake and accumulation of amino acids by the cells. Insulin increases the incorporation of amino acids into the protein of a number of tissues, an effect which is dependent on the presence of glucose. 

The mechanism responsible for osteoporosis resulting from immobilization is not clear. One theory suggests that muscular activity stimulates osteoblastic activity in the bone. Another theory proposes that the rate of bone destruction is accelerated in osteoporosis. In immobilized innervated rat limb, there is an increased destruction in the matrix, reflected by a more rapid turnover of [ " C]glycine into the soft tissue. The increased turnover of amino acids into the protein of soft tissue is paralelled by an increased turnover by the calcium in the bone and the in the chondroitin sulfate. 

Compared to animal tissues and bacteria, very little work has been done in tiie last 10 years on protein synthesis in plants. There are, however, a few experiments to show that the incorporation of labeled amino acids into plant proteins follows a path very similar to that just described for aninfiftl cells. 

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. 

Short-term ozone exposures (45 5 pphm, 15 min) of seedlings were followed after 24 hr by non-linear reductions in chlorophyll/g fresh weight and stimulations in fresh weight/organ. The utilization of l C-protein hydrolysate by tissue discs is not only predominantly energy-dependent, but also strictly dependent with respect to inhibition or stimulation upon the time after ozonation. Uptake of labelled amino acids into the soluble pools of tissue discs is sensitive to as little as 15 min of in vivo exposure (45 5 pphm), and incorporation into insoluble protein is sensitive during 15 to 30 min, after which no further reduction is observed for up to 90 min of exposure. The reduction of amino acid influx into the soluble pools is not accountable to a reduction in amino acid tRNA charging, and is probably not due to a reduction in amino acid incorporation. 

Collagen and elastin are examples of common, well-characterized fibrous proteins that serve structural functions in the body. For example, collagen and elastin are found as components of skin, connective tissue, blood vessel walls, and sclera and cornea of the eye. Each fibrous protein exhibits special mechanical properties, resulting from its unique structure, which are obtained by combining specific amino acids into reg ular, secondary structural elements. This is in contrast to globular proteins, whose shapes are the result of complex interactions between secondary, tertiary, and, sometimes, quaternary structural elements. 

Effects on protein synthesis In most tissues, insulin stimulates the entry of amino acids into cells, and protein synthesis. 

In addition to being incorporated into tissue proteins, amino acids, after losing their nitrogen atoms by deamination and/or transamination, may be catabolized to yield energy or to form glucose. Conversely, the nonessential amino acids may be synthesized from carbohydrate metabolism intermediates and ammonia or from essential amino acids. This section is devoted to the mechanisms of such metabolic processes and their interrelationships with carbohydrate and lipid metabolic pathways. 

ADME Since metabolism and formation of active metabolites are not a concern for unmodified biopharmaceuticals, mass balance studies are uninformative. Tissue concentration of radioactivity using radioactive proteins is also difficult to interpret due to unstable radiolabel linkage, rapid in vivo catabolism, and recycling of radiolabeled amino acids into non-drug-related proteins/peptides. 

In muscle and adipose tissue, insulin promotes transport of glucose and other monosaccharides across cell membranes it al.so facilitates tran.sport of amino icids, potassium ion.s. nucleosides, and ionic phosphate. Insulin also activates certain enzymes—kinases and glycogen. synthetase in muscle und adipose tissue. In adipose tissue, insulin decreases the release of fatty acids induced by epinephrine or glucagon. cAMP promotes fatty acid release from adipose ti.ssue therefore. it is pos.sible that insulin decreases fatty acid release by reducing tissue levels of cAMP. Insulin also facilitates the incorporation of intracellular amino acids into protein. 

Transport of amino acids into cells is mediated by specific membrane-bound transport proteins, several of which have been identified in mammalian cells. They differ in their specificity for the types of amino acids transported and in whether the transport process is linked to the movement of Na+ across the plasma membrane. (Recall that the gradient created by the active transport of Na+ can move molecules across membrane. Na+-dependent amino acid transport is similar to that observed in the glucose transport process illustrated in Figure 11.28.) For example, several Na+-dependent transport systems have been identified within the lumenal plasma membrane of enterocytes. Na+-independent transport systems are responsible for transporting amino acids across the portion of enterocyte plasma membrane in contact with blood vessels. The y-glutamyl cycle (Section 14.3) is believed to assist in transporting some amino acids into specific tissues (i.e., brain, intestine, and kidney). 

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