Rates of protein synthesis--a review.

The rates of protein synthesis can be measured by a variety of methods including pulse labeling, massive precursor administration, Scornik method, continuous feeding of labeled precursor, infusion, and pellet implantation. Each technique has some advantages and disadvantages. Massive precursor administration and infusion are the most widely used. The advantage of massive precursor administration is its simplicity, however, the amino acid concentration used is much higher than physiological levels. Infusion, however, is much more complicated as a technique and requires complicated calculations. The synthesis rates can also be calculated from degradation curves. Some of the above techniques can be used both in vivo and in vitro, and also for different organs (Shahbazian et al. (1987), Int. J. Dev. Neurosci., 5: 39-42). The brain has rapid rates of protein synthesis both in vivo and in vitro, the latter being much lower for adults.

Rates of protein synthesis in brain and other organs.

We previously found a decrease in protein synthesis in brain during development, which was much greater as measured in brain slices than in brain in vivo. In the present work such changes in brain were compared to those in other organs. With measurement of incorporation of flooding doses of [14C]valine into proteins of organs, the highest synthesis rate in the adult animal in vivo was found in liver (2.2%) followed by kidney (1.8%), spleen (1.6%), lung (1.0%), heart (0.7%), brain (0.6%) and muscle (0.5%). In immature animals the synthesis rate was highest in spleen (2.6%) followed by liver (2.4%), kidney (1.7%), lung (1.6%), brain (1.5%), heart (1.1%), and muscle (0.9%). Protein synthesis in slices from each tissue proceeded at lower rates than in vivo, especially in adults. The tissue affected the most by the preparation of the slices was muscle.

Amino acid incorporation in relation to molecular weight of proteins in young and adult brain.

Rates of protein synthesis were studied in immature and adult rat brain tissue. After an amino acid incorporation period, in vivo or in incubated slices from brain, the soluble protein was fractionated according to molecular weight by column chromatography. In examining soluble whole proteins, no direct correlation between molecular weights and synthesis rates could be established; the highest synthesis rates were found in fractions around 70,000 MW and below 10,000. Incorporation into the subunits after fractionation by SDS gel electrophoresis was proportional to subunit molecular weight, with rates of incorporation into the largest subunits being the highest. The results suggest a relationship between turnover rate and structure of subunits of brain proteins.

Rates of amino acid incorporation into particulate proteins in vivo and in slices of young and adult brain.

Incorporation of a flooding dose of valine into brain proteins was measured in vivo and in brain slices, according to subcellular fraction and to solubility. In particulate fractions in vivo in the immature brain, soluble cytosol proteins had the highest synthesis rates (2.0% per hr), followed by microsomes (1.7%), mitochondria, nuclei (1.4%), and synaptosomes (0.85%). In adult, the rates were about half of those of immature animals except for microsomes, which were the same. In young, rates of incorporation into particles in brain slices were about 80% of in vivo rates, and adult rates were 10-20% of the in vivo rates. When brain proteins were fractionated into four groups--isotonic soluble, hypotonic soluble, Triton X-100 soluble, and the remainder solubilized in 0.2% SDS--in both young and adult brain in vivo, the isotonic fraction had the highest rate of protein synthesis, followed by the Triton-soluble fraction, the SDS-soluble fraction, and the hypotonic fraction. Also, with this method of separation in vitro rates for immature brain were 10-20% lower than in vivo rates, while in vitro adult rates were 80-90% lower. The results indicate that the most proteins are synthesized at a higher rate in the immature brain, and that the difference between in vivo and brain slice protein synthesis is not as great in the immature as in the mature brain in all the fractions examined.

Regional and cellular differences in rat brain protein synthesis in vivo and in slices during development.

We compared the rate of protein synthesis in immature and adult rat brain in vivo to that in brain slices. After the incorporation of a flooding dose of [14C]valine, in vivo and in brain slices, the label in proteins was measured in CNS regions and in neuron- and glia-enriched fractions. In regions in vivo in the adult, incorporation rates in corpus callosum were lower than in other regions, which were similar; in the young, cerebellum showed the highest rates and hypothalamus and cord the lowest. Since hypothalamus and cord were low in the young, there was no change during development in these two areas; in other areas incorporation rates in young were 2-3 times higher than in adult brain proteins. Incorporation rates in slices were lower than in vivo. In the young, cerebellum, olfactory bulb, and cord were close to in vivo, and other areas in slices from young incorporated at 60-90% of in vivo rates. In adult slices incorporation was 5-15% of that in vivo except in olfactory bulb, where it was 30%. In the cellular fractions, incorporation in vivo in young was close in the neuronal and glial fractions; in adults incorporation rates in neurons were higher, as the decrease in development was less in neurons than astrocytes. In slices in young, astrocytes incorporated amino acids at 100% of the in vivo rates, neurons at 60%; in adult slices, incorporation was at only 4-7% of the in vivo rate. The results show that developmental changes in protein metabolism occur in all brain areas and brain cells, with metabolic rates in young 2-3 times that in adult.(ABSTRACT TRUNCATED AT 250 WORDS)

Selenium heterocycles XVIII: Synthesis and antibacterial activity of 4-substituted (1,2,3-selenadiazol-5-yl) carbamic acid esters and their sulfur analogs.

4-Substituted (1,2,3-selenadiazol-5-yl)carbamic acid esters and their sulfur analogs were prepared from the Curtius rearrangement of the corresponding carboxazides. None of the compounds showed significant antibacterial activity.