Insulin Biosynthesis, Secretion, and Action | …

The structural basis for TnaC-mediated translational stalling wasaddressed by obtaining a 5.8-Å cryo-EM map of the ribosome stalled byTnaC and high concentrations of tryptophan (Fig. 8). The cryo-EM datashows that the nascent chain adopts a distinct conformation in the exittunnel. We applied MDFF to obtain an atomic model of the entire ribosomeand the stalling nascent chain (Fig. 8F). The model allowed us to mapthe contacts between TnaC and the exit tunnel, as well as proposepossible communication pathways that would lead to inactivation of thecatalytic center of the ribosome (the so-called peptidyltransferasecenter, or PTC). One of the main findings was that two criticalribosomal residues at the PTC adopt conformations that are incompatiblewith cohabitation by release factors, which catalyze termination ofprotein synthesis.

Friedman thyroid axes at multiple levels, FIGURE 66–1 Pathways of steroid biosynthesis.

Nutritional manipulation exerts a more long-term effect on hepatic lipogenesis and thus potentially on whole body lipid metabolism. For instance, in vivo lipogenesis is observed to be increased following the feeding of a diet with a high calorie:protein ratio but decreased following the feeding of a diet that includes fat (9). Restricted feed intake elevated fatty acid synthesis, while low-protein (12%) diets have been shown to elevate lipogenesis compared to high-protein (30%) diets (10, 11).

Insulin Biosynthesis, Secretion, and Action

The level of food intake has profound effects on the rate of incorporation of lipogenic precursors into fatty acids in ruminant adipose tissue (4, 5). Smith et al. (4) demonstrated that graded increases in the level of food intake markedly increased de novo lipogenesis. Smith and Prior (6) suggested that ATP-citrate lyase is rate limiting to the incorporation of lactate into fatty acids because of the high correlation between the intracellular concentration of citrate and the rate of lipogenesis from lactate. Studies conducted using chickens demonstrated that short-term fasting reduces lipogenesis (7), while meal size increased the proportion of glycogen synthesized by rats (8).

Mechanisms of Protein Synthesis by the Ribosome

Biosynthesis of fatty acids is strictly regulated. The primary determination of lipogenesis or lipolysis is the equilibrium between monomeric and polymeric acetyl-CoA carboxylase. Several hormones, including insulin, glucagon, glucocorticoids, epinephrine, the secondary messenger cAMP, as well as diet composition and nutrient manipulation all exert important regulatory action on lipid metabolism. However, the recent discovery that genetics play an integral part in determining the extent of fatty acid synthesis may prove to be the most beneficial breakthrough in the "War on Fat". Future investigations and studies of leptin and its method of transduction may unveil the mystery of fat synthesis and allow the development of pharmacological agents to prevent obesity.

Mechanisms of Protein Synthesis by the ..

The rate of fatty acid synthesis is controlled by the equilibrium between the monomeric and polymeric acetyl-CoA carboxylase. Control of the acetyl-CoA carboxylase enzyme involves phosphorylation-dephosphorylation reactions (3). Metabolically, this conformational change is enhanced by citrate and is inhibited by long-chain fatty acids (i.e. palmitoyl-CoA). The accumulation of citrate in the cytosol of adipose cells shifts equilibrium to the polymeric acetyl-CoA carboxylase, thus activating fatty acid biosynthesis. Palmitoyl-CoA promotes polymer disaggregation and is a primary feedback inhibitor of fatty acid synthesis.

Thyroid Hormone Synthesis | Pathway Medicine

Newly synthesized and glycosylated enters a continuously recycling pathway that concentrates most of the in intracellular membrane systems in unstimulated muscle cells.

DNA Replication and Protein Synthesis Activity - …

Similar to TnaC described above, the peptide SecM exists solely to stallthe ribosome synthesizing it. But unlike TnaC, which also requires thepresence of high levels of trytophan, SecM has an intrinsic stallingcapability. Stalling of the ribosome synthesizing SecM provides time fora downstream RNA helix on the same mRNA strand to unwind. Unwinding ofthis helix then allows for a new ribosome to bind and synthesize anew protein, SecA, a bacterial ATP-driven translocase that aids the passage ofnascent proteins across membranes in conjunction with SecY (see also ). When sufficient levels of SecA have been reached,SecA interacts with the SecM-stalled ribosome to pull on SecM, freeingit and allowing translation to resume (illustrated schematically inFig. 13). SecM, which serves no otherpurpose than to stall the ribosome, is released into the cell anddegraded.