Phosphorylation resulting in activation/deactivation of proteins in the Akt-mTOR pathway has been shown to be critical in the regulation of contraction-mediated increases in protein synthesis (). Other contraction-dependent signaling pathways, such as the MAPK pathway, may also be involved in regulating contraction-mediated translational control (, ). Phosphorylation of p38 MAPK can affect transcription factors such as peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) (, , ). As a primary regulator of mitochondrial biogenesis, PGC-1α coordinates transcriptional activity and assists in coordinating the transcription of mitochondrial and nuclear DNA for mitochondrial biogenesis (, ). Higher-intensity aerobic exercise has been demonstrated to result in a greater increase in the mRNA abundance of PGC-1α compared with lower-intensity exercise (), but whether aerobic exercise intensity alters rates of mitochondrial protein synthesis (MitoPS) is unknown.
The group-mean 13C-KIC-enrichments, used as a valid estimate of the protein synthesis precursor pool 13C-leucine-enrichment , , were found to be slightly higher towards the end of the tracer-incorporation period than in the beginning. Such minor fluctuations and changes in tracer steady state are often seen in tracer studies applying the primed-continuous infusion protocol, as the perfect priming is hard to calculate. When using 13C-leucine as a tracer and venous 13C-KIC as a derived estimate of the intracellular tracer abundance, those are thought to be equilibrated during such minor drifts in tracer abundance and thus are ascribed to reflect the actual precursor enrichment. Thus, by using a weighted mean of the precursor pool enrichment the minor drift towards higher enrichments is not supposed to violate the underlying assumptions for the FSR calculations.
Protein folding in the endoplasmic reticulum Protein synthesis
where E2b and E1b are the bound protein enrichments at times 2 and 1, respectively, and Ep is the average enrichment of the precursor, intracellular phenylalanine, during steady state. Since participants were “tracer naïve”, the baseline preinfusion blood sample enrichment represents the naturally abundant 13C enrichments and was used for E1b to determine resting FSR. In this calculation, we used an incorporation time from 30 min after the start of the infusion to the time of the biopsy, which has been previously validated ().
Detailed description how muscle protein synthesis is measured ..
In summary, it is very common to see studies reflecting both increased protein synthesis and hypertrophy with a myriad of rep ranges and resistance training protocols. The extent of hypertrophy may be a direct reflection in increased translational efficiency or an increase in pre-translational abundance of mRNA. The differences may be owing to the training status of the individual and not necessarily the rep range used in the resistance training routine. Although it appears that the rep range will have an impact on metabolic shifts in isoform content this does not change the sarcoplasmic vs. contractile protein synthesis ratio but merely dictates which fiber type will experience the greater amount of hypertrophy.
Guide to Muscle Protein Synthesis
KA modulates the activity of transcription factors, such as nuclear receptors and HMG (High Mobility Group)-containing proteins, influencing their dimerization or DNA-binding properties. PKA also regulates Gli3 (Gli-Kruppel Family Member-3) under the influence of Hedgehog signaling. Function of Gli3 is similar to that of Drosophila gene CI (Cubitus Interruptus) activity. In this case phosphorylation stimulates a specific cleavage of Gli3 which transforms the protein from an activator to a repressor. However, proteins like PKIs (Protein Kinase Inhibitors) and Mep1B (Meprin-A-Beta) down regulate PKA activity to prevent aberrant gene expression. In mammalian cells, including human, PKA regulate a huge number of processes, including growth, development, memory, metabolism, and gene expression. Failure to keep PKA under control can have disastrous consequences, including diseases such as cancer. Drugs based on inhibiting PKA activity are under development for treating disease, so understanding how cAMP accomplishes this task is of interest to life scientists (Ref.14 & 15).
Sarcoplasmic Hypertrophy and Rep Range - WeighTrainer
Serine 21 in GSK3Alpha (Glycogen Synthase Kinase-3-Alpha) and Serine 9 in GSK3Beta (Glycogen Synthase Kinase-3-Beta) are also physiological substrates of PKA. PKA physically associates with, phosphorylates, and inactivates both isoforms of GSK3, thus prevents Oncogenesis and neurodegeneration. HSL (Hormone-Sensitive Lipase), an important enzyme of lipolysis, is also phosphorylated by PKA. PKA-phosphorylated HSL rapidly translocates and adheres to the surface of lipid droplets. It is this translocation and not HSL activation that accounts for the strong lipolytic enhancement following PKA activation. PKA interferes at different levels with other signaling pathways. Inactivation of PTP (Protein Tyrosine Phosphatase) results in dissociation from and consequent activation of ERKs. Inactivation of PCTK1 (PCTAIRE Protein Kinase-1) and APC (Anaphase-Promoting Complex) helps to maintain control cell proliferation and anaphase initiation and late mitotic events, respectively, thereby checking the degradation cell cycle regulators. Gcg binds to GcgR/GN-Alpha proteins on the surface of liver cells and triggers an increase in cAMP production leading to an increased rate of Glycogenolysis by activating PHK (Phosphorylase Kinase) via the PKA-mediated cascade. PHK further activate PYG (Glycogen Phosphorylase), which converts Glycogen to Glucose-1-Phosphate. Phosphoglucomutase then transfers phosphate to C-6 of Glucose-1-Phosphate generating Glucose-1,6-phosphate as an intermediate. The phosphate on C-1 is then transferred to the enzyme regenerating it and Glucose-6-Phospahte is the released product that enters Glycolysis. This is the same response hepatocytes have to Epinephrine release through the ADR-Alpha/Beta. PKA further inhibits GYS (Glycogen Synthase) leading to seizure of energy consuming process like Glycogen Synthesis. PKA phosphorylates GRK1 (G-Protein-Dependent Receptor Kinase-1) at Ser(21) and GRK7 (G-Protein-Dependent Receptor Kinase-7) at Ser(23) and Ser(36). Phosphorylation of GRK1 and GRK7 by PKA reduces the ability of GRK1 and GRK7 to phosphorylate Rhodopsin (Ref.10, 12 & 13).