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Transcript
Hormonal Regulation of Protein Turnover Effect of the Endocrine System Protein Turnover synthesis is energy expensive turnover rate > than for CHO or TG synthesis energy cost is 2X that of glycogen or TG synthesis and breakdown are separately regulated processes turnover rate varies (15 min – 3 wk) synthesis and breakdown affected by four proteolytic processes in skeletal muscle gender, age, exercise, amino acid availability, dietary carbohydrate, glucoregulatory hormones, intrinsic factors? Proteolysis ubiquitin-proteosome system – accounts for ~80% of total protein breakdown – proteins selected for degradation are conjugated (attached) to ubiquitin then transported to large proteasomes other proteolytic systems – lysosomes, – calpains • Ca2+ activated • initiate degradation of myofibrillar proteins (except actin, MHC) – caspases • activated by ROS, Ca2+ • can cleave actomyosin and cytoskeleton proteins Effect of exercise, amino acids, and glucose on protein turnover Rasmussen & Phillips. Exerc Sport Sci Rev, 2003 Hormonal Regulation of Protein Turnover Insulin (stimulates synthesis) – released in response to elevated blood glucose – suppresses protein degradation – inhibits ubiquitin-proteosome, calpain, and caspase systems – increases amino acid uptake – stimulates synthesis transcription and translation Lourard et al., J Clin Invest, 1992 Fedele et al., J Appl Physiol, 2000 Hormonal Regulation of Protein Turnover Cortisol (stimulates catabolism) – released in response to stress • gluconeogenesis – principal catabolic hormone • stimulates ubiquitinproteosome system – requires co-factor (e.g., exercise, muscle damage, ROS, Ca2+) • proteolysis when cortisol : insulin is >4 Van Cauter et al. Am J Physiol, 1992 Effects of glucose ingestion on cortisol:insulin during prolonged exercise Cortisol:insulin during 2 hr of exercise (70% VO2max) in postabsorptive state. Data demonstrates how strongly proteolysis is stimulated during prolonged exercise in postabsorptive state. (MacLaren et al., J Appl Physiol, 1999) Hormonal Regulation of Protein Turnover Growth hormone (stimulates synthesis mildly) – released during exercise – by itself, not a major factor of protein synthesis • greater effect on children/adolescents Insulinlike Growth Factor I (IGF-1) (stimulates synthesis) – has synergistic relationship with GH – stimulates protein synthesis and inhibits degradation • inhibits proteolytic pathways Hormonal Regulation of Protein Turnover Androgens (stimulates synthesis) – increases muscle synthesis w/ no effect on degradation – binds to androgen receptor, which stimulates androgensensitive target genes – testosterone administration increases androgen receptor numbers • also increased by resistance exercise Bhasin et al., N Engl J Med, 1996 Relation of [testosterone] and FFM Bhasin et al. Am J Physiol, 2001 Hormonal Regulation of Protein Turnover Thyroid hormone (triiodothyronine—T3) (stimulates synthesis) – stimulates protein synthesis (and RMR) – release not affected by exercise – type I fibers affected more than type II • T3 increases expression of type I MHC & SERCA – affects Vmax, relaxation time