Muscle at Rest/Exercise - Abali 3/17/16 Flashcards
health adv of regular exercise
- lower CVD risk
- HDL/LDL/TAG
- obesity
- bp
- lower blood glucose (better response to insulin)
- lower stress
- higher immune fx (to a pt, past which it can ding your immune fx )
AMP-activated protein kinase pathway
stimulation of energy production in low energy/stress states
- cell stress causes energy consumption to outpace energy production
- ATP falls, ADP rises
- ADP → ATP [adenylate kinase]
- rise in AMP + drop in ATP → activation of AMPK
- AMPK stimulates catabolism (more ATP) and puts a hold on ATP-consuming processes (synth pathways)
AMP kinase
(AMPK)
+ : AMP
- : ATP
pathways it affects:
- upreg GLUT4 activity → more glucose transport into cells
- upreg sk muscle FA oxidation
- downreg synthesis: TAG/glycogen/protein/chol/FA/insulin secretion
recall: hormonal reg of glycolysis/gluconeogenesis
insulin: activates glycolysis, inhibits gluconeogen
- dephosphorylates PFK2 → fructose 2,6 bisphosphatase made
- F2,6BP → activates PFK1 (activates glycolysis)
- F2,6BP → inhibits F1,6BPase (no gluconeo)
glucacon: inhibits glycolysis, activates gluconeogen
- phosphorylates PFK2 → NO fructose 2,6 bisphosphatase made
- no F2,6BP → PFK1 not activated (no glycolysis)
- no F2,6BP → stops inhibition of F1,6BPase (activates gluconeo)
effect of epinephrine on glycolysis
accelerates glycolysis in muscle
epi → P of glycogen phosphorylase, more glycogen degradation → more F6P → more F2,6P [PFK2], activating glycolysis
- F2,6P is allosteric activator of PFK1, glycolysis
epi inhibits glycolysis in liver
regulation of beta oxidation of FA in muscle
occurs at level of fatty acyl CoA entry into muscle mitochondria
malonyl CoA inhibits CPT1
low energy state indicated by rise in AMP → activation of AMP-protein kinase
high energy/low AMP, AMPK inactive
- ACC (acetyl CoA carboxylase) converts acetyl CoA into malonyl CoA → inhibits CPT1, entry of fatty acyl CoA for beta ox
low energy/high AMP, AMPK active
- ACC downreg’d
- MCoADC (malonyl CoA decarboxylase) upreg’d, converts malonyl CoA into acetyl CoA → undoes inhibition of CPT1, clears the road for fatty acyl CoA
- muscle now able to generate ATP from FAs!
adipose tissue: glyceroneogenesis
adipose tissue doesnt have glycerol kinase (cant pick up glycerol from TAGs in circ)
- needs to make its own glycerol3P through glycolytic intermediates
during lipolysis (stimulated by epi, cortisol), HSL is active → glycolysis is inhibited → DHAP not available to make glycerol3P!
enter. ..glyceroneogenesis (fx: convert pyruvate → DHAP)
* reason why adipose cells express pyruvate carboxylase and PEP-CK even though they dont make glucose!
why do you need glyceroneogenesis to occur when you have lipolysis?
(seems counterintuitive)
TGs and FAs shuttle between liver and adipose tissues to maintain high lipid turnover rate in blood: FA-TG cycle
adipose TG broken down in excess of amount needed → liver repackages FA in VLDL, sends it back to adipose tissue
the process…
- uses energy (but no more than 5%)
- conserves FAs not used for ox
glyceroneogenesis allows you to pick up and store the excess FAs released during exercise or fasting
how is blood glucose maintained over long periods of exercise?
liver glycogenolysis
liver gluconeogenesis
- initially, much greater contribution from glycogenolysis than from gluconeogenesis
- over several hours, becomes almost 50:50 contribution
alanine-pyruvate cycle
net transport of nitrogen from BCAAs (Iso, Leu, Val) to liver, but no net production of glucose
- in liver, Ala → NH3 + pyruvate
- pyruvate converted to glucose, heads back to muscle cell and is recycled through
will happen during strenuous exercise and also during starvation
biological energy systems used by muscle
phosphagen system (creatine phosphate)
- anaerobic
- bursts of heavy activity (exhausted in ~15s)
- active at the start of all exercise (regardless of intensity)
glycolysis
- breakdown of carbs (either stored glycogen or delivered through circ)
- fast (anaerobic) and slow (uses oxphos)
oxidative system
- primary source of ATP at rest/low-int exercise
- uses mainly carbs (oxphos) and fats (beta ox)
**all three active at any given time; extent to which each is used depends on activity intensity and duration
energy system selection
phosphagen system: short duration, high intensity
glycolytic system: short-med duration, mod-high intensity
oxidative system: long duration, low intensity
- both beta-ox and glycogen through beta ox (?)
rate of energy demand and power output will determine when you incorporate one system or another
phosphagen system
used for short bursts of high intensity training
active at the start of all exercise regardless of intensity (exhausted in <30s)
creatine is a reservoir of high-egy P that can be used to get ADP → ATP
- carries high egy P from mitochondria to myosin filaments where ATP is used for contraction
- ADP + creatine phosphate → ATP + creatine [creatine kinase]
creatine stocks
- muscle only stores a small amt; working out more increases size of muscle creatine store
- reformation of PC requires ATP - only occurs during recovery
utility of anaerobic glycolysis to a muscle cell in high exertion
rate of ATP production from glycolysis is approx 100x as fast as oxphos!
fast glycolysis: pyruvate → lactic acid
- energy produced RAPIDLY
slow glycolysis: pyruvate moves to mito for oxphos
ranking of ATP generating processes by…
- rate of energy production
- amt of ATP produced
inverse relationship: fastest rate = lowest yield and vice versa
in order of fast → slow (or low yield → high yield):
- phosphagen
- fast glycolysis
- slow glycolysis
- oxidation of carbs
- oxidation of fats/proteins
