Muscle Metabolism

• Energy Supply vs Demand:

  • energy is supplied in the form of ATP
  • ATP = energy donor
• What is energy used for?

  used for:

  • chemical work
  • mechanical work
  • transport work
• We have 2 metabolic pathways:

  • catabolic = convert substrates into energy; releases energy
  • anabolic = use energy to produce substrates; requires energy to build larger molecules; store energy
• Energy is released at controlled rate based on substrate availability and enzyme activity:

  • mass action effect = more substrate —> faster rate; more product —> slower rate
  • enzyme effect = more enzyme or increased enzyme activity —> faster rate of product formation
• Energy substrates:

  • they are fuel sources we can convert into energy
  • breakdown of substrates provides energy to synthesize ATP
  • also provides substrates that contribute to resynthesize ATP via oxidation
• Substrates:

  Fat:

  • most efficient substrate for energy storage
  • slow rate of energy production
  • release energy slowly
  • in rested state, body stores energy as fat via anaerobic reactions

  Carbs:

  • less efficient substrate for energy storage
  • high rate of energy production
  • release less energy
  • release energy quicker
• ATP breakdown:

  • ATP is broken down via hydrolysis
  • hydrolysis = chemical bonds are broken via water
  • breaking these bonds releases energy
  • ATP + H2O —> ADP + Pi + energy
  • enzyme = ATPase
• Consumers of ATP:

  • myosin ATPases
  • Ca2+ ATPases
  • Na+/K+ ATPases
• ATP and breakdown rates

  • heavy aerobic exercise = 15s
  • severe aerobic exercise = 6s
  • all-out sprint = < 2s
• Nonoxidative energy sources:

  • phosphocreatine
  • glycolysis/glycogenolysis
  • ATP resynthesized via nonoxidative processes = substrate-level phosphorylation
  • occurs in the cytosol
• Phosphocreatine:

  • energy from hydrolysis of PCr rebonds ADP and Pi to form ATP
  • enzyme = creatine kinase
  • PCr + H + ADP <—> ATP + Cr + H2O + energy
  • when ATP levels decrease (and ADP increases), CK levels increase
  • when ATP levels increase (and ADP decreases), CK levels decrease
• Glycolysis/Glycogenolysis:

  • first converse to glucose-6-phosphate
  • costs 1 ATP for glucose; 0 for glycogen
  • glucose = 2 ATP
  • glycogen = 3 ATP
• Glucose:

  • glucose + 2 ADP + 2 Pi + 2 NAD —> 2 pyruvate + 2 ATP + 2 NADH + 2 H2O + 2 H

  Glycogen:

  • glycogen + 3 ADP + 3 Pi + 2 NAD —> glycogen + 2 pyruvate + 3 ATP + 2 NADH + 2 H2O + 1 H
• Lactate formation:

  • occurs when there is excess amounts of pyruvate
  • occurs during nonoxidative processes
  • formation allows glycolysis to continue
  • enzyme = lactate dehydrogenase
  • 2 pyruvate + 2 NADH + 2 H <—> 2 lactate + 2 NAD
• What is so great about oxidative phosphorylation?

  it can sustain ATP resynthesis requirements indefinitely

  extras:

  • takes longer because it has more steps than anaerobic pathways
  • slower to reach peak; cannot resynthesize ATP as fast
  • helps extend exercise for longer
• Oxidative energy sources:

  • citric acid cycle
  • electron transport chain
  • referred to as oxidative phosphorylation
  • occurs in the mitochondria
  • oxidative system can sustain ATP resynthesis requirements once steady state is achieved
• Components of the mitochondria:

  • outer membrane (permeable)
  • inner membrane (impermeable)
  • intermembrane space (creatine kinase)
  • matrix (where citric acid cycle occurs)
  • mitochondria are found beneath the sarcolemma and between myofibrils
• Conversion of pyruvate to acetyl—CoA:

  • it is the link between glycolysis and the citric acid cycle
  • it is irreversible
  • enzyme = pyruvate dehydrogenase (PDH)
  • in oxidative phosphorylation, pyruvate becomes acetyl-CoA instead of lactate
  • 2 pyruvate + 2 CoA + 2 NAD —> 2 acetyl-CoA + 2 CO2 + 2 NADH + 2 H
• Citric Acid Cycle:

  • Second stage of carb breakdown
  • oxidizes acetyl-CoA
  • 4 electrons are removed from acetyl-CoA
  • 3 electrons added to NAD+ —> NADH
  • 1 electron added to FAD —> FADH2
  • energy from oxidization is stored in the reduced coenzymes (NADH and FADH2)
  • 3 NAD + FAD + GDP + Pi + acetyl-CoA —> 3 NADH + FADH2 + GTP + CoA + 2 CO2 + 3 H
• Per 1 acetyl-CoA:

  • 3 NADH
  • 1 FADH2
  • 1 CO2
  • 1 ATP
  • *** must multiply everything by 2

  at the end:

  • 10 reduced enzymes
  • 6 CO2 molecules
• Malate-aspartate shuttle:

  • translocates electrons from glycolysis across inner membrane of mitochondria
  • shuttles NADH across the inner membrane because it is impermeable
  • malate carries NADH across
• Electron transport chain:

  • proteins and molecules in inner membrane that transfer electrons from NADH and FADH2 from one member of the chain to another
  • series of redox reactions
  • energy released in the chain transfers protons (H) from matrix to intermembrane space
  • protons create an electrochemical gradient
  • energy is harnessed to create ATP
  • O2 at the end of the chain where it accepts electrons to form water
  • if there is no O2 then the ETC will stop running
• 3 stages of oxidizing carbohydrates:

  • glycolysis
  • citric acid cycle
  • electron transport chain

  C6H12O6 + 6 O2 + 32 ADP + 32 Pi —> 6 CO2 + 6 H2O + 32 ATP
• Oxidative phosphorylation has 3 prerequisites:

  • availability of reducing agents NADH and FADH2
  • presence of terminal oxidizing agent (oxygen)
  • sufficient quantity of enzymes and metabolic machinery in tissues to make energy transfer reactions “go” at appropriate sequence and rate
• NADH:

  • 2 NADH + 2 H + 5 ADP + 5 Pi + O2 —> 2 NAD + 5 ATP + 7 H2O

  FADH2:

  • 2 FADH2 + 3 ADP + 3 Pi + O2 —> 2 FAD + 3 ATP + 5 H2O
• Creatine kinase and PCr shuttle:

  • CK/PCr energy shuttle connects sites of ATP production with sites of ATP utilization
  • CK in intermembrane space and cytosol
• PCr and oxidative phosphorylation:

  • when you increase PA intensity, you use PCr stores in a manner reciprocal to VO2 levels
  • takes longer to reach steady state at higher intensities —> means we must rely on non-oxidative stores in this initial exercise period
  • therefore, PCr falls more because it is also used as a non-oxidative store mechanism
• What does our body not store a lot of?

  Carbohydrates
• How do we mainly store energy?

  As fat
• How do we metabolize fatty acids?

  via beta-oxidation
• Beta-oxidation is part of which energy source?

  oxidative energy source

  • therefore we synthesize ATP via oxidative phosphorylation
  • in the mitochondria
• types of fat:

  • fatty acids = oxidize or form of fat
  • triglycerides = glycerol + 3 fatty acids stored in fat cells
  • phospholipids = make up membranes
  • sterols = like cholesterol; transporters
• Storage of fat:

  • adipose tissue (as triglycerides); beneath the skin (subcutaneous)
  • muscles (aka: intramuscular triglycerides); can be accessed quickly
• Transport of fat:

  • in blood = fat attaches to protein (albumin)
  • across sarcolemma = fatty acid translocase
  • into mitochondria = carnitine transport system
• Breakdown of fat:

  • lipolysis = add water (hydrolysis) to break triglycerides into their components
  • oxidation = of fatty acids and glycerol to produce ATP
• Fat sources during exercise:

  • fat travels from adipose tissue to blood to muscle
  • from adipose tissue to blood, triglycerides are broken down into glycerol and 3 fatty acids (lipolysis)
  • the body chooses where it takes fat from when you’re exercising
• Lipolysis:

  • fatty acids must be released from triglycerides and activated to become fatty acyl CoA before it can be oxidized in the mitochondria
• Lipolysis:

  step 1:

  • hydrolysis of triglycerides
  • enzyme = hormone sensitive lipase
  • triglyceride + H2O —> 3 fatty acids + glycerol

  step 2:

  • transformation of fatty acids
  • enzyme = acyl-CoA synthetase
  • fatty acid + ATP + CoA —> fatty acyl-CoA + AMP + PPi
• where does lipolysis occur?

  the cytosol
• Transporting fatty acyl-CoA:

  • must be transported into mitochondrial matrix because it is impermeable to CoA and its derivatives
  • transport via proteins and small molecules
  • molecules = carnitine
  • fatty acids attach to carnitine (become acyl carnitine) and cross inner membrane through carnitine acylcarnitine translocase (detach at the end and rebecome fatty acyl-CoA and carnitine)