Bioenergetics Flashcards
What is metabolism and how is it regulated
- Sum of all chemical reactions that occur in the body, anabolic (synthesis of molecules) and catabolic (breakdown of molecules)
- Regulated by enzymatic activity
What is bioenergetics
- Converting foodstuffs (fats, proteins, carbohydrates) into energy
Describe cell structure
- Cell Membrane: Phospholipid bilayer (lipid soluble substances), fluid mosaic, semipermeable, regulates passage of materials (secretion / absorption), proteins embedded, interacts with environment
- Nucleus: Genetic information (DNA - linear chromosomes), controls shape and activity through protein synthesis, exports genetic information as RNA via the nucleolus / nuclear pores
- Cytoplasm: Gelatinous helix that surrounds the nucleus, membrane bound organelles suspended, chemical reactions, cytosol (semi-fluid matrix)
- Mitochondria: Double walled (inner wall = membranous cristae) partition matrix in-between (DNA / ribosomes), divides independently, site of cellular respiration / metabolism, semi-autonomous
What is energy storage and ATP
- Storage: Energy is stored in chemical bonds within molecules and released when these bonds are broken
- ATP: Adenosine triphosphate, energy currency of cell, energy rich phosphate bonds, made up of three elements (adenine, ribose and phosphate)
- Adenosine diphosphate + inorganic phosphate forms adenosine triphosphate
What are enzymes and two types
- Complex protein structures, catalysts that regulate speed of reactions by lowering the activation energy (Ea), formation of an enzyme substrate complex, remains unchanged (not consumed)
- Kinases: Add phosphate groups to the substrates (creatine kinase, ATPase)
- Dehydrogenases: Remove hydrogen from their substrate (lactate dehydrogenase)
What are factors that affect enzyme activity
- Temperature: Small rise in body temperature increases enzyme activity, exercise results in increased body temperature, large increases in temp can result in decreased activity (exercise)
- pH: Change in pH reduces enzyme activity, each enzyme has an optimal pH range, acid during exercise
What are rate limiting enzymes / modulators of them
- Control of bioenergetics, regulate rate of pathways
- Increase ‘opportunity’ for reaction to progress (increase number of enzymes)
- Switch off enzymes when not required
- Modulators: Levels of ATP and ADP + Pi , high levels of ATP inhibit ATP production, low levels of ATP and high levels of ADP+Pi stimulate ATP production
What is an energy system
- Function to restore ATP (or similar high energy phosphates), energy for can be provided by ATP-PC, glycolysis, oxidative phosphorylation / ETC, beta oxidation / ETC
- No one energy system provides all of the energy for ATP regeneration
- Involves varying contributions for each system
What is ATP hydrolysis and repletion
- Breakdown (catabolic), ATP → ADP + Pi + free energy for biological work, enzyme ATPase breaks the chemical bond of ATP
- Repletion: Occurs very rapidly via ATP-PC (phosphocreatine), lactic acid system and aerobic system, enough for ~ 1sec maximal contraction contained within the cell
What is the phosphocreatine system
- PC, PCr, CP, CrP
- Energy rich phosphate bond, most readily available fuel source for muscle contraction (stored within muscle fibre
- ~5-10 seconds worth of muscle contraction
- ATP hydrolysis catalysed by creatine kinase during exercise
- ATP-PC system, immediate source of ATP, PC + ADP + creatine kinase → ATP + C
- Rapid due to short uncomplicated reaction, doesn’t require O2, easily accessible
- Used in throwing, jumping, sprinting, power lifting, events lasting < 10s
- Regulated by creatine kinase (CK), activated by increase ADP (instantly triggers breakdown of CP to replenish ATP), inhibited by increased ATP
What is glucose vs glycogen and transferals between
- Glucose: C6H12O6, glycogen is a more compact storage form of glucose, blood glucose interacts with muscle glycogen during glycolysis to form pyruvate / lactate
- Glycogenesis: Formation of glycogen from glucose
- Gluconeogenesis: Formation of glycogen from substrates other than glucose
- Glycogenolysis: Breakdown of glycogen to glucose, occurs one glucose at a time
What is glycolysis and what does it produce
- Anaerobic pathway, breakdown of glucose or glycogen to form pyruvate, occurs within the sarcoplasm (outside the mitochondria)
- Ubiquitous, substrate level phosphorylation
- Releases a small amount of energy stored in glucose, much energy still locked up in pyruvate (C-H)
- Preparatory / payoff phase
- Glucose + 2 NAD+ + 2 ADP + 2 Pi → 2 Pyruvate + 2 NADH + 2 H+ + 2 ATP
What are the steps of glycolysis
Preparatory Phase:
- Energy investment, phosphorylation of glucose (6C)
- Glucose-6-phosphate (via hexokinase, use ATP)
- Fructose-6-phosphate
- Fructose-1,6-biphosphate (via phosphofructokinase, use ATP)
- Glyceraldehyde-3-phosphate (3C)
- Used: 2 ATP molecules, 1 glucose and 2 NAD+
Payoff Phase:
- Energy production, glyceraldehyde-3-phosphate (3C) converted to pyruvate (3C)
- Products: 2 NADH (re-oxidised to NAD+), 4 ATP (2 ATP net) and 2 pyruvate
What are electron carrier molecules
- Energy Carriers: Transport H and associated E, to mitochondria for ATP generation (aerobic) or to convert pyruvic acid to lactic acid (anaerobic)
- NAD: Nicotinamide adenine dinucleotide, NAD+ + H → NADH, NADH produced in glycolysis must be converted back to NAD+
- Shuttling H+ into the mitochondria via specific transport system in mitochondrial membrane
- FAD: Flavin adenine dinucleotide, FAD + 2H → FADH2
Define aerobic vs anaerobic
- Anaerobic: Formation of ATP without the use of O2 (ATP-PC and glycolysis), cytoplasm, shorter energy production
- Aerobic: Production of ATP using O2 as the final electron acceptor (TCA, ETC), oxidative, mitochondria, longer energy production (60sec)
What is our immediate source of energy
- The immediate source of energy for muscular contraction is the high-energy phosphate ATP. ATP is degraded via the enzyme ATPase as follows: ATP + ATPase → ADP + Pi + energy
How do muscle cells produce ATP
- Produce ATP by any one or a combination of three metabolic pathways
- (1) ATP-PC system
- (2) glycolysis
- (3) oxidative formation of ATP
Describe glycolysis activity at rest vs sprinting
- Rest: Not very active at rest, only way RBC can produce energy is through glycolytic pathway
- Sprint Activity: During sprint activity glycolysis must occur several hundred times faster than at rest
How is glycolysis regulated (4 RLE)
Glycogen Phosphorylase:
- Facilitates conversion of glycogen to glucose
- Activated by high ADP, Ca, epinephrine and inhibited by high ATP and FA
Hexokinase:
- Facilitates conversion of blood glucose to glucose-6-phosphate, high affinity for glucose, inhibited by high FA and its product (glucose-6-phosphate)
- ATP required
- Prefer to use glycogen to produce glucose-6-phosphate (inhibits HK and ‘spares’ blood glucose / ATP)
Phosphofructokinase (PFK):
- Facilitates conversion of fructose-6-phosphate to fructose 1,6 biphosphate
- Key rate limiting step
- Activated by high fructose-6-phosphate and ADP and low creatine phosphate
- Inhibited by high H, citrate (krebs cycle), ATP and FA
Pyruvate Kinase:
- Final glycolytic step, activated by high fructose-6-phosphate, inhibited by ATP, conversion of glyceraldehyde-3-phosphate into pyruvate
What is the function and steps of the lactate system and when is it utilised
- Supplements ATP-PC system when O2 supply rate is inadequate for the energy demand, valuable fuel source
- Produced in quantities equivalent to the amount of H+
- Re-oxidise NADH, consume H (increase pH) and permit continued ATP production from glycolysis
- Pyruvate → lactate (transported in blood) → liver → pyruvate → glucose / glycogen, reuse lactate and recovery of glucose
- Primarily recruited for max efforts lasting 20-50s
How is lactate removed following exercise
- 10% sweat and urine, 20% gluconeogenesis in the liver and 70% re-oxidised to pyruvate then enters the TCA cycle
- Often occurs in non working muscles and heart
- Moderate Exercise: 30-50% of VO2 max, improves recovery by maintaining high BF and oxidative functioning of working musculature
- Intense Exercise: >AT, >70% of VO2 max) may result in further lactate production, not suitable recovery
What is TCA cycle and facilitation of energy carriers
- Complete oxidation of CHO, fats and sometimes proteins for energy, produces 2 ATP, 6 NADH, 2 FADH2, 9 steps
- Oxidation: The removal of H+ from a compound or the addition of O to it
- Reduction: Addition of H+ or removal of O
- Energy Carriers: NAD+ and NADH facilitate redox reactions without being consumed, they are recycled, allows many different donors and acceptors to interact, coenzyme acts as intermediary
What is the priming step of TCA cycle
- Priming and oxidation of pyruvate (3 C) to create acetate (2 C), binds with coenzyme A to produce acetyl CoA, CO2 and 2 NADH
What is the process of TCA cycle
- Acetyl CoA (2 C) combines with oxaloacetic acid (4 C) to produce citrate / citric acid (6 C)
- Subsequent decomposition / oxidation / breaking down of citrate, produces 2 CO2, 2NADH (1-4)
- Production / regeneration of oxaloacetic acid, rearranging, produces 1FADH2 and 1NADH (5-9)
- Transfers high energy e- to carriers, harvested e- directed to ETC to drive ATP synthesis
What is the ETC
- Oxidative phosphorylation of NADH and FADH2 to ATP produced in glycolysis and citric acid cycle via a series of carriers (cytochromes)
- Produces 25 ATP (from 10 NADH), 3 ATP (from 2 FADH2)
H+ and electrons are accepted by O2 to form metabolic water - Multi protein complexes and mobile carriers in the inner mitochondrial membrane / cell membrane of bacteria
- Each compound in the sequence has a higher affinity for electrons
What are the steps involved in ETC
- Stimulates one directional pumping of H across the inner mitochondrial membrane, establishes a proton gradient, excess H+ makes one side of membrane positively charged
- As H+ is transported back across the membrane, energy is released to form ATP (chemiosmosis) and used by ATP synthase to generate ATP
What is chemiosmotic energy coupling
- Proton gradient for ATP synthesis established across a membrane
- Must contain proteins that couple the “downhill” flow of electrons in the electron transfer chain with the “uphill” flow of protons across the membrane
- Membrane must contain a protein that couples “downhill” flow of protons to the phosphorylation of ADP
Provide a summary of products and RLE in glycolysis, pre-TCA, TCA and ETC
- Glycolysis: 2x pyruvate, 2x ATP and 2x NADH, phosphofructokinase
- Pre-TCA Cycle: 2x NADH
- TCA Cycle: 2x ATP, 6x NADH and 2x FADH2, isocitrate dehydrogenase
- ETC: 25 ATP (10 NADH), 3 ATP (2 FADH2) / metabolic water, overall 32 ATP, cytochrome oxidase
What is fat metabolism and its efficiency
- ATP Production: Varies with the length of the Fatty Acid (FA) chain, steric acid 18 carbon chain = 147x ATP and palmitic acid 16 carbon chain 130x ATP
- β Oxidation: FA broken down to acetyl CoA 2 C at a time, 1 ATP used, 1x FADH2 and 1x NADH generated, then enters into TCA cycle
- Efficiency: Less efficient than glucose, 15% more O2 required for FA oxidation
How is fat metabolism regulated
- FA utilised for energy by muscle come from triglyceride stored in muscle, body fat and circulating in blood stream
- Lipase’s split FA from glycerol portion of TG
- Activated by hormones, high Ep, NorEp, cortisol and glucagon and low insulin
- Increase in SNS activity, increased release of FA and TG stores
- Insulin decreases during prolonged exercise, exercise lasting >1hr blood FA conc may increase by 5x
How is metabolic water produced in ETC
- The end result of the electron transport chain is the formation of ATP and water
- Water is formed by oxygen-accepting electrons; hence, the reason we breathe oxygen is to use it as the final acceptor of electrons in aerobic metabolism
How do aerobic and anaerobic metabolisms interact
- Energy to perform exercise comes from an interaction of anaerobic and aerobic pathways
- Shorter the activity (high intensity), the greater the contribution of anaerobic energy production
- Long-term activities (low to moderate intensity) utilise ATP produced from aerobic systems
What are ways of measuring aerobic capacity and the limitations
VO2max:
- Maximal rate at which cells can utilise oxygen
- Higher VO2max increases aerobic capacity
Steady State:
- Stable VO2, HR and Ve
- Takes at least 2-3 mins for O2 consumption to stabilise
- HR is stable within 4 bpm
- VO2max is stable oxygen consumption
Blood Lactate:
- Marker of glycolytic energy production, allows glycolysis to continue
- Accumulates due to hypoxia, high NADH, recruitment of fast twitch muscle fibres
Limitations:
- Performance is limited by O delivery and utilisation
- Fick: VO2 = (SV)(HR)(a-vO2)
What is critical power
- Indicator of training intensity
- The maximal power output that can be maintained for an extended period of time without fatigue
- Predict maximal work rate
- Corresponds to highest metabolic power output
- Could theoretically be maintained indefinitely
- Unlimited in capacity, limited in rate
What is W’
- Total amount of work that can be achieved above CP
- Changes with oxygen availability
- Decreases in hyperoxic environments and at high altitude
Why is carbohydrate metabolism a primary fuel source during exercise
- Primary fuel source for short duration, incremental or high intensity exercise, major substrate used at the onset of low to moderate intensity exercise
- During prolonged work (>30 min) there is a gradual shift from carbohydrate metabolism towards an increasing reliance on fat as a fuel substrates
How is carbohydrate metabolism regulated
- Availability of NAD+, O2 availability, H+ concentration (inhibits PFK) and increased ADP and Pi stimulate glycolysis
- Epinephrine is released during periods of high stress or heavy exercise, stimulates glycolysis and promotes carbohydrate metabolism
What is blood glucose homeostasis
- Plasma glucose maintained through four processes
- Mobilisation of glucose from liver glycogen
- Mobilisation of FFA from adipose tissue (spares blood glucose)
- Gluconeogenesis from AA, lactic acid, and glycerol
- Blocking the entry of glucose into cells (forces use of FFA as a fuel)
- During exercise it is controlled by hormones, fast-acting (insulin, glucagon epinephrine, norepinephrine) and slow-acting (cortisol, growth hormone)
What is insulin vs glucagon
- Insulin: Increases cellular uptake of glucose, declines during exercise of increasing intensity and duration, a decrease will increase amount of glucose in the blood
- Glucagon: Increases blood glucose, increased mobilisation of liver glycogen, increased liver glucose output and increased sensitivity of the liver to epinephrine
How does fat metabolism contribute to fuel supply and how is it regulated
- First fat (triglyceride) must be broken down via lipase into FFA, then metabolised via b-oxidation into 2 C chains and oxidised in TCA cycle
- Epinephrine, norepinephrine, glucagon increase lipase activity promote lipolysis
- Insulin: Inhibits lipase activity, decline in insulin during longer duration exercise results in increased FFA and glycogen sparing
- Lactate: High levels promote recombination of FFA and glycerol to form fats thereby decreasing the available FFA as fuel
- Lipolysis is a slow process, occurs only after several minutes of exercise
How does protein metabolism contribute to fuel supply
- Proteases may become active in prolonged exercise
- Skeletal muscle can directly metabolise some AA with help of proteases
What occurs when one goes above CP
- Steady state is unable to be attained
- [PCr] decreases (increase glycolytic / TCA)
- VO2 max increases (increase SV, Q, a-vO2)
- Muscle pH decreases (buffer)
- Increased anaerobic contribution to energy production
- Increase HR / ventilation
How is plasma glucose maintained during exercise
- Increasing liver glycogen mobilisation
- Using more plasma FFA, increasing gluconeogenesis, and decreasing glucose uptake by tissues
- The decrease in plasma insulin and increase in plasma glucagon, E, NE, GH, and cortisol
Why does plasma FFA concentration decrease during exercise
- The plasma FFA concentration decreases during heavy exercise even though the adipose cell is stimulated by a variety of hormones to increase triglyceride breakdown to FFA and glycerol. This may be due to:
(a) the higher H+ concentration, which may inhibit hormone sensitive lipase
(b) the high levels of lactate during heavy exercise promoting the re-synthesis of triglycerides
(c) an inadequate blood flow to adipose tissue
