energy systems and bioenergetics

Energy Systems and Bioenergetics

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Energy systems and bioenergetics Skeletal muscles, especially in elite athletes, can

generate incredible work, during a marathon: Expend ~3000 Kcal, Oxidize >700 g CHO and >30 g fat Utilize >600 L oxygen, Break down and reform >150

mol ATP (63 kg) [ATP] in muscle very low Skeletal muscle can suddenly increase rate of ATP

use to > 100 times of rest Myosin-actin cross-bridge ~1/3 ATP hydrolyzed in contracting muscle is used in

Ca2+ uptake by SERCA (sarcoplasmic-endoplasmic reticulum calcium ATPase)

<10% ATP hydrolyzed by Na+-K+-ATPase

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Overview of muscle contraction

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ATP utilization during exercise

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Myosin and muscle contraction

Myosin consists of 6 polypeptide chains 2 myosin heavy chains (MHC), tail and head,

form cross bridges with actin 2 regulatory light chains, can be phosphorylated

by accepting a Pi from ATP 2 essential light chains

Myosin head also act as enzyme to hydrolyze ATP Myosin ATPase

ATP + H2O ADP + Pi

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Thick and thin filaments

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Myosin ATPase By itself, myosin ATPase activity low, but

increased by ~100 X when binds to actin Actin-activated myosin ATPase, actomyosin ATPase

Different kinds of skeletal muscle MHC Different ATPase activity, different rate of ATP

hydrolysis, myosin isoenzymes (myosin isoforms, different molecular forms of same enzyme, catalyzed same reaction with different speed)

Human: MHC I, IIA, IIX Smaller animals also have MHC IIB Fast- and slow-twitch fibers Muscle fibers have many nuclei, each express MHC

genes: single muscle fiber may have >2 different MHCs

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Histochemical Staining of Fiber Type

Type IIa

Type IIb

Type I

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Energy-rich phosphates ATP regeneration: ADP + Pi ATP + H2O Nucleotide: base + ribose + phosphate(s) ATP: energy-rich compound

Anhydride bonds between alpha and beta phosphates, and beta and gamma phosphates

Analogy of a spring In cell, [ATP]/[ADP] very high, ~500

Ensure ATP hydrolysis Muscle ATP utilization rate = regeneration rate in most

exercise situations Muscle [ATP] could decrease by 60-80% in very severe

exercise, but very short-lived, replenished very rapidly soon after exercise

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ATP structure

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Nucleosides

Nucleoside:Nucleoside: a compound that consists of D-ribose or 2-deoxy-D-ribose bonded to a nucleobase by a -N-glycosidic bond

anomericcarbon

a -N-glycosidicbond

HH

HH

OHOCH2

HO OH

O

O

HN

N

Uridine

-D-riboside

uracil

1'

2'3'

4'

5'

1

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Nucleotide

NucleotideNucleotide:: a nucleoside in which a molecule of phosphoric acid is esterified with an -OH of the monosaccharide, most commonly either the 3’-OH or the 5’-OH

5'

O-

O

O

H

H

OH

H

HOH

1'

-O-P-O-CH2

N

N N

N

NH2

3'

Adenosine 5'-monophosphate(5'-AMP)

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Phosphocreatine, creatine phosphate

[ATP] in most tissues low 3-8 mmol/L cell water, 2-6 mmol/kg tissue

Energy turnover rate in muscle 1 mmol ATP/kg/min at rest 240 mmol/kg/min in sprinting in elite athletes, ~

180 mmol/kg/min in normally active subjects ATP in muscle consumed in ~ 2s if not

regenerated ATP regeneration rate < maximal ATP

hydrolyzed rate Sprint speed at maximal at start

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Phosphocreatine ADP + PCr + H+ < ATP + Cr

Catalyzed by creatine kinase (very rich in muscle), fastest and most abundant among all muscle enzymes

Ensure ATP regeneration = break down near beginning of sprint-type activities

Act as temporary ATP buffer until other ATP-regenerating processes reach max rates

Forward direction in exercise, also consume H+ Backward direction in recovery

[PCr] in muscle 18-20 mmol/kg 92-96% PCr in human skeletal muscles

CK: MB isoenzyme in cardiac muscle, MM isoenzyme in skeletal muscle

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Energy systems

MgATP2- + H2O MgADP- + n H2PO4- + (1-n) HPO4 2- + (1-n) H+ All cellular ATP in cells associated to Mg2+

ATP regeneration PCr Oxidative phosphorylation Glycolysis Only glycolysis in red blood cell (erythrocyte)

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Energy systems

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Oxidative phosphorylation Aerobic system, aerobic metabolism, cellular

respiration, respiration Electrons transferred from substrate (CHO, fat)

carrier (NAD+, FAD+) O2 Measure disappearance of O2 as rate of oxidative

phosphorylation O2 consumption 1 L/min ~ 5 kcal/min

Can not quickly reach max rate because O2 transfer require time Require 15-20s to double the rate

High capacity: large fuel tank

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Oxidative phosphorylation

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Glycolysis Glucose + 2 ADP + 2 Pi + 2 NAD+ 2

pyruvate + 2 ATP + 2 NADH + 2 H+ Anaerobic glycolysis

Pyruvate + NADH + H+ < lactate + NAD+ Catalyzed by lactate dehydrogenase (LDH)

Pyruvate can enter TCA cycle Aerobic glycolysis

Net production of ATP from PCr and glycolysis: substrate-level phosphorylation

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Glycolysis and lactate Glycolysis has higher activities than oxidative

phosphorylation Generate more pyruvate than TCA cycle can oxidize Pyruvate converted to lactate, also regenerate NAD+

Capacity of generating ATP: PCr < glycolysis < oxidative phosphorylation

↓pH in very rapid rates of anaerobic glycolysis Glycolysis can be quickly started at beginning

exercise, reach max rate in 5-10 sec in intensive exercise

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PCr system, Anaerobic alactic system

ADP + PCr + H+ > ATP + Cr Consumption of H+ can be beneficial to muscle during

high-intensity exercise CK activity so high, can maintain ATP level remarkable

well even during intense exercise Low capacity: limited supply of PCr

[PCr] in muscle 18-20 mmol/kg, or 23-26 mmol/L [PCr] can decrease >90% in all-out exercise

Regeneration of PCr during recovery by oxidative phosphorylation

Half-time for PCr recovery ~ 30 sec Persons with higher capacity for oxidative ATP

formation recovery PCr at faster rate [PCr] and [TCr] Type II muscle fiber > Type I

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PCr recovery after exercise

Ex biochem c4-energetics 31Excess postexercise oxygen consumption (EPOC)

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Creatine supplementation Increase [Cr], [PCr], [Total Cr] PCr/TCr ratio in rested muscle constant at 0.6-0.7,

even after supplementation Most effective in short-term high-intensity exercise

lasting up to 3 min in duration Especially helpful if high-intensity activity is

repeated with only brief recovery period Increase body weight and strength gains along with

resistance training Allow to train harder Upregulate expression of some genes in muscles,

especially involved in intracullular signaling

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Ex biochem c4-energetics 35Energy sources in different exercise intensities

Ex biochem c4-energetics 36Energy sources in prolonged moderate-intensity exercise

Ex biochem c4-energetics 37Energy source during maximal exercise with different durations

Ex biochem c4-energetics 38Energy sources during repeated high-intensity exercise

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Adenylate kinase, AMP deaminase 2 ADP > ATP + AMP

Catalyzed by adenylate kinase (adenylyl kinase) Prevent [ADP] accumulation, maintain high [ATP]/[ADP], ensure

ATP hydrolysis AMP + H2O IMP + NH3

AMP deaminase (adenylate deaminase) NH4+ (ammonia) in blood

AMP deaminase activity higher in Type II fibers Low at rest, activated by↓pH, ↑[ADP]

The 2 reactions maintain optimal energy status in muscle fiber during intense exercise

Irreversible AMP deaminase reaction drives reversible adenylate kinase reaction to the right

During recovery, IMP converted back to AMP, or form inosine and hypoxanthine

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HN

NO

H

N

N

NH2

H

HN

N

H

CH3

Uracil (U)(in RNA)

Thymine (T)(DNA andsome RNA)

Cytosine (C)(DNA andsome RNA)

N

N

Pyrimidine

1

2

34

5

6

HN

N N

NO

HH2N

Guanine (G)(DNA and RNA)

N

N N

NNH2

HAdenine (A)

(DNA and RNA)

N

N N

N

HPurine

1

2

34

56 7

8

9

O O

O O

Inosine

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Purine nucleotide cycle

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Purine nucleotide cycle

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Plasma lactate and NH3 after intensive ex

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Muscle metabolism in exercise

Techniques to measure muscle metabolism Biopsy: invasive Phosphorus 31 (31P) nuclear magnetic

resonance (NMR) spectroscopy Magnetic resonance imaging (MRI) Identify ATP, PCr, Pi, estimate ADP, AMP Expensive, limited type of exercise

Ex biochem c4-energetics 49Identification of high-energy phosphate with 31P NMR

Jung & Dietze, 1999

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31P-NMR in PCr metabolism study

Slade JM, 2007

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Muscle ATP, PCr, LA in exercise

Ex biochem c4-energetics 53Epigenetics表觀遺傳學 , 擬遺傳學 , 後遺傳學 heritable change in gene expression in the absence

of changes to the sequence of the genome 沒有細胞核 DNA  序列改變的情況時， 基因功能的可逆的、可遺傳的改變

環境 , 飲食 , 運動 / 訓練… muscles cultured from endurance athletes had

significantly higher glucose uptake (a training-induced adaptation) than muscles cultured from untrained subjects (Berggren et a1. 2005).

Factors that regulate epigenetic regulation of muscle-gene expression can be affected by exercise training histone acetylation and methylation… Inheritable? unclear