Energi Kontraksi Otot

dr. Susila Sastri M.BiomedBiokimia FK UNAND

ATP

• Energy for the contracting muscle cell : ATP• ATP conc. in muscle cells : 25 mmol/kg of dry

skeletal muscle tissue, • This amount is sufficient to keep muscles

contracting at their maximal capacity for only a few seconds, thus active muscle cells must be able to recycle ADP to ATP to maintain contraction.

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Structure of ATPadenosine triphosphate

Function of ATP

• The contractile process.• The pumping of calcium back into the

sarcoplasmic reticulum during relaxation.• Maintaining the sodium/potassium ion

gradients across the sarcolema (membrane potential).

Source of ATP

• Karbohidrat : Glycolisis, TCA• Fat : Oxidation, TCA• Protein : Deamination, TCA• The sarcoplasm of skeletal muscle : large stores

of glycogen, located in granules close to the I bands.

• The release of glucose from glycogen is dependent on a specific muscle glycogen phosphorylase , which can be activated by Ca2+, epinephrine, and AMP.

Creating an H+ Gradient

NADH

OUTER COMPARTMENT

INNER COMPARTMENT

Making ATP: Chemiosmotic Model

ATP

ADP+Pi

INNER COMPARTMENT

Pathways that provide for ATP synthesison aerobic conditions:

• Phosphocreatine.• Glycolysis from Glycogen or Glucose.• Tricarboxylic acid cycle (TCA or Krebs cycle).• Electron transport chain.

• If the need for contraction extends beyond a few seconds, fibres which require glucose as their fuel and energy source will begin to rely on hepatic gluconeogenesis to top-up their fuel supply and oxidative-type muscle fibres will increase their use of fatty acid to produce acetyl-coenzyme A for the TCA cycle.

• myocytes have enzyme-driven mechanisms which efficiently recycle ADP generated during contraction.

• A key enzyme in the process of recycling lactate from muscle to liver is lactate dehydrogenase (LD) which catalyses the reversible interconversion of lactate and pyruvate.

• LD occurs in five isoenzymic forms and is widespread in cells around the body. The five isoenzymes arise due to the quaternary arrangement of the four subunits which comprise the enzyme. The subunits are of two types, H (heart) and M (muscle)

Lactate dehydrogenase (LD)

Isoenzymic forms of lactate dehydrogenase

A. Energy metabolism in muscle fibers

• Red fibers (type I fibers): prolonged effort. Their metabolism is mainly aerobic and therefore depends on an adequate supply of O2.

• White fibers (type II fibers: fast, strong contractions. These fibers are able to form sufficient ATP even when there is little O2 available, mainly obtain ATP from anaerobic glycolysis

• Red fibers provide for their ATP :– fatty acids: β-oxidation– tricarboxylic acid cycle– respiratory chain

• The red color : monomeric heme protein myoglobin, which they use as an O2 reserve.

• Myoglobin: higher affinity for O2 than hemoglobin and therefore only releases its O2 when there is a severe drop in O2 partial pressure

Regeneration of ATP• Two enzymes, creatine kinase (CK) and adenylate

kinase (AK), are important in this context:• Creatine and creatine kinase: Creatine is

synthesized from glycine and arginine and requires S-adenosyl methionine (SAM) as a methyl group donor.

• Creatine phosphate (also called phosphocreatine, PCr)– a small compound which is a more ‘energy rich’– able to rephosphorylate ADP so acts as an ‘energy

buffer’

Phosphocreatine(creatine phosphate / Pcr)

• Energy stored in the skeletal muscle.• Creatine : synthesized in the liver (from Arg,

Gly, Met), and transported to the muscle cells, where it is phosphorylated by creatine kinase (ATP is required) to creatine phosphate.

• Serve as an ATP buffer in muscle metabolism.

Creatine synthesis

Creatine Kinase (CK)

• The enzyme responsible for this ‘topping-up’ ATP in active muscle is CK.

• CK is found in high concentration in muscle cells

• isoenzyme : CK-MM, CK-BB and CK-MB. • predominant form in all muscles : CK-MM, but

cardiac muscle also contains a significant amount of CK-MB and this isoenzyme can be used as a specific marker of myocardial

Adenylate kinase (AK)

• Whereas CK rephosphorylates ADP using PCr as the phosphate donor, AK (myokinase / AMP kinase)

Fatty acid as a fuel in muscle

• Fatty acid oxidation occurs in mitochondria and peroxisomes in most tissues but quantitatively muscle is a major consumer of fat.

• fatty acids : more calorific : 38 kJ/mol, compared with 16 kJ/mol for glucose.

Proteins and amino acids as fuels

• amino acids may be used as fuels : during times when carbohydrate metabolism is compromised, for example, starvation or prolonged vigorous exercise.

• several different amino acids into intermediates of glycolysis (e.g. pyruvate) or the TCA cycle (e.g. oxaloacetate).

• Alanine released from muscle protein or which has been synthesized from pyruvate via transamination, passes into the blood stream and is delivered to the liver.

• Transamination in the liver converts alanine back into pyruvate which is in turn used to synthesise glucose; the glucose is exported to tissues via the blood. This is the glucose-alanine cycle

Glucose-Alanin Cycle

Recycling of ADP

• Muscle contraction produces ADP; if this cannot be recycled to ATP contraction will cease.

• Rephosphorylation of ADP by mitochondrial oxidative phosphorylation is an obvious option for regenerating ATP, but this applies mainly to oxidative type I fibres.

The multiple sources of ATP in muscle.

• Sprinter: Creatine Phosphate & Anaerobic Glycolysis to make ATP. –100-m sprint : creatine phosphate (first 4–5

seconds) and then anaerobic glycolysis, using muscle glycogen as the source of glucose.

• Marathon Runner Uses Oxidative Phosphorylation–The major fuel sources are blood glucose

and free fatty acids, largely derived from the breakdown of triacylglycerols in adipose tissue, stimulated by epinephrine.