Biochemistry of Muscle Contraction

Biochemistry of Muscle Contraction

Fred P. Guillergan M.D., FPCP

Outline


histology and biochemistry of muscles (Striated & smooth) – Myosin – Actin, Tropomyosin, Troponin – Accessory proteins of muscles Biochemical events in muscle contraction Calcium, Ca2+-binding proteins and Ca2+ channels in muscle contraction Biochemistry of Cardiac & Smooth muscle contraction Energetics of muscle contraction

☻Able to understand the normal anatomy and physiology of different types of muscles ☻ Provide knowledge of the metabolic processes in muscles ☻ Provide bases for understanding how muscles react to certain drugs or foreign substances ☻ Able to understand diseases of the muscles

Biomedical Importance of the Biochemistry & Molecular Biology of Muscle

Three Types of Muscles
☻Skeletal muscle ☻Cardiac muscle ☻Smooth muscle

Skeletal muscle fiber

• Many myofibrils Embedded in sarcoplasm • Enclosed by sarcolemma: electrically excitable membrane
• Supplied by energy compounds (ATP, phosphocreatine) & Glycolytic enzymes • Multinucleated with many mitochondira • Intimately associated with T tubules and SR

View from an electron microscope

actin

myosin

Thick filaments
-55% of protein by wt.
Papain - assymetric hexamer - mol. Mass of 460 kDa - has actin binding site Light chains - has ATP binding site w/ ATPase activity

Trypsin
Heavy chains

Thin filaments (G-actin)
- monomeric (G) actin - 25% of muscle protein by wt. - polymerizes at physiologic ionic strength with Mg2+

F-actin
-6-7 nm thick

- pitch every 35.5 nm

Tropomyosin & Troponins

Tropomyosin – fibrous molecule, a dimer (ά and β) attach to F-actin
Troponin – TpT (binds to tropomyosin and the other troponins)

– TpI (inhibits the F-actin-myosin interaction)
– TpC (calcium binding polypeptide)

Accessory Proteins in muscles


* Titin  – largest protein known (human heart isoform has 27,000 amino acids)
– Filamentous protein that reaches from the