Final Exam L21

Muscle and Metabolism

Muscle types

• Skeletal (main focus of this lecture)
• Cardiac
• Smooth

Skeletal muscle terminology

1. Muscle cell, also known as muscle fiber, myocyte
• Multi-nucleated and cannot divide
• Contain bundles of regularly arranged filaments
called myofibrils
2. Sarcolemma = plasma membrane
3. Sarcoplasmic reticulum = specialized smooth ER
which stores calcium important for contraction
4. Sarcomere = functional contractile unit

Aerobic vs anaerobic metabolism

Aerobic metabolism uses oxygen and mitochondria, aided by muscle myoglobin, while anaerobic metabolism relies on glucose without oxygen; slow-twitch fibers are more aerobic (more mitochondria, less glycogen) and fast-twitch fibers more anaerobic (less mitochondria, more glycogen).

Markers of skeletal muscle damage

• AST (aspartate aminotransferase)
• CK (creatine kinase)
• LDH (lactate dehydrogenase)
• ALT (alanine aminotransferase) – when high levels of damage are present

Resting Muscle Metabolism and the Starve-Feed Cycle

Hormonal regulation: insulin

• Insulin stimulates transport of nutrients and glucose into muscle
• Glucose enters by GLUT4 moving to the plasma membrane (as a result of insulin signaling)
• Amino acids are transported into muscle
Insulin signaling leads to activation of phosphatase enzymes that either turn on or turn off key
metabolic processes related to these functions

Resting Muscle Metabolism and the Starve-Feed Cycle

Carbohydrate metabolism

• Increased glucose uptake through insulin/GLUT4
Increased glycolysis/ATP production
• Glucose also used to replenish muscle glycogen stores

Resting Muscle Metabolism and the Starve-Feed Cycle

Fatty acid metabolism

Insulin increases lipoprotein lipase in muscle capillaries, releasing fatty acids from chylomicrons/VLDL for ATP production or muscle maintenance.

Resting Muscle Metabolism and the Starve-Feed Cycle

Amino acid metabolism

Dietary amino acids are taken up by muscle and used for protein synthesis

Resting Muscle Metabolism and the Starve-Feed Cycle

Overall fuel utilization in muscle under resting conditions:

Skeletal and cardiac muscle vary in their use of metabolic fuel
• Well-fed resting skeletal muscle oxidizes approximately 50% glucose/50% fatty acids
• Well-fed cardiac muscle oxidizes a high level of fatty acids (in addition to glucose) due to
its high aerobic requirements (always working).

Resting skeletal muscle in the starved state

Hormonal regulation

Hormonal regulation:
Insulin levels decrease

Counter-regulatory hormones increase
• Glucagon
• Epinephrine
• Cortisol

Resting skeletal muscle in the starved state

Carbohydrate metabolism

• Reduced glucose uptake from blood due to low insulin/GLUT4 transport, spares glucose
for vital organs.
• Muscle glycogen will be degraded to generate glucose. This supports glycolysis and
generation of ATP in muscle, but will only last approximately 24 hours

Resting skeletal muscle in the starved state

Fatty acid and ketone body metabolism

• During the first 2 weeks of starvation, muscle uses fatty acids from adipose tissue and
ketone bodies from the liver.
• After about 3 weeks of starvation, muscle uses predominantly fatty acids – spares
ketone bodies for brain

Resting skeletal muscle in the starved state

Amino acid metabolism

Early in starvation, muscle catabolism releases mostly glutamine and alanine (very high) (~50–60%) because they carry nitrogen for urea formation, serve as primary gluconeogenic substrates, and support GI, kidney, and immune functions, though muscle loss continues over time.

Metabolism of the Brain

Key features of brain/blood brain barrier

The nervous system has neurons and glial cells; neurons have limited (pretty much no) regeneration, and the blood-brain barrier—formed by endothelial cells, astrocytes, and pericytes—controls brain entry of molecules using specialized transporters and ATP from mitochondria.

Metabolism of brain in the well-fed state

The brain relies mainly on glucose for energy (insulin-independent), requires amino acids for neurotransmitter synthesis and normal turnover/protein maintenance, and uses very little fatty acids, though ketone bodies can be utilized during starvation or ketogenic diets.

Metabolism of the brain during starvation

During starvation, the brain remains glucose-dependent but increasingly uses ketone bodies after ~3 weeks to spare muscle; it is highly aerobic, making it extremely sensitive to oxygen deprivation, as in ischemic stroke.

Aerobic versus anaerobic metabolism in the brain

The brain is extremely oxygen-dependent, becoming unconscious within 5–10 seconds of oxygen loss, unlike other tissues that can survive ~30 minutes without oxygen.

Ischemic stroke

Ischemic stroke: due to closure/blockage of a blood vessel. Reduced blood supply
deprives tissue of not only oxygen, but also glucose and prevents removal of waste.
Potential causes: blood clots, plaque accumulation in arteries

Hemorrhagic stroke

Hemorrhagic stroke: due to bleeding from a blood vessel, loss of blood reduces flow to
location of affected artery.
Potential causes: blood vessel abnormalities/malformations, hypertension, head
injuries, brain tumors, drugs, aneurysm