Nutrition & Olympic biochemistry Flashcards
Compare and contrast type I AND type II muscle fibers in skeletal muscle
Which type of muscle fiber has higher energy demands? why? How does it mitigate high energy demands?
Describe muscular molecular machinery and the importance of ATP.
Type I fibres (slow oxidative):
-Slow, oxidative fibers
-rich in mitochondria and myoglobin
-red colour
-important for exercise requiring light activities and endurance (Ex: cycliists, long distance running)
-use variety of fuels (lactate, fat, ketones, AA)
Type II fibres:
- fast, anaerobic metabolism fibers.
-white colour
-important for short, high intensity activities
-fatigue easily
2 subtypes
-Type IIa: more mitochondria, more oxidative (fast oxidative)
-Type IIb: more glycolytic, more easily tired (fast glycolytic)
Type II fibres have a higher energy demand (produces ATP at a quicker rate)
-During vigorous activity, muscle must tap into other ATP sources than glucose (creatine, FA, lactate, ketones, AA)**
Molecular machinery:
ATP expenditure induces conformational change in myosin, causing locomotion of myosin and contraction.
What is the cori cycle? How is it an inter-organ pathway?
Is it fair to say that muscle makes use of glucose and fat to make energy?
Cori cyle: interorgan pathway between type II muscle fibers and the liver to return glucose to vigourously exercising muscle from its lactate byproduct.
- In muscle, glucose -> pyruvate through glycolysis (produces 2 ATP)
- In muscle, pyruvate -> lactacte
- Lactate travels in bloodstream to the liver
- In liver, lactate -> pyruvate
- In liver, pyruvate -> glucose through gluconeogenesis (uses 4 ATP and 2 GTP, from non-glucogenic sources)
- GLUT expels glucose (concentration gradient) and glucose travels in bloodstream to the muscle.
Yes, muscle uses both glucose and FA as energy sources. FA can enter the muscle and be beta-oxidized for energy.
What is ATP buffering (energy buffering)? What is the reaction?
Why does the muscle do this?
Where is creatine kinase found in muscle cells?
Is phosphocreatine found in fast or slow twitch muscle?
Energy buffering: storage of exess ATP as phosphocreatine (PCr) by transferring Pi on ATP to creatine (catalyzed by creatine kinase).
At rest, muscles still produce ATP, but it is not utilized. To “store ATP”, energy buffering is done. Muscle can tap into PCr storage when muscle glycogen is depleted.
Creatine kinase
-CKm: mitochondrial creatine kinase. Phosphorylates creatine with ATP output from mitochondria.
-CKc: cytoplasmic creatine kinase. Phosphorylates ADP from muscle use to ATP with phosphocreatine.
PCr is found in both muscles. But it’s more concentrated in fast-twitch muscle, for its high energy demands.
Which fuel is better for endurance events: carbohydrates or fat? Why?
What is carbo-loading?
Carbohydrates, such as glucose and glycogen are better, because they produce more ATP per mole of consumed O2 than fatty acids.
When oxygen rates are limiting, carbs are a better energy source, because they produce more ATP per mole of O2 utilized.
Carbo-loading: methods to increase muscle glycogen stores.
-Extends usage of glycogen during exercise event.
-Athletes do this because glycogen is a more efficient fuel than fat (ATP/O2 ratio)
-Compensated left ventricular hypertrophy: enlarged left ventricle muscle ensure efficient delivery of O2 to muscles.
What is the function of the PPP?
What are the 2 phases of PPP? Their functions?
Describe the 1st phase of PPP
Fct: produces NADPH (reducing power, protection agaisnt ROS), Ribose-5-Phosphate, and metabolic intermediates (F6P, G3P).
2 phases: oxidative phase (produce R5P, NAPDH), and non-oxidative/regenerative phase (produces cell signalling intermediates)
Oxidative phase:
G6P (from glycolysis) -> 3 reactions -> Ribulose-5-Phoshate
Through these reactions, 2 NADPH are produced from NADP+
G6PD catalyzes 1st reaction (NADPH), rate-limiting enzyme
6PGDH catalyzes 3rd reaction (NADPH)
Describe the general uses of the products of PPP
R5P: required for generation of ribose, which is a substrate for nucleotide production (DNA/RNA), cofactors and ATP.
NADPH: cofactor for lipogenesis and cholesterogenesis, protection agaisnt infection (produces ROS and oxidative burst in infection antigen containing phagosomes with NAPDH oxidase), antioxidant defense.
F6P, G3P: glycolysis/gluconeogenesis, metabolic intermediates
What is ROS?
How does ROS arise in a cell? How is it damaging?
How does the PPP provide antioxidant defense?
Describe the glutathione system
ROS: reactive oxygen species. Highly reactive electrophiles due to their unpaired electron. They are capable of accepting electrons from nucleophilic species (ex: biomolecules) causing oxidative damage and modifying structure/funcion of biomolecules.
ROS arise from mitochondria as a byproduct of oxidative phosphorylation in the ETC. Damaging to cells, can cause againg and metabolic disease
ROS is neutralized by 2 glutathione (GSH, small antioxidant) resulting in glutathione disulfide (GSSG, inactive glutathione).
To render glutathione active again, NAPDH provides reducing power and regenerates GSH.
Glutathione system:
GSH: 3 amino acids, glutamate, cysteine and glycine
2GSH (reduced) + H2O2 -> GSSG (oxidized) + H2O
by glutathione peroxidase (GPx)
GSSG (oxidized) + NADPH -> 2GSH (reduced) + NADP+
by glutathione reductase (GR)
How is ROS detected in a cell?
Describe the NRF2 system (in low ROS and high ROS levels)
Why are flavonoids beneficial?
How would cancer cell induced mutation of KEAP1, causing its inactivation, be beneficial to cancer cells?
Low ROS levels:
NRF2 (always expressed) binds to KEAP1 and is transported to 26S proteosome for degradation.
High ROS levels:
KEAP1 is oxidized by ROS agents, and degraded by the 26S proteosome.
NRF2 stabilizes and accumulates.
Binds to antioxidant gene in the nucleus, inducing transcription for NAPDH and GSH biosynthesis, GPx and GR, and antioxidants.
Flavonoids: produce electrophiles when metabolized, which interact with KEAP1, increasing ROS defense gene transcription.
Inactivation of KEAP1 would allow overexpression of NRF2, increasing ROS defense gene transcription. Chemotherapy increases ROS in cancer cells to trigger apoptosis. Increased ROS defense protects agaisnt this.
