October 18, 2023 Flashcards
Do practice questions at beginning of lecture
explain the process of glycogen metabolism starting with epinephrine binding to Beta-2 adrenergic receptor
Epinephrine Binding to Beta-2 Adrenergic Receptor:
Epinephrine, also known as adrenaline, is released in response to various stimuli, such as stress or exercise.
Epinephrine binds to the Beta-2 adrenergic receptor on the surface of target cells, including liver and muscle cells.
Activation of Adenylate Cyclase:
Binding of epinephrine to the Beta-2 adrenergic receptor activates an associated enzyme called adenylate cyclase.
Adenylate cyclase catalyzes the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP).
cAMP as a Second Messenger:
cAMP acts as a second messenger, relaying the signal from the cell surface to the intracellular components.
Increased cAMP levels activate protein kinase A (PKA), an enzyme involved in signal transduction.
Activation of PKA:
Activated PKA phosphorylates various target proteins, including those involved in glycogen metabolism.
In the context of glycogen metabolism, one key target of PKA is glycogen phosphorylase kinase (GPK).
Activation of Glycogen Phosphorylase Kinase (GPK):
Phosphorylation by PKA activates GPK.
Active GPK, then phosphorylates glycogen phosphorylase
Activation of Glycogen Phosphorylase:
Phosphorylation of glycogen phosphorylase by GPK (or PBK as referred to in lecture) converts it from the inactive “b” form to the active “a” form.
Active glycogen phosphorylase (OR PBK) catalyzes the breakdown of glycogen into glucose-1-phosphate (G-1-P).
Conversion of G-1-P to Glucose-6-Phosphate:
Glucose-1-phosphate (G-1-P) is further converted to glucose-6-phosphate (G-6-P) by the enzyme phosphoglucomutase.
what is calmodulin (CaM)
a calcium-binding protein
what does calmodulin (CaM) do in Glycogen metabolism
Activation of Phosphorylase Kinase:
When the intracellular calcium levels rise, as is the case during certain cellular signaling events, calmodulin binds to calcium ions, which causes conformational changes in calmodulin.
Calcium-bound calmodulin then activates phosphorylase kinase. Phosphorylase kinase is an enzyme that is crucial for the regulation of glycogen phosphorylase.
Phosphorylation of Glycogen Phosphorylase:
Active phosphorylase kinase, stimulated by calmodulin, phosphorylates glycogen phosphorylase.
This phosphorylation converts the inactive “b” form of glycogen phosphorylase into the active “a” form.
Activation of Glycogen Phosphorylase:
The conversion of glycogen phosphorylase from its “b” to “a” form allows it to catalyze the breakdown of glycogen into glucose-1-phosphate.
Active glycogen phosphorylase (OR PBK) catalyzes the breakdown of glycogen into glucose-1-phosphate (G-1-P).
Conversion of G-1-P to Glucose-6-Phosphate:
Glucose-1-phosphate (G-1-P) is further converted to glucose-6-phosphate (G-6-P) by the enzyme phosphoglucomutase.
What does the “slow” activation of Glycogen metabolism consist of
happens via epinephrine binding
What does the “fast” activation of Glycogen metabolism consist of
happens via calcium binding to calmodulin which activates GBK/PBK
what are beta blockers
Beta blockers, also known as beta-adrenergic blocking agents, are a class of medications that primarily target and block the effects of adrenaline (epinephrine) and related hormones on beta receptors in the body.
These medications are commonly prescribed to manage various medical conditions, primarily those related to the cardiovascular system
can people who are taking beta blockers still use glycogen as a energy source during exercise?
yes because we have another mechanism in place that is not dependent on Beta receptors via calcium binding to calmodulin
what is most likely a limiting factor during long-term exercise of two, three, 4 hours in length @30%-60% Vo2 Max
liver glycogen and blood glucose hypoglycemia
NOT MUSCLE GLUCOSE
Hypoglycemia is a medical condition characterized by abnormally low levels of blood sugar (glucose).
what is most likely a limiting factor during long-term exercise of two, three, 4 hours in length @70%-80% Vo2 Max
Muscle glycogen hypoglycemia
What exercise intensity is the most optimal for muscle to glycogen at a fast rate/great degree during long periods of time
70%-80%
at 70%-80% exercise intensity glycogen is a limiting factor
under conditions of 90%-120% Vo2 max is glycogen a limiting factor? Is your performance limited by glycogen
no, rather ACIDOSIS is the issue because you are exercising at intensities way above the lactate threshold, producing much more lactic acid
you’re going to be fatigued as a result of acidosis
How does training affect glycogen usage during long duration exercises
training enhances mitochondrial content
more mitochondrial content = more beta-oxidation enzymes
more beta-oxidation enzymes = greater reliance on fat metabolism and you’re going to spare/save carbohydrate usage
this is important because we have gram quantities of carbohydrates and kilogram quantities of fat
what is the difference between a trained and untrained person during long duration exercises
trained person is not using glycogen at the same rate because they are able to use fat more than carbohydrate
thus “sparing”/preserving limited stored glycogen and reducing glycogen usage
what is glycogen “sparing”
an adaptation that occurs in endurance trained individuals, due to greater use of lipid substrates –> delays glycogen depletion and fatigue during exercise
what is glycogen “loading”
glycogen loading increase the amount of glycogen available at the start of exercise —> delays glycogen depletion and fatigue during exercise
what are two methods marathon runners can adaopt to delay fatigue
glycogen “sparing” due to training
glycogen “loading”
which diets: Mixed, Protein + fats, or Carbohydrates, do you think will cause athletes to last longer during long exercises
Carbohydrates
describe the 3 procedures of Glycogen loading
procedure 1:
Mixed diet + High CHO diet
procedure 2:
Mixed diet + Exhaustive exercise + High CHO diet
procedure 3:
Mixed diet + Exhaustive exercise + fat and protein diet + High CHO diet
SEE PAGE GRAPHS ON BOTTOM OF PAGE 67 for EACH procedures effect on MUSCLE GLYCOGEN STORES
During fasting, or starvation or CHO deprivation, how are you going to maintain your blood glucose levels
gluconeogenesis
Gluconeogenesis is a metabolic process in which the body synthesizes glucose (a sugar) from non-carbohydrate precursors.
This process primarily occurs in the liver and it is essential for maintaining blood glucose levels when dietary sources of glucose are insufficient, such as during fasting or low-carbohydrate intake.
if you’re not taking in any carbohydrates then insulin levels will drop. true or false
true
because it is CHO and glucose in diet that stimulate beta cells to produce insulin
what is an anabolic hormone
Anabolic hormones are a group of hormones that promote growth, development, and the synthesis of complex molecules in the body.
is insulin an Anabolic hormone
yes
Insulin: While primarily known for its role in regulating blood sugar, insulin also has anabolic properties.
It helps promote the uptake of glucose and amino acids by cells, facilitating muscle protein synthesis and tissue growth.
During fasting, or starvation or CHO deprivation,insulin in the blood is reduced which leads to:
increased protein breakdown
increase lipolysis (fat breakdown)
increase alanine and glycerol in blood
increase gluconeogenesis in liver to prevent hypoglycemia
refer to page 68
insulin normally inhibits…
fat lipolysis
muscle protein degredation
liver and muscle glycogen breakdown
what is the role of HSL in lipolysis
Hormone-sensitive lipase (HSL) is an enzyme that plays a central role in the process of lipolysis, which is the breakdown of stored triglycerides (fat) into glycerol and free fatty acids for use as an energy source.
Activation:
activated when specific hormones bind to receptors on the surface of fat cells. These hormones include epinephrine (adrenaline), norepinephrine, glucagon, and adrenocorticotropic hormone (ACTH).
*also sensitive to PH
Breakdown of Triglycerides:
Once activated, HSL catalyzes the hydrolysis (breakdown) of triglycerides, which are the storage form of fat in adipocytes. Triglycerides consist of a glycerol molecule and three fatty acid molecules. HSL breaks the chemical bonds holding the fatty acids to the glycerol backbone.
Release of Glycerol and Free Fatty Acids:
The breakdown of triglycerides by HSL results in the release of glycerol and free fatty acids into the bloodstream. Glycerol can be used by various tissues, particularly the liver, to produce glucose through a process called gluconeogenesis. Free fatty acids can be taken up by muscle cells and other tissues for energy production.
Energy Utilization: Within cells, free fatty acids are transported into the mitochondria, the energy-producing organelles, where they undergo beta-oxidation. During beta-oxidation, fatty acids are broken down into acetyl-CoA, which enters the citric acid cycle (Krebs cycle) to generate ATP, the body’s primary energy currency.
is HSL also sensitive to PH
yes
PH changes as a result of exercise
explain citrate inhibition of PFK and its relation to why we start to use more fat and inhibit glucose oxidation during long duration exercise
citrate inhibition of PFK
Citrate Production: During prolonged exercise, the body’s energy demands increase, and the citric acid cycle (Krebs cycle) within the mitochondria becomes highly active to produce energy from various substrates, including glucose and fatty acids. The citric acid cycle generates citrate as an intermediate product.
Citrate Accumulation: As the citric acid cycle becomes more active, citrate accumulates within the mitochondria. Citrate can exit the mitochondria and enter the cytoplasm.
Citrate Inhibition of PFK: Citrate has an inhibitory effect on PFK, an enzyme in the glycolysis pathway that regulates the rate of glucose metabolism. Specifically, citrate acts as an allosteric inhibitor of PFK.
Inhibition of Glycolysis: When PFK is inhibited by citrate, the rate of glycolysis decreases. This means that less glucose is metabolized to produce pyruvate and, subsequently, less pyruvate is available to enter the mitochondria for further energy production.
Increased Reliance on Fat Oxidation: With reduced glycolysis and limited glucose metabolism, the body shifts its energy source toward fat oxidation. The breakdown of fatty acids in the mitochondria becomes more prominent, and more acetyl-CoA molecules are generated from the oxidation of fatty acids.
Sparing Glucose: This shift toward fat oxidation “saves” glucose for tissues that are highly dependent on glucose, such as the brain and red blood cells, by preventing its excessive utilization during long-duration exercise.
refer to page 69
