Chapter 3- Fuel for Muscle and Exercise Metabolism Flashcards
what provides energy for muscle contraction?
the breakdown of ATP into inorganic phosphate and ADP
what are type I fibers ?
slow-acting, more myoglobin therefore more capacity for oxidative metabolism
what are type II fibers
fast-acting, fewer mitochondria and capillary supply, fatigue rapidly
what are the three things contained in skeletal muscle
75% water
20% protein (myosin, actin, tropomyosin)
5% salts and substances
the hydrolysis of ATP yields how many kJ? kcal ?
31 kJ or 7 kcal
what is the formula of ATP hydrolysis ?
ATP + H2O=> ADP+ Pi + H+
what are the three mechanisms involved in resynthesis of ATP
PCr hydrolysis
glycolysis
TCA cycle
what is the resting concentration of ATP in muscle? what does this imply
4-5 mmol/kg ww muscle (only enough energy for a few seconds)
when does PCr hydrolysis begin ? what is its purpose
at immediate onset of contraction to buffer ADP accumulation after you use up the initial quantity of ATP in muscle. this prevents rapid acidification of the muscle and therefore premature fatigue
how much is [PCr] in sarcoplasm compared to ATP
3-4x
why can’t we rely only on PCr hydrolysis ?
rate of PCr hydrolysis declines after only a few seconds of maximal force contraction
where does PCr hydrolysis occur
the sarcoplasm
how does glucose uptake from blood happen? with help from what ?
GLUT4 transporter
what occurs to prevent the loss of glucose from the cell after it passes through the transporter in the muscle ?
an irreversible phosphorylation catalyzed by hexokinase.
glucose + ATP => ADP+ glucose-6-phosphate
why is the transformation of glucose into glucose-6-phosphate irreversible in the muscle and not the liver?
because skeletal muscles lack the enzyme glucose-6-phosphatase, but the liver does not
how does one control the production of glucose-6-phosphate in the skeletal muscle ?
by negative feedback on hexokinase
how does one break down muscle glycogen in order to utilize it ? (formula)
glycogen phosphorylase breaks off glucose molecule from glycogen
glycogen + Pi => glucose-1-phosphate + glycogen shorter by one glucose
then, glucose-1-phosphate has the Pi placed on a different carbon to become glucose-6-phosphate with phosphoglucomutase
what is the amount of ATP used in glycogen breakdown ?
none
you use an inorganic phosphate to bind to glucose so no ATP needed
what does phosphoglucomutase do
in glycogen breakdown, glucose-1-phosphate has the Pi placed on a different carbon to become glucose-6-phosphate
what are the two sources for glycolysis
glucose and glycogen
what is the main step between glucose/glycogen and pyruvate in glycolysis ?
fructose-1,6-bisphosphate is cleaved by aldolase into 2 glyceraldehyde-3-phosphate
when pyruvate is produced, what are the two pathways for it ?
either it becomes lactate or acetyl CoA
how does pyruvate become lactate
with lactate dehydrogenase
pyruvate+ NADH => lactate+ NAD+
how does pyruvate become acetyl coA
with pyruvate dehydrogenase
pyruvate+ CoA + NAD+ => Acetyl CoA + NADH
in glycolysis from glucose, what is the total ATP produced ? the net ATP produced ?
total ATP = 4 (2 from each glyceraldehyde-3-phosphate)
net = 4-2 = 2
in glycolysis from glycogen, what is the total ATP produced ? the net ATP produced ?
total ATP = 4
net= 4-1 = 3
what happens if glycolysis is too fast?
availability of NAD+ (necessary cofactor) becomes the limiting factor, and the reaction is limited at the 2 3C chain split (stays at glyceraldehyde 3-phosphate)
how can one regenerate the NAD+ in muscle ?
reduction of pyruvate to lactate
when does lactate formation occur ?
always, it’s just that it accumulates in heavy exercise
how does the body deal with lactic acid accumulation ?
lactate brought to liver and converted back to glucose in the Cori Cycle
what does the Cori Cycle do
lactate brought to liver and converted back to glucose
what is the main goal of the Cori Cycle
gluconeogenesis
in resting state, how many ATP and lactate are needed in the Cori Cycle to produce 1 glucose ?
2 lactate and 6 ATP
where is the Cori Cycle taking place ? why
the liver because lactate can only go to pyruvate and therefore glucose in the liver
what does TCA cycle stand for
tricarboxylic acid cycle (Krebs)
what are the two main sources of energy for the TCA cycle
fats and carbs
where does the TCA cycle occur ?
in the mitochondrion
where does glycolysis occur ?
cytoplasm/sarcoplasm
how does a pyruvate get into the TCA cycle ?
it has to first go to the mitochondrion from the cytoplasm
what are the two nutrients needed in enzymatic reactions ?
NADH and FADH2
what and where is the electron transport chain
creates a proton gradient across inner membrane and mitochondrial matrix
what does oxygen do in the ETC
removes electrons from the chain
how much ATP is made from ETC ?
38 ATP
after how long is glycogen depleted in exercise ?
1-2 h
what determines the sustainability of an exercise ?
glycogen stores
what is the enzyme responsible for lipolysis
?
hormone-sensitive lipase
what are the 5 hormones that stimulate HSL ?
epinephrine norepinephrine glucagon cortisol growth hormone
what inhibits HSL ?
insulin
what does HSL do ?
breaks down triacylglycerol into glycerol and 3 FA which go into the blood
break down the source of the 38 ATP from the complete oxidation of one glucose molecule
from glycolysis:
2 + 6 (from NADH)
from TCA:
24 (from NADH) + 4 (from FADH2) + 2 (from GTP)
therefore 38 in total
how do fatty acids enter the mitochondria ?
< or = to 12 carbons without membrane transporter
> or = to 14 carbons with membrane transporter
why does insulin inhibit HSL ?
bc it promotes TG synthesis
during prolonged moderate exercise, what is the rate of lipolysis and the rate of entry of FA into circulation like ?
adipose tissue blood flow increases
during intense exercise, what is the rate of lipolysis and the rate of entry of FA into circulation like ?
SNS vasoconstriction causes fall in adipose tissue blood flow, meaning accumulation of FA in adipose tissue
the concentration of what limits fat mobilization during intense exercise
lactate because a high amount promotes re-esterification (more TG) and therefore limits entry of FA into bloodstream
what happens to glycerol once it’s in the circulation ?
taken up by liver or converted into glucose
what happens to FA once they are in circulation ?
loosely bounded with albumin for the most part
what is uptake of FA by muscle related to directly ?
the plasma FA concentration
how do long chain (= or > 14 carbon) FFA get into the mitochondria for oxidation ?
via the carnitine shuttle
what is the carnitine shuttle ?
two forms of carnitine-acyl-transferase in the mitochondrial membrane of the muscle. CAT-I outside membrane, CAT-II on inner surface.
FFA becomes FA-CoA or acyl-CoA with acyl-CoA synthetase
then, at the outer membrane, acyl-CoA releases its CoA and binds to carnitine (fatty acyl-carnitine + free CoA) which transports it across membrane in carnitine transporter.. then in the mitochondrion, carnitine is removed and fatty acyl-CoA is reformed
what is the main rate-limiting step in utilization of FFA for energy ?
carnitine shuttle
beta-oxidation cleaves how many carbons at a time? what does this imply for the beta oxidation of a 16 carbon FA ?
2 carbons at a time
for a 16C- cleave 7 times
what is CAT I (carnitine acyl-transferase) inhibited by ?
malonyl CoA
what does malonyl CoA do ?
promote TG formation in cell and therefore inhibits CAT I
what does beta-oxidation achieve ?
breakdown of carbons in order to create acetyl CoA to be used in TCA
what are ketones ?
by-products of incomplete fat catabolism
what are 3 examples of ketones ?
acetone
acetoacetate
beta or 3-hydroxybutyrate
what do ketones consist of
2 acetyl CoA form acetoacetate which then can transform reversibly or irreversibly into other ketones
what ketone reaction is irreversible
acetoacetate to acetone
what is ketosis ?
elevated concentration of ketone bodies (>3mg/dL)
what is ketoacidosis ?
concentration of ketones > 90 mg/dL
overwhelms normal compensatory mechanisms
in a type I diabetic, what will be the concentration of ketones ?
90 mg/dL
in a healthy person, what will be the concentration of ketones ?
<3 mg/dL
when would a ketogenic diet be suggested ?
pediatric epilepsy
what 2 normal compensatory mechanisms do we have for ketosis ?
bicarbonate buffering
and respiratory compensation
usually, proteins contribute to how much of energy provision ?
5%
when do proteins contribute more to energy ?
starvation or depletion of glycogen stores
what are the two things that happen before a protein can be oxidized ?
transamination (removal of NH2 group, transfer it to a ketoacid to form a different amino acid)
deamination (formation of ammonia)
remaining molecule can enter TCA
how many amino acids can be oxidized to significant amounts ?
6
what are the 6 amino acids that can be oxidized to significant amounts ?
leucine isoleucine valine asparagine aspartate glutamate
how is energy extracted from protein amino acids ?
after it is digested and absorbed into liver, it can be synthesized into proteins or released into blood for cellular uptake
if there is excess protein consumption, what happens ?
used for energy, and the extra is converted into fatty acids for storage as TG
why is it untrue that more protein= more muscle ?
because extra protein will turn into TG in storage
what are the two kinds of amino acids in terms of structure ?
glucogenic and ketogenic
give 5 examples of glucogenic a.a
alanine glycine serine cysteine tryptophan
give 2 examples of ketogenic a.a
lysine, leucine
what happens to the carbon skeletons of glucogenic a.a ?
turn into pyruvate, which will then either go to gluconeogenesis in the liver or become acetyl coA and to into TCA
what happens to the carbon skeletons of ketogenic a.a ?
turn into acetyl coA and then either become FFA, ketones, or go into TCA
in the process of deamination in the liver, what happens to the NH3 (ammonia) ?
becomes urea and excreted by kidneys in urine
what is gluconeogenesis ?
formation of glucose from non carb sources such as protein
how do CHO intake impact protein metabolism
low CHO = high protein metabolism
at 60% VO2max what is one’s main source of energy at the onset of workout ?
ATP and PCr
at 60% VO2max what is one’s main source of energy at 5-10 s of workout ?
glycolysis
at 60% VO2max what is one’s main source of energy after a few minutes ?
glycogen stores
at 60% VO2max what is one’s main source of energy at 30 min ?
glycogen but starting to metabolize fat
at 60% VO2max what is one’s main source of energy at 45 min ?
glycogen and fat
how much glycogen is stored in liver and muscle and blood
liver: 100g
muscle: 300g
blood: 0.9g/L or 5 mmol/L
where is fat stored ?
in white adipose tissue and also intramuscularly
where is fat found in muscle ?
dispersed along muscle fibers, close to mitochondria within fibers
what supports the view that intramuscular fat could be a good source of energy during prolonged exercise ?
decrease of intramuscular triglyceride post-exercise
which fibers contain more intramuscular triglyceride ?
type I
which nutrient is the best at energy storage ?
fat
what is the drawback to fat as fuel ?
slow, takes more time to tap into it as source of fuel
1g fat, carb, protein= ? kcal
1 g fat= 9 kcal
1 g carb = 4 kcal
1 g protein = 4 kcal
why are carbs not as efficient in storage ?
1g carb stored with 3g water, less efficient and can be overloaded with water
how much exercise time can blood, muscle, and liver CHO provide ?
2 hrs
how much exercise time can fat provide ?
> 80 hrs but you need to know how to utilize it
how much exercise time can protein provide ?
30 hours but rarely used (only in dire situations)
what is the limitation to fat as fuel in high intensity exercise ?
can’t maintain exercise at an intensity higher than 60% VO2max
what are 4 intramuscular factors that regulate mobilization of fuels
ATP/ADP
Pi
AMP
Ca2+
how does ATP regulate fuel mobilization
decline in ATP cellular concentration means parallel increases in ADP and AMP, directly stimulate anaerobic and oxidative resynthesis
what is the rate-limiting step in glycolysis ?
conversion of fructose-6-phosphate to fructose-1,6-diphosphate by phosphofructokinase (PFK)
what is the rate-limiting step in glycogen breakdown to prepare for glycolysis ?
glycogen phosphorylase concentration who converts glycogen to glucose-1-phosphate
what is the rate-limiting step in carb oxidation
from pyruvate to acetyl coA by pyruvate dehydrogenase
what is the rate limiting step in the TCA cycle ?
citrate synthase concentration
what controls glycogen phosphorylase in the rate-limiting step of glycogen breakdown
glycogen breaking down to glucose-1-phosphate
+ AMP, Pi, Ca2+, epinephrine
- ATP
what controls phosphofructokinase in the rate-limiting step of glycolysis
fructose-6-phosphate going to fructose-1,6-diphosphate
+ ADP, AMP, Pi, NH4+
- ATP, H+
what controls pyruvate dehydrogenase in rate limiting step of carb oxydation
pyruvate goes to acetyl coa
+ Ca2+, ADP, CoA, NAD+
- ATP, NADH
what controls citrate synthase in rate limiting step of TCA ?
+ ADP, NAD+
- ATP, NADH
which hormone is anabolic ?
insulin
which hormones are catabolic ?
all those we’ve learned except insulin
glucagon: how is it stimulated and what does it do
stimulated by fall in blood glucose
stimulates gluconeogenesis and liver glycogen breakdown
epinephrine: how is it stimulated and what does it do
stimulated by stress and fall in blood glucose
stimulates glycogen breakdown and lipolysis
norepinephrine: how is it stimulated and what does it do
stimulated by stress, fall in blood glucose and BP
stimulates glycogen breakdown and lipolysis
cortisol: how is it stimulated and what does it do
stimulated by stress, ACTH, interleukin-6
stimulates protein breakdown, lipolysis, gluconeogenesis
growth hormone: how is it stimulated and what does it do
stimulated by stress
stimulates lipolysis
interleukin-6: how is it stimulated and what does it do
stimulated by Ca2+ and decreased glycogen
stimulates glycogen breakdown, cortisol secretion, lipolysis
insulin : how is it stimulated and what does it do
stimulated by rise in blood glucose and amino acid
stimulates uptake of blood glucose and amino acids
inhibits lipolysis and protein breakdown
why does Ca2+ cause positive feedback for energy ?
stimulates GLUT4 translocation and therefore glucose uptake
in exercise, what is enhanced in order for cells to take in glucose ?
GLUT4
how is insulin enhanced in exercise ?
it’s not
what promotes GLUT4 translocation
Ca2+ increase due to exercise
what mostly promotes GLUT4 at rest ? in exercise
at rest: insulin
in exercise : Ca2+
how does epinephrine and glucagon act upon a cell to activate HSL ?
bind to membrane, release adenylate cyclase and enzyme cascade, covalent activation leads to hormone activation
what role does cortisol have in lipolysis ?
increases effectiveness of catecholamines
if you stop exercising, does lipolysis stop right away
no
what is fatigue ?
inability to maintain work at a given force/power output
what will the rates of anaerobic ATP resynthesis be like from PCr hydrolysis over time ?
at first, strong
then, declines abruptly until there is almost none at 20-30s
what will the rates of anaerobic ATP resynthesis be like from glycolysis over time ?
slowly increase until a drop at 20-30s
in a graph with x=time and y=g glycogen/kg muscle, how will the slope vary with varying %VO2max
at 120%VO2max, extremely sharp drop in slope
then less and less sharp drop
30% VO2max depletion much slower, since there is also fat oxidation that supplies energy
in a graph with x=time and y=g glycogen/kg muscle, what are the two things we can look at with varying %VO2max
the slope of decline in glycogen and also the duration of the exercise
30%Vo2max able to last longer and with less of a decline in glycogen bc there is also fat utilization
why is there a drop in plasma FA at 30 min of exercise ?
fatty acid oxidation takes time, usually starts at 30 min after prolonged exercise, therefore will use up plasma FA until lipolysis comes through at 30 min
when does peak uptake of glucose occur regardless of exercise intensity ?
90 min
how can one increase the utilization of glucose depending on the intensity of the workout ?
increase intensity and you’ll uptake more glucose
as duration of exercise increases, which fuel utilization will increase the most ?
fat
as duration of exercise increases, which fuel utilization will decrease the most ?
muscle glycogen
what is a way of replenishing glycogen stores ?
sports drinks
in resting post-absorptive state, glucose release is enough only for what ?
CHO demands of CNS
energy going to CNS in post absorptive state is what%
70% CHO from liver glycogen
30% from gluconeogenesis
in exercise, rate of hepatic glucose release related to what
exercise intensity (contribute to 90% CHO)
in trained athletes, how will hormone concentrations change during exercise ?
they will have an attenuated response
what will happen to intramuscular triglyceride content in trained athletes ?
increase concentration due to better fat utilization
how will rate of lactate accumulation change in trained athletes ?
decrease
how will rate of muscle glycogen and glucose change in trained athletes ?
decrease
