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Lecture 7

BCH210H1 Lecture Notes - Lecture 7: Threonine, Beta Blocker, Fructose


Department
Biochemistry
Course Code
BCH210H1
Professor
Michael Baker
Lecture
7

Page:
of 4
Recall:
pyruvate accumulates because not enough oxygen
muscle is not supplyed with enoughh blood- if not enough blood goes in muscle cells that
mean red blood cells can't provide enough oxygen
lactate accumulates – PH drops – muscle cramping
NADH converted to NAD+
what's the advantage of pyruvate converted to lactate with respect to glycolysis, if it can't go
to mitochondria?
How is the conversion of NADH to NAD+ advantageous if you are relying on glycolysis to
generate ATP? True
Advantageous because – you are reducing the products (pushing the equilibrium to the
right) and the NAD+ can go back in glycolysis and help generate ATP – it's a substrate
most people can't convert lactate back to pyruvate – so goes back to blood and recycled in the
liver
very useful fuel gone to waste
Soon- yi continuatio
Soon-yi starts to run over the sand, but her existing blood glucose cannot readily sustain muscle
glycolysis
she needs more fuel for glycolysis and her muscle glycogen will provide this
also needed to maintain blood glucose levels
you can go into hypoglycemia and collpase if blood sugar not maintained at 3 mM
side note – never eat and run – cramps – oxygen needed for digestion
Glycogen
substantial resource of glucose
glycogen granuale can be broken down:
as a source of energy
source of blood sugar
takes a longer time to access fat than glycogen(breaks down more easily)
polymer of glucose (alpha 1-4 links primarily but could be alpha 1-6 at the branch point where
the oxygen on carbon 1 connects to the ch2O6 on carbon 6)
much more branched than starch (amylopectin)
stored in muscle and liver
to supply energy for muscles to keep on running
liver supports blood sugar levels
***can't just rely on fat storage, need glycogen to last you the entire race- why is that? Fat
break down gives you energy too when it goes through mitochondrial reactions?
It's because pyruvate can make oxalocetate
Combining fuels is the best way to go- glycogen and fat
Soon-yi has not eaten for 10 hours , blood sugar levels decreases, she releases two hormones into the
blood
adrenaline/ epinephrine released – plays a big role in muscle contraction
released during stress or exercise
regulate breakdown of glycogen in muscles- how to acess glycogen in the muscles to keep
glycolysis and contraction going in the muscles
adrenergic receptors in muscles (skeltal muscle) and heart
heart rate goes up with adrenaline
leads to elevated blood pressure = hypertension
Pathway for muscles
epinephrine binds to the receptors (adrenergic receptor) on the muscle cells and actates
intracellular signalling pathway
This activates Adenyl cyclase (through the whole G-protein alpha unit binding) releases cAMP
from ATP
cAMP = the second messenger as adrenaline does not actually enter the cell
cAMP initiates a cascade of enzyme activation in the muscle cytoplasm- amplification effect
cAMP activates Protein Kinase A (PKA)- phosphorylates proteins at serine and threonine
residues, using ATP
PKA phosphorylates phosphorylase Kinase making it active
calcium ions increase in muscle cells to stimulate contraction during exercise
this rise in calcium ions also activates phosphorylase kinase
Phosphorylase kinase phosphorylates glycogen phosphorylase making it active
glycogen phosphorylase b (GPb) = the inactive form
glycogen phosphorylase a (GPa) = the active form
glycogen phosphorylase also activated by rising concentrations of Pi from the
hydrolysis of ATP during exercise
GPa then attacks the glycogen chains
inorganic phosphate is used by GPa to cleave the glycosidic bond
end products = alpha- D- glucose-1-phopshate
Glycogenolysis- endocrine controlled breakdown of glycogen
alpha-D-glucose-1-P eventually converted to alpha-D-glucose-6-P in the muscles via
phosphoglucomutase
Now alpha-D-glucose-6-P rapidly flows into glycolysis and provides a burst of fuel for
the growing energy neeeds of Soon-yi's muscles- because a lot of glucose released
In this same pathway when adrenaline is released, PKA phosphorylates glycogen synthase (the
enzyme that produces muscle glycogen)- inactivating it
this allows for breakdown of muscle to continue on
same end effect as epinephrine but different targe enzymes
thus soon-yi mainly use catabolic, not anabolic patway for fuels
This response is seen in muscles as well as liver
glycogenolysis is regulated by
hormones – epinephrine, glucagon and insulin
calcium levels – increased due to muscle contraction
inorganic phosphate- increased during the hydrolysis of ATP
Glycogen phosphorylase- how it actually works
it acts as a phosphorylase not a hydrolase
it breaks the glycosydic bond (only alpha 1,4 not 1,6) using an inorganic phosphate not water
when you eat starch, amylase breaks it down in the intestine using water
maltose is broken down by maltase using water
glycosydic ester link has energy that can be preserved if you break the bond using Pi
glucose units coming from glycogen gives you more ATP then from the blood because you are
missing the first step that require ATP to convert into glucose 6 phosphate
you already have a phosphate added to the glycogen in position 1
To control blood pressure
- Block the beta agenergic receptors with a beta blocker (adrenaline can't bind to it) – block the
output of heart- block the production of hypertension
- You have to blend the number of medicine
- If you give someone water pills- urinate more- urination takes the water away the blood – blood
levels go down and hence blood pressure comes down
oIf he takes his water pills on the weekend when adrenaline (stress related) not release =
hypotension – will faint
- You need blend of medicines
- Anomeric carbon = carbon 1 in glucose (Fructose anomeric carbon= C2)
Conversion of glucose-1-phosphate to glucose 6- phosphate
- using an isomerase- phosphoglutomutarase- replaces the phosphorylation from one position
with the 6th position
- isomerase can go either way – glucose-1-phosphate and glucose -6-phosphate exist in
equilibrium (they have the same energy)
- Say you have a lot of sugar coming in your body- glucose-6-phosphate, it will go to glucose-1-
phosphate and help resynthesize glycogen
Soon-yi= a lot of energy when running
glycogen reserves release glucose = glucose -6-phosphate(the substrate) increases
PFK- 1 increased by AMP levels
PK increased – by other intermediate within glycolysis
side note- you don't want to eat when running- body switches to anabolic pathway – can't access the
catabolic pathway for energy
The roles of different tissues
1. Muscle- the body builder
uses up fuels -doesn't share -consumers
this is important because you want the muscles to to stay dedicated to contraction and not
lose fuels
muscle glycogen stays in muscle and goes through glycolysis there
2. Fat
couch potato
storage depot for high calorie fuel – rather inactive
fat will only break down after continued, substantial work
extra glucose you eat that is more than your ability to make glycogen and outside of your
energy needs (you don't burn it off in activity) – it turns into fat
fat = a lot of energy
3. Brain
like sheldon- the computer guy- controls all the circuits
relies on continuous supply of glucose as fuel, and blood to deliver the glucose
has no stored fuels/energy
consumer -relying on home delivery
that's why when you go in hypoglycemia- not enough sugar in the blood to transport to
brain – you can lose consciousness
4. Liver
the singe parent
the mother who tries to meet every need (nutrients+energy) of the family (all other tissues)
centre of your intelligence is focused here- very detaile person