fat synthesis Flashcards
3 questions to ask
do you have enough energy
do you have enough stored carbs
what should i do now
Fatty acid synthesis
you build fatty acids when you consume excess carbs
when dont you build fatty acids
when you consume excess fats
how does glucose get in the cell
it does not diffuse in the cell directly
2 transport mechanisms
what are the 2 transport mechanisms for getting glucose into the cell
sodium independently facilitated transport system
sodium monosaccharide co transport system
sodium independently facilitated transport system
glucose transporters GLUT
moves down the concentration gradient
sodium monosaccharide co transport system
ATP dependent
transports glucose AGAINST concentration gradient
epithelial cells of intestine, renal tubules and choroid plexus
What are two glucose transport proteins
GLUT 2
GLUT 4
glucose galactose and fructose
dietary glucose- out of the intestine (into the blood)
into the liver, kidney, pancreas B-cells
insulin independent
GLUT 2
glucose into muscle and adipose tissue
stimulated by insulin
stimulated by low energy charge (AMPkinase)
facilitated diffusion
GLUT 4
what are glucose transport statistics
in the absense of insulin only 5% of the total transporter pool is found on the cell surface
exercise or insulin result in a 10fold increase in glucose uptake in skeletal muscle
about 90% of insulin stimulated glucose uptake occurs in skeletal muslce
adipose tissue only accounts for 10% of insulin stimulated glucose uptake
what does exercise increase the number of
increases the number of GLUT 4 proteins in skeletal muscle
what does exercise stimulate the accumulation of
GLUT 4 in the cell membrane for 1-2 hours after exercise
what happens when adding a phosphate to glucose do
the glucose concentration in muscle remains low and glucose keeps coming
where is glucose
in the blood
what happens when muscle energy is low
glucose 6 phosphate runs through glycolysis prep step and krebs to make ATP
what happens when glycogen is low
glucose 6 phosphate is converted to glycogen
eating carbs does what
elevates blood glucose
when having a elevated blood glucose what happens
elevated insulin is caused
what happens with a elevated insulin
fat and muscle glucose transport
is the muscle full of glycogen after fat and muscle glucose transport
NO glucose is stored as glycogen
is the muscle full of glycogen after fat and muscle glucose transport
YES glucose goes to the liver
how does glucose enter the muscle
via facilitated diffusion
what does high energy and plenty of glycogen stores inhibit
PFK
when PFK is inhibited what does it cuase glucose 6 phosphate to do
accumulate and inhibit hexokinase
what does higher glucose concentration in muscle inhibit
inhibits facilitated diffusion of glucose
glucose goes to the liver
glucokinase
glucokinase
lower affinity
stimulated by insulin
not inhibited by product
glucokinase does what
runs glycolysis
glycolysis runs for
energy and raw material
glucose goes to the liver ultimately for
fat building
glucokinase
lesser affinity for glucose
not inhibited by its product
stimulated by insulin
stimulated by fructose
what does a increase of glucose satisfy
satisfies the low affinity of glucokinase
what is the liver a primary site for
for fructose metabolism
what does the liver express
frutokinase and triokinase
what does fructose stimulate
stimulates glucokinase
what is the liver a primary site for
fructose disposal
what are the enzymes essential for fructose metabolism and are highly expressed in the liver
fructokinase
triokinase
limited expression in muscle and adipose tissue
where is the fructose 1 phosphate pathway
in the liver
what is the entry point into glycolysis
glyceraldehyde 3 phosphate
what does a low dose of fructose cause
causes a 3fold increase in net liver glycogen synthesis
what do smaller amounts of fructose cause
causes the release of glucokinase from a regulatory protein
what does not inhibit glucose 6P
glucokinase
acetyl CoA to
FAT
where does fructose enter at
DHAP G3P
what does F6P normally binds to the regulatory protein and what is inhibited
glucokinase
F1P binds to the regulatory protein and GK is
set free and activated
fructose and fat the liver preferentially takes
in fructose
the liver has more what
fructokinase and triokinase enzymes
what does fructose stimulate
GK
what does fructose and fat produce
more acetyl CoA and ATP
building blocks and energy for building fatty acids
excess carbs and protein in the diet do what
synthesize FA
store as TAG
where is the pathway primarily
LIVER
lactating mammary glands
adipose tissue
what is the FA synthesis location
cytosol Beta oxidation
Building fat
Eating carbs raise blood glucose
insulin is secreted
glucose enters the cells
energy requiring
ATP
reduced conenzyme
nicotinamide adenine dinucleotide P (NADPH)
acetyl CoA supplies
carbons for the FA chain
glycolysis>pyruvate>acetly CoA
AA catabolism
Acetyl CoA needs to get to the matrix to the cytosol is a
problem
high sugar intake increases what
ATP production
what can the acetyl portion of acetyl CoA can be transported as
citrate into the cytosol
why do we need high energy
to build fat
citrate is where
in the inner mitochondrial membrane
citrate to acetyl CoA by
ATP added to ADP+Pi
citrate lyase
CoA added
carboxylation of acetyl CoA
acetyl CoA to malonyl CoA y acetyl CoA carboxylase coenzyme biotin
malonyl CoA inhibits what
CPT I and fat burning
what does the reaction of acetyl CoA and Malonyl CoA also require
CO2
ATP
synthesis of malonyl CoA
acetyl CoA to Malonyl CoA by acetyl CoA carboxylase conenzyme biotin
what is the rate limiting and regulatory step of FA synthesis
acetyl CoA carboxylase ACC
Short term regulation of ACC inactive is a what
a protomer=subunit
polymerization= combining subunits
what is short term regulation of ACC activated by
citrate
what is short term regulation inactivated by
long chain fatty acyl CoA
end product=depolymerization
acetyl CoA carboxylase regulation is stimulated by
citrate
insulin
acetyl CoA carboxylase regulation is inhibited by
malonyl CoA
palmitate-end product
epineprine
glucagon
metformin and type 2 diabetes
inhibtion of ACC
activates AMPK
inhibits ACC and fatty acid synthase
lowers blood glucose
the reaction all part of fatty acid synthase the next four steps
condensation
reduction
dehydration
reduction
condensation is Acetyl ACP and Malonyl ACP to?
Acetoacetyl ACP by beta ketoacyl ACP synthase
REduction Acetoacetyl ACP to D 3 hydroxybutyryl ACP by
beta ketoacyl ACP reductase
synthesis
cytosol acyl carrier protein adding 2 carbon units malonyl ACP NADPH consuming ATP
degradtion
Mitochondria Coenzyme A donating 2 carbons units acetyl CoA NADH FADH2 Making ATP
conditions that stimulate
high energy charge increased acetyl CoA increased NADH and FADH2 increased citrate increased sugar (glucose fructose) insulin
key enzymes
citrate lyase
acetyl CoA carboxylase
fatty acid syntase CRDR
TAG synthesis in the what
mitochondria
elongation is accomplished through
elongases and requires NADPH
desaturation is accomplished through
desaturates by adding double bonds
what are separate enzymatic processes
mitochondria
smooth ER
what can humans not create
double bonds beyond the 9-10th carbon
NADPH where does it come from
pentose phosphate pathway
malate-pyruvate in cytosol
NADPH source of electrons in?
synthesis
Fatty acids are what kind of molecules
highly reduced
remember reduction is gain of hydrogen and electrons
dehydraton D3 hydroxybutryrl ACP to Crotonyl ACP
by beta hydroxyacyl ACP dehydratase remove H2O
reduction 2 by Crotonyl ACP to Butyryl ACP by
Enoyl ACP reductase
Palmitate (16:0) when does this process stop
when we have 16 carbon palmiate
fatty acid synthesis
reduction
dehydration
reduction
fatty acid synthase
CRDR Condenses-adds molonyl CoA Reduces- with NADPH Dehydratase Reduces- with NADPH
release the fatty acid
palmitoyl thioesterase
last step of FAS
cleaves thioester bond and releases saturates palmitate
Update: Butyryl last 3 carbons are? still attached to? Transfer the butyryl chain to the what site? add another? when does growth stop
(4 carbons) hydrogen saturated ACP holding site (cysteine) add malonyl CoA and repeat at 16 carbons of palmitate
long term regulation ACC
high calorie/high carb diet
increase ACC synthesis which increase FA synthesis
long term regulation ACC
low calorie/ high fat diet
decrease ACC synthesis which decreases FA synthesis
long term regulation ACC
upregulated by insulin
increased response/increased receptors
increase ACC synthesis which increase FA synthesis
multi enzyme complex is
FA synthesis
one portion of the molecule is ACP
one portion of the molecule is ACP
acyl carrier protein ACP
similar to coenzyme A
terminal thiol group at the end of an arm
short term regulation of ACC
reversible phosphorylation
AMP- activated protein kinase AMPK- phosphorylates and inactivates ACC
short term regulation of ACC
reversible phosphorylation
can be activated by cAMP dependent PKA
epinephrine and glucagon increase cAMP which phosphorylates and inactivates ACC
insulin dephosphorylates and activates ACC
