Biochem Exam 3

11/6/2014 11:22:00 AM

Multiple Fates of Pyruvate

Fermentation: regen NAD+; remove pyruvate
o No energy gain; toxic accumulation
Respiration
o Slow; LOTS of ATP; CO2
NAD+/NADH role catalyzes hydride transfer
Glycolysis Regulation: Allostery
ATP high; low glycoloysis
ATP low; high glycolysis
Feedback Inhibition
o Downstream products inhibit PFK
Liver in Process
LDH: pyruvate to lactate which is moved to liver
----------------------------------End of Exam 2----------------------------------Gluconeogenesis Begins
Previous lectures
Anaerobic conditions: muscles produce lactate from pyruvate
Yield: 2 ATP
Cori Cycle

Regeneration of glucose from lactate and protons;

gluconeogenesis
Mostly occurs in liver
Gluconeogenesis
Not a reversal of glycolysis; remember that there are 3 irreversible
steps which need to be circumvented; other 7 steps are simple
reversal
Rather than reversal: PyruvatePEP; Fructose-1,6bisphospahteFructose-6-phosphate; Glucose-6phopshateglucose
Energy CONSUMING process
Anabolic process (synthesis)
PyruvatePEP
PEP is a higher energy molecule than pyruvate; have to hydrolyze
ATP to get it there
PyruvateoxaloacetatePEP

Pyrave oxaloacetate = ATP hydrolysis (~7kcal/mole); pyruvate

carboxylase
OxaloacetatePEP = GTP hydrolysis (~7kcal/mol); PEPCK
Happens in mitochondria
CO2 is reproduced (consumed first and remade with making of PEP)
STEP 1
o Biotin cofactor in attaching CO2 to pyruvate to form
oxaloacetate
o Pyruvate carboxylase
o Bicarbonate rips phosphate from ATP and reacts with biotin-

enzyme complex to form CO2-biotin-enzyme complex (first

two steps)
o That complex reacts with pyruvate through substitution to
yield biotin-enzyme + oxaloacetate
Biotin
o Usually found as a protein conjugate; concerned biotin reacts
w/ activated CO2
Mitochondria
Inner membrane highly selective; oxaloacetate CANNOT move in
and out
Oxaloacetate is taken out in the form of malate via transport
system and reoxidized to oxaloacetate in cytosol (carbonyl carbon
of oxaloacetate is reduced to OH- to form malate)
Glucose-6-phosphate to glucose happens in endoplasmic reticulum;
irreversible step
G6P converted to glucose + Pi by glucose-6-phosphatase
SP = Ca2+ protein necessary for phosphatase activity
T1 = transport G6P into ER Lumen
T2 (Pi) and T3 (glucose) to transport products into cytoplasm
Glucose-6-phosphatase and SP for reaction
Final Thoughts: glycolysis and fermentation happen completely in cytosol;
but gluconeogenesis requires multiple organelles

Lipids

11/6/2014 11:22:00 AM

Gluconeogenesis: non-carb to glucose; ATP consumption (2 pyruvate->1

glucose)
Oxaloacetate transportation happens by converting it to malate;
o Oxaloacetate (mit.) + NADH (mit.) + H+ (mit.) + NAD+
(cyt.) Oxaloacetate (cyt.) + NAD+ (mitoc.) + NADH (cyt.)
+ H+(cyt.)
1 Glucose = 6 ATP consumed through gluconeogenesis
Can use pyruvate, lactate, amino acids, and glycerol
Using glycerol, it costs 1 ATP to convert to Glyceraldehyde-3-P and
to glucose (2 per two molecules of glycerol, etc)

Net energy loss (2 ATP by glycolysis; -6 by gluconeogenesis)

LactatePyruvate Glucose (liver)
Reciprocal regulation of glycolysis and gluconeogenesis

ATP stops glycolysis by inhibiting PFK

Fructose-2,6-bisphosphate: promotes glycolysis; inhibits
gluconeogenesis by inhibiting fructose-1,6-bisphosphatase;
activates PFK promoting glycolysis

Blood Glucose dropsPKAPhosphorylase kinase phosphorylates glycogen

phosphorylase
--------------------------------Lipids Begins------------------------------------Lipids-hydrophobic; amphiphilic small molecules
Fatty acids = hydrocarbon chain + carboxylic acid
n = linear chain (no branches)
cis-9 = double bond between C9 and C10 and it is in cis
Section 12.2 Berg
Lipids = water insoluble biomolecules; highly soluble in organic
Phospholipids; glycolipids; cholesterol

Ester connects fatty acid to glycerol

Phospholipid = phosphate to alcohol; both to glycerol and fatty acid
chains attached to glycerol
Glycolipids = contains sugar molecules; usually contain sphingosine
in animals
Cholesterol = multiple (4) rings; steroid nucleus
Phospholipids
Have polar and non-polar regions
Several different polar head groups for phospholipids
Glycerolipids
Weird; have sugar heads that are hydrophilic
Cholesterol
Hydrophobic
More rigid than phospholipids; four rings
Membrane Proteins
Integral inside the membrane itself
Peripheral usually water soluble so they are attached to the
membrane
o Attach hydrophobic groups to protein and send it into the
membrane (GPI linkage)
o Often found in extracellular proteins
Cholesterol
o More cholesterol = less fluidic
Proteins and lipids move laterally
Lipids can FLIP
Membrane is heterogeneous and dynamic (changes over time and space)

Lipid Rafts are a thing

Signaling proteins enriched in cholesterol rich subdomains
Differ from regular bilayer due to enriched area

Mitochondrial Metabolism

11/6/2014 11:22:00 AM

Pyruvate Dehydrogenase links glycolysis to TCA

PDH
o Mitochondrial enzyme complex
o Transfers a hydride to NAD+ to form NADH
o Net Rxn: Pyruvate + CoA + NAD+ acetyl-CoA + CO2 +
NADH + H+
Points to remember about PDH
o PDH highly regulated
o Made of multiple copies of 3 Enzymes (E1, E2, E3)
o Uses several cofactors (TPP, lipoic acid)
Rxn intermediates delivered to next active site covalently
Removes carbon from Pyruvate
Generates NADH
Cleaves Pyruvate between C2 and C3 (between carbonyl
carbons), leaving the carbon w/ 2 oxygens to become CO2
and the other to become acetyl CoA
o Be able to answer which carbons in glucose become
carbon dioxide
o
o
o
o
o

CoA
Vitamin B5 Derived Cofactor
Non-protein required for enzymes
CoA-SH
Thiol group is very important to function
Takes carboxylic acid and attaches to something else
CoA-SH + RCO2H CoA-carboxylic acid + H20
Used as an Acyl carrier
Acetyl CoA

Citrate

Roles: TCA; Fatty Acid Synthesis; Cholesterol Synthesis; histone

acetylation (regulatory roles)
After formation of acetyl-CoA, it immediately remains in the
mitochondrial matrix
Reacts w/ oxaloacetate to form citrate through citrate synthase
Oxaloacetate + Acetyl CoA + water citrate + CoA
In this way, CoA is reformed to become Acetyl CoA again

Generated from oxaloacetate and acetyl CoA through citrate

synthase
Can be diverted to generate cytosolic acetyl CoA mammals
Forms cis-Aconitate and then form isocitrate; through Aconitase
Isocitrate Dehydrogenase (IDH)
Generates NADH and CO2
Forms -ketglutarate

o Important for amino acid synthesis and other processes

Genes (IDH1/2) are most frequently mutated in human cancer
In cancer, 2-hydroxyglutarate is created from the mutated gene,

which stimulates cell growth

-ketglutarate becomes Succinyl Co-A through interaction of CoA and NAD+;
yielding CO2 and NADH
Succinyl-CoA is then converted to Succinate, yielding ATP or GTP
SuccinateFumarateMalate>OAA
First transformation requires FADFADH2
FAD (Flavin Adenine Dinucleotide)
Different from NAD+
Another cofactor that causes oxidoreduction roles in cells
Reduces to FADH2
TCA Cycle
Acetyl CoA + 3NAD+ + FAD + ADP + Pi + H20 2CO2 + CoA + 3
NADH + FADH2 + ATP + 2H+
Net yield: 2CO2 + ATP + 3NADH + 1 FADH2
Pyruvate into Citric Acid cycle = 4 NADH (1 from conversion of
pyruvate to Acetyl CoA)
PDH Regulation
Inhibit PDH by phosphorylating it
PDH Kinase
TCA regulated in irreversible steps (pyruvate to Acetyl CoA, Isocitrate to
ketoglutarate, ketoglutarate to succinyl CoA)
Energy Charge = (ATP + 0.5ADP/ ATP + ADP + AMP)
TCA interaction w/ other pathways
Pyruvate carboxylase makes oxaloacetate from pyruvate
(gluconeogenesis)
Fatty acids can be degraded to Acetyl-CoA

Glutamine can be converted to Glutamate and converted to

ketoglutarate to feed TCA cycle

Oxidative Phosphorylation

11/6/2014 11:22:00 AM

Summary of TCA
1 ATP; 3 NADH; 1 FADH2 + 2CO2
Electron Transport Chain (ETC)
NADH and FADH2 in mitoc. oxidized to NAD+ and FAD
Electrons serially transferred to O2 to become H20
Mitochondrial membrane
Protons pumped out
Four Complexes; 3 pump protons (not Complex II)
NADH Reductase (Complex I)
o Oxidizes NADH to form NAD+

o 2 electrons and 2 H+ from NADH and delivered to Q

o 4 H+ moved to intermembrane space
Succinate Dehydrogenase (Complex II)
o Two electrons and 2 H+ from FADH2 and delivers them to Q
o Does NOT pump H+ to intermembrane space
o FADH2 not as stable as NADH so the electrons and protons
are immediately transferred to coenzyme Q after FADH2
generation
Coenzyme Q = ubiquinone
o
o
o
QH2
o

Quinone compound (2,5 cyclohexene w/ two oxygens)

Membrane soluble
Takes 2 electrons and 2 protons to form QH2
delivers electrons to Complex III (cytochrome C reductase)
Q cycle- complex III pumps protons; relays electrons to
cytochrome C
Complex III has two Q binding sites (Qo and Qi)
Cytochrome C binds to outer side of complex III
Oxidized Q binds to Qi site

Reduced QH2 from Complex I or II comes to Qo site

QH2 gives one electron to cyt C; one electron to Q in Qi
site and 2 protons to outside
Oxidized Q moves out of complex and another QH2
enters Qo site
4H+ to intermembrane space
Cytochrome C
o Water soluble (small molecule) protein w/ a heme

Problem

o Takes one electron each time from QH2 and delivers it to

Complex IV
o Works twice per QH2
Complex IV
o Moves elects from cytochrome C ot 1/2O2, moving 2 more
protons to intermembrane space
Overall assume, 2.5 and 1.5 molecules ATP from each mitochondrial
NADH and FADH2 molecule
of lonesome NADH from glycolysis
Cannot enter mitochondrial matrix to enter ETC
So how much ATP value does this have?
o Electrons from NADH are transported across mitochondrial
membrane via shuttles
o G3P Shuttle ATP = FADH2 power
NADH reduces DHAP to G3P in cytoplasm
G3P Reduces FAD to FADH2 which is oxidized to FAD
making QH2 from periphery
o Malate-asparatate shuttle = mitochondrial NADH power
Malate to aspartate inside w/ production of NADH

Aspartate to malate outside w/ production of NAD+

Only works if NADH/NAD+ ration is higher in cytosol
than matrix

F1 F0 ATP Synthase
Mitochondrial ATP synthase
F0 transports H+ from outside to inside; unidirectional rotation
F1 uses rotational energy to produce ATP from ADP + Pi
F1 Subunit
Composed of 9 subunits

Alpha3, Beta3, Gamma, Delta, epsilon

Alpha and Beta are hexamers; both bind nucleotide, but only B
participate in reaction
Beta binds tightly to ATP bringing the energy level down below ADP
Loose conformation binds ADP and Pi; second Beta converts to ATP;
Third releases
Gamma rotation causes change in conformation allowing release
F0 subunit

a subunit composed of hydrophobic outside and hydrophilic halfchannels

c subunit has aspartic acid in middle of transmembrane helix
when aspartic acid residue is in membrane, it will be protonated
when exposed to polar environments, it will be de-protonated
F1F0 Summary
Proton from inter-membrane space to matrix
Rotates c subunit of F0
Rotates Gamma of F1
B conformation changes

ATP synthesized from ADP and Pi

Fatty Acids

11/6/2014 11:22:00 AM

Mitochondrial ATP-ADP Translocase

Controlled by electron potential (only respirating mitochondria take
ADP); proton gradient driven
ADP entry is coupled with ATP exit
Quarter of energy from ETC is used to regenerate membrane
potential used by enzyme
Inhibition of this inhibits cell respiration
ATP needs 4H+ to move through and ADP needs 3H+ to move
through
1H+ removed from proton gradient

NADH and FADH2 are worth only 2.5 and 1.5 ATP per molecule
because ATP-ADP translocase increases cost of protons to 4 per ATP
molecule generated
Places NADH is generated
Glycolysis 2 per glucose
PDH 1 per pyruvate (so 2 per glucose)
TCA- 3 per pyruvate (so 6 per glucose)
------------------------------Fatty Acid Stuff-----------------------------------Fatty Stuff
Oil Red O: chemical that turns pink when it gets into lipids
ACL stained pink; major source of fatty acid synthesis
1st Step
Acetyl CoA becomes malonyl CoA
CO2 attached to Acetyl CoA with ATP hydrolysis (similar to
oxaloacetate formation by biotin from pyruvate)
Acetyl CoA Carboxylase (ACC)
Highly regulated
Acyl Carrier Protein (ACP)
ACP replaces CoA as CoA is not stable in water and this is used for
the rest of fatty acid synthesis
Fatty Acid Synthase
Highly modular complex
Multi-enzyme protein complex
Malonyl ACP is made with release of CO2 and ACP in synthase

NADPH comes in with a proton and oxidized to NADP+ to make

alcohol and add a hydrogen to second to last carbon

NADPH
NADPH used in major anabolic processes
Anti-oxidant against oxidative stress in cells
Used to produce reactive oxygen in immune cells to kill
microorganisms
Completely reduces second half of the malonyl ACP to a
hydrocarbon looking thing
Releases water when OH leaves

Each cycle generates 2 more carbon attachments; 2 NADPH

consumed; cleave results in fatty acids
Fatty acids attached at OH and Phosphate group of Glycerol-3-phosphate
Phospholipids
De Novo Synthesis overridden when theres a ton of fatty stuff in your food
Fatty Acid Oxidation (beta oxidation)
Mitochondrial process
Generates CoA (some ATP) from fatty acids
Cyclic process

Each cyle removes 2 carbons from carboxyl ends and taken out and
become acetyl CoA
Each produces 1 FADH2 and 1 NADH and 1 Acetyl CoA, but at the
end there will be an extra Acetyl CoA remaining so it/s always 1+
(number of NADH) = number of acetyl CoA from molecule
Fatty acids for energy
Triacylglycerol cleaved into fatty acids and glycerol
Fatty acids fatty acid coenzyme A and move into mitochondria
Fatty acid CoA cannot enter directly
o
o
o
o

Uses Carnitine shuttle

Coverted to acyl carnitine and enters mitochondria
Inhibited by malonyl CoA
High levels of NADH in mitochondria also inhibits fatty acid
translocalization

Amino Acid Metabolism

11/6/2014 11:22:00 AM

If there isnt enough oxaloacetate, there will not be anything for TCA cycle,
leaving extra acetyl CoA
This is converted to ketone bodies which are used by other organs
for energy supply
Some diseases have nail-polish remover like-smell
Cholesterol Synthesis
Same de novo vs. food salvage process
-----------------------------End---------------------------------------------------Amino Acid Metabolism
Nitrogen Fixation

N2 to NH3 by some bacteria

Nodules in rhizobium (soil bacteria) form reaction: N2 + 3H2
2NH3
2/3 nitrogen fixation
Ammonia reacts with ketoglutarate to form glutamate, consumes one NADH
or NADPH
Goes from achiral (ketoglutarate) to chiral (glutamate)
Sometimes Glutamate becomes glutamine by interacting with another
ammonia
Amine is donated from glutamate/glutamine and regenerate their original
molecules (glutarate or glutamine)
Pyridoxal Phosphate: vitamin derived cofactor that transfers ammonia and
then switches between ketone to amine or amine to ketone
Stereospecific
Generates L-amino acids (S-form)
Amino Acid Degradation
First step is to give up an amine to Alpha-ketoglutarate to form
glutamate/-tic acid
Amine is used by carboxyphopshate to form carbamic acid
This is converted to carbamoyl phosphate
Carbamoyl Phosphate
Reacts w/ ornithine to form citrulline
Citrulline
Conjugated to aspartate to form argininosuccinate
Breaks down to form arginine and fumarate

Ornithine regenerated when producing urea by breaking arginine into

ornithine and urea
Above = urea cycle/ornithine cycle

Pentose Phosphate Pathways

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PPP

Precursors for amino acid synthesis

Diverts a glycolysis intermediate
Produces starting material for nucleotide/histidine biosynthesis
(ribose-5-phosphate)
o Starting material for aromatic amino acid (erythrose 4phosphate)
Major source of NADPH
Oxidative Phase
1st step

o Start with Glucose-6-Phosphate

o G6P dehydrogenase (G6PD) catalyzes reaction
o NADPH generated
nd
2 step
o Hydrolysis of the product from first step to form 6phosphogluconate
3rd step
o Decarboxylation and oxidation bt 6-phosphogluconate
dehydrogenase

o Removes CO2 6-phosphogluconate and product becomes

Ribulose-5-phosphate
o NADPH generated
Non-oxidative Phase
Mingle mangling produces Glyceraldehyde-3-phosphate (glycolysis)
o Erythrose4-phosphate (precursor for aromatic amino acid
synthesis)
o Ribose5-phosphate, xylulose-5-phosphate (precursor for
nucleotides)
o Fructose-6-phosphate (glycolysis)
o Sedoheptulose-7-phosphate
Ribulose-5-phosphate
Stays in PPP or isomerizes to ribose-5-phosphate for nucleotide
synthesis
Transketolase takes 2C from one xylulose-5-phosphate and adds it
to a ribose-5-P, making G3P (enters glycolysis or stays in PPP) and
Sedoheptulose7-P

Transaldolase
Takes 3C from sedoheptulose-7-P and generates fructose-6-P with
erythrose-4-P
Overall
2 NADPH generated/G6P
Non-oxidative phase: other metabolic precursors generated
If no other processes were begun, 3G6P becomes 2 fructose 6 P
and 1 glyceraldehyde 3 P for glycolysis
Energy losing process
o More loss w/ more loss of carbons in R5P or E4P
-------------------------------Nucleotide Biosynthesis------------------------Nucleotide
Base + ribose + phosphate (s)
Nucleoside = nucleotide w/o phosphates
Cellular metabolism as energy source
Precursor to DNA/RNA etc
Consumption
At any time, the amount of nucleotides present is not enough to
perform duplication of genome in E. coli

Ribose-5-P with ATP is made to PRPP

Step highly regulated as PRPP cant be used for anything other than
nucleotide/histidine biosynthesis
After PRPP generated
Salvage Pathway: 1 step to get adeneine and form nucleotide by
replacing PPi in the PRPP
Can also replace w/ UMP, CMP, TMP
Pyrimidine Biosynthesis
Begins w/ bicarbonate to carbomoyl phosphate process

o Bicarbonate acquires phosphate from ATP then loses it to take

NH2 then loses H on OH to get another Phosphate and form
carbamoyl phosphate
Cyclizes with aspartate to form orotate
Orotate reacts w/ PRPP to form orotidylate and eventually UMP
UMP becomes UDP and UTP (RNA)
UTP can be converted to CTP (replace O with NH2) and TTP can be
synthesized from UTP

Purine Synthesis
Gln used as NH2 donor to PRPP
Generates IMP which is converted to AMP or GMP (AMP needs GTP,
GMP needs ATP hehe)
Overall nucleotide biosynthesis = messay and consumes LOT of energy
Suppressed when
No Pi
Too much ADP

Regulation of Carbohydrate Metabolism11/6/2014 11:22:00 AM

Langerhans islets
Contain endocrine cells
Alpha and Beta Cells
o Alpha converts glucagon to make more glucose
o Beta makes insulin to reduce blood glucose
How B cells determine when to secrete insulin
Blood glucose high
GLUT2 in B cells imports glucose into cell
ATP in cell increases
ATP closes ATP gated K+ channel
Ca2+ import gets activated, stimulating insulin secretion
Weak affinity glucose transporter = key point
Km is similar to blood glucose concentration range
Transport range is dependent of glucose concentration in blood
How A cells determine when to secrete glucagon
Blood glucose low
GLUT2 in A cells import glucose into cells slowly
o ATP lowers
K+ pump gets inhibited

Insulin

Ca2+ in cell stimulates glucagon secretion

Peptide hormone from beta cells

2 chains w/ disulfide bonds w/ more carbs sometimes
signals liver and other organs to take up glucose by telling them
theres too much
Glucagon
Elevates blood glucose level
Peptide based hormone

Binds to liver cells and activates glycogen phosphorylase (no idea

how doe); breaks down glycogen to glucose-1-phosphate to form
glucose and release to blood
Adrenaline
Amino acid derived hormone from adrenal gland
Functions like glucagon but was easier to synthesize
Glycogen
Polymer of glucose

Gets a monosaccharide replaced with a phosphate group, releasing

that G1P
Phosphorylation: simple addition of phosphate
Phosphorylase: using phosphate as nucleophile to break something down
Glycogen Phosphorylase on Glycogen
G1P becomes Glucose 1,6-bisphosphate and then glucose 6
phosphate
This can either go through gluconeogenesis or through glycolysis
Experiment
Grind up livers and apply epinephrine and glucagon
Bunch of different glycogen phosphorylase stuff
Found that cAMP turned glycogen phosphorylase into active R form
cAMP activated via GPCR
PKA
2 R and 2 C subunits
R units autoinhibit C subunits
cAMP binds to R (2 each cooperatively) and dissociate them from C
subunits
phosphorylates phosphorylase kinase which phosphorylates
glycogen phosphorylase to activate it
Also phosphorylates PFK2 to inhibit Fructose-2,6-bP synthesis
Suppresses glycolysis and increases gluconeogenesis
Insulin signaling
Binds to Trk receptor on cell surface
Second part comes together to form dimer
Phosphorylation happens inside cell
IRS (insulin receptor substrate) becomes phosphorylated
Recruits PI3K

o Contains SH2 domain that binds to phosphorylated tyrosine

o Phosphorylates PIP2 to become PIP3
PIP3
o Recruits cytosolic proteins w/ PH domains and relocates them
to membrane
o Recruits PDK1 and AKT
Causes survival and ribosome synthesis and glucose
uptake

Point is to show translocation of glucose transporter from intracellular

vesicles to plasma membrane
Insulin goes upglucose sucked into the cell
Glycogen synthase also activated
Diabetes
Type 1 = autoimmune
Type 2 = normal insulin level

Cholesterol Metabolism

11/6/2014 11:22:00 AM

Food blocks De novo cholesterol synthesis

Can make various steroid hormones; cell membrane structure and function;
synthesis of vitamin D; bile acids for fat metabolism
Food cholesterol synthesis
Hamburgerstomachcarbfatty acidcholesterol
Cholesterol too hydrophobic to get into body
Triacylglycerols w/ some proteins surround it in vesicles
(chylomicrons) and enter blood
Moves to liver
Forms VLDL (very low density lipoprotein)

Becomes low density LDL by losing triacylglycerols and becomes

bad for you
Apolipoproteins- vesicles for cholesterol
o Outside is hydrophilic and can move out of cell into body
HDL good for as it = clean up crew
Cholesterol synthesis
Starts from cytosolic acetyl CoA
Reduced to fatty acids and cholesterols by NADPH
Step 1

o Acetoacetyl CoA from 2 Acetyl CoA

Thiolase catalyzes this step
Cytosol step
Step 2
o Acetoacetyl CoA + Acetyl CoA to form HMG through HMG CoA
synthase
o Stays in cytoplasm to become mevalonate or goes to
mitochondria to become acetoacetate and acetyl CoA
Step 3
o HMG-CoA reductase- removes CoA and becomes mevalonate
o Uses 2 NADPH
o Rate determining step
o Statins inhibit step
o Competitive inhibitors against HMG CoA
o Big big big, cyclization lalalalalalala
Steps x infinity
o BOOM CHOLESTEROL YAYAYAYAYAYAY

Cholesterol = precursor for steroid hormone synthesis

Cholesterol derivative + UV light vitamin D vut? Just give me a ton of
cholesterol and a UV lamp. Ill be IRON MAN.
Cholesterol metabolism regulation
Too much cholesterol inhibits HMG CoA reductase = de novo
shutdown
Transcriptional control
Hypercholersterolemia (HF)
o Oversynthesize cholesterol (hypercholesterol)
Normal people
o LDL internalized and delivered to ER
o SCAP-SREBP complex
SCAP binds to cholesterol and keeps it in ER when
abundant
SREB DNA-binding sequence cut when cholesterol levels
low
Goes to nucleus and activates HMG-CoA reductase
AMPK

PK complex that senses energy status

Binds AMP to gamma unit

Conformation changes and alpha subunit becomes phosphorylated
by upstream kinases
Active and phosphorylates HMG CoA reductase and ACC
Low energyAMPK activatedphosphorylates ACC/HMG CoA
reductasefatty acid synthesis shut down along w/ cholesterol
synthesis