Lecture 13 Flashcards
Lipid Anabolism is ___ and where occurs
building up FA, basically the opposite of β oxidation happens in the cytosol
Key intermediate in lipid anabolism (rate limiting step in FA synth)
Malonyl-CoA it is the rate limiting step in FA synthesis
Maonyl-CoA
Malonyl-coa synthesis
Basically carboxylating Acetyl-coa
biotin + HCO3- + ATP → ADP + Pi + modified biotin w/ CO2 → then we add Acetyl-CoA ⇒ malonyl-CoA
Synthetase
has a T to it always uses ATP or ADP
Synthase
no T so it doesn’t use ATP or ADP
Overview of lipid anabolism
- transport Ac-CoA from mitochondria to cytosol
- sythesis of malonyl-coa
- elongation (malonyl-coa pathway)
- condensation step
- reduction step
- deydration
- another reduction
during condesation of malonyl coa synthesis ____ comes off as water, not CO2
the double bond O
Fattty acid synthesis done in
the liver
Fatty acid synthase complex
enzyme does all four rxns to build FA
condensation, reduction, dehydration, reduction
2 landings with Sulfur (function like CoA)
Acyl carrier protein function
Built in to FA complex:
carries acyl groups by thioester linkage
very similar to Co-Ash, they both have pantothenic acid
Acetyl CoA carboxylase is mainly
- carboxylating Acetyl-CoA
- a biotin dependent carboxylation
- & spends ATP
ACC
Substrates
Cofactors
Products
Acetyl-CoA carboxylase
Subs: Biotin + HCO3 + ATP
Cofactors: biotin
Prod: Maolonyl CoA
ACP
Acyl Carrier Protein in E. coli
similar to CoA
Where in the cell does anabolic rxn occur?
cytosol
NADPH sources
malic enzyme
pentose phosphate pathway
main way to get NADPH is
pentose phosphate patway
FAS in bacteria
7 activities in 7 separate polypeptides
FAS in mammals
7 activities in one large polypeptide
Main carbon source for anabolism (provides the building blocks)
Citrate!
when it is abundant it leaves the mitochondria → cytosol and gets cleaved into OAA and Acetyl-CoA which are used in anabolism
Minor source of NADPH for anabolism
Malate
malic enzyme takes malate → Pyr (which is used to make more NADPH)
____ is an allosteric inhibitor of carnitine Palmitoyl-CoA
malonyl-CoA
____ will activate FAS through malonyl-coa
Citrate
hormonal regulation of FAS
glucagon, epinephrine, block synthesis and increase degredation of FA
Fatty acid synthesis location in the cell
cytosol
Fatty acid oxidation location in the cell
AKA ß oxidation
matrix
Key rxns to modify FA
elongation and desaturation
essential FA that we must consume
omega 3 FA
Omega 6 FA
complex polyunsaturated
Made by plants, which we consume and use for other things
Linoleate
Essential FA made by plants only
arachidonate
Derived from linoleate–an omega-6
precursor for important molecules: COX
arachidonic acid are oxidizer molec that make
physiologcal regulatiors:
prostaglandins & thromboxanes
respponsible for controling inflamation, smooth muscle contraction, uterine function, gastric function…
prostaglandins and thromboxanes—super responsive
COX
cycloxigenase
Aspirin covalently bonds to ____ of COX
serine part of COX
covalent inhibitor or COX
aspirin
prostaglandins are
chemicals that promote inflamation, pain and fever
NSAID’s
Non-Steroidal Anti- Inflamatory Drugs
acetominophen
aspirin
ibuprofen
naproxen
isozymes meaning
two differnet versions of an enzyme, encoded from different genes.
have a common ancestor
involved in normal gastric function
COX 1
involved in inflamation and fever
COX 2
why does taking antiinflamatory does cause gastric bleeding?
becuase if enough drug (which should inhibit COX2) is taken, it also starts inhibiting COX1 causing bleeding.
COX-2 specific inhibitions
colecoxib
rofecoxib
Vioxx
a COX2 specific inhibitor (rofecoxib) that causes rare cardiac problems.
the drug that Merck made
“on pathway, off pathway”
inhibiting one thing can inhibit other things in the way
Isoprenes
branched lipid structure used to make sterols
(eg: cholesterol)
basic Isoprene structure
HMG-CoA
4 stages in cholesterol synthesis
- mevalonate production
- conversion to active isoprenes
- condensation of isoprenes, conversion to squalene
- conversion to cholesterol
Mevalonate production rxns
acetyl-coa → acetoacetyl-coa → HMG-CoA → mevalonate
mevalonate production occurs where
cytosol
competivie inhibitors of HMG-CoA reductase
statins
they are rate limiting enzyme for cholesterol synthesis
commitment step of making isoprenes
synth of mevalonate
low density lipoprotein
LDL:
a way to send insoluble things into bloodsteam (which is basically water)
