Fatty Acid Synthesis Flashcards
Mention sources of fatty acid to heart
- Albumin bound FAs secreted from adipose tissue
- Circulated TAG-rich lipoproteins
- De novo FA synthesis occurs to lesser extent in cardiomyocye more in liver.
The immediate substrate for FAS is ….., teh immediate product is ….
Acetyl-CoA
Palmitate
Mention required units for fatty acid syntehsis
Acetyl CoA, ATP, NADPH+H, Mn++, biotin, bicarbonate.
Describe the transport of acetyl CoA outside the mitochondria
Condesed with oxaloacetate to citrate synthase. Citrate is transported by special transporter to cytosol. Then broken down in cytosol to acetyl CoA & oxaloacetate by ATP- citrate lyase.
Mention sources of NADPH
- HMP
- Malic enzyme
- Cytoplasmic isocitrate dehydrogenase
Mention the rate-limiting enzyme of FA synthesis and its requirements
Acetyl CoA carboxylase
HCO3 & ATP & biotin
Describe composition of fatty acid synthase multienzyme complex
Two identical monomers, each formed of seven subunits having 2 -SH groups one on acyl carrying protein and one on cysteine residue
Mention advantages of multienzyme complex
More efficient ( successive active sites more available to intermediates Less interference of competitive inhibitors
Mention enzymes which form acetyl-malonyl enzyme
Acetyl-transacylase enzyme
Malonyl transacykase enzyme
Mention the name & action of condensing enzyme
3-ketoacyl synthase
Condenses acetyl group on cysteine with malonyl group on APC forming 3-ketoacyl enzyme with liberation of CO2 so reaction is in one direction. So SH of Cyst is free.
Mention the successive steps which occur to ketoacyl, the oroduct formed & coenzyme required
Reduction, dehydration, reduction
Butyryl CoA
NADPH
The steps of FA synthesis occur … times, forming ….. , …C
7
Palmitate
16
The free palmitate is liberated from eznyme complex by …..
Thioesterase (deacylase)
Acetyl CoA primer formes …&…
C15 & C16
When …. is used as primer, odd chain number is produced
Propionyl CoA
Describe allosteric regulation of FA synthesis
Acetyl CoA carboxylase is inhibited by long-chain fatty acyl CoA & activated by citrate
Decsribe covalent modification of Acetyl CoA carboxylase
Inactivated by phosphrylation in presence of glucagon & epinepherine by cAMP dependent kinase & AMO activated protein kinase.
Activated by dephosphorylation in presence of insulin by phosphatase
Mention fates of activated FA
Delivered to mitochondria & oxidised
Exterification to gycerol 3P then TAG, to cholesterol forming cholesterol ester
Phospholilids (structural fatty acids)
Arachidonic acid serve as precusor if biologically active eicosanoid
….. & …. Are adaptive enzymes
Fatty acid synthase complex
Acetyl CoA carboxylase
Mention general modifications of fatty acids
Elongation & desaturation
Mention the enzyme of elongation, the unit used & its site
Elongase
Malonyl CoA
Smooth endoplasmic reticulum
The first site desaturated usually is …..
Between carbon 9 and 10
Mention the requirements of liver desaturases
O2, NADH or NADPH, cytochrome b5, FAD-linked reductase
GR: All fatty acids containing a double bond beyond C9 are essential
Since desaturases lack the ability to form double bonds from carbon 10 to the omega-end of the chain.
Mention essential fatty acids
Linolenate
Lenoleate
The precursor of arachidonic acid is ….
Linoleic acid
Give an example of how desaturation and elongation by 2-units alternate
A 6-desaturase produces gamma-linolenic acid from linoleic acid
Elongated to eicosatrienoic acid
A 5-desaturase then produces arachidonic acid
Describe importance of omega-3 fatty acids
Form eicosapentaenoic acid which can form docosahexaenoic acid
How does palmitate affect development of heart failure
- Lipotoxicity: as TAG is increased and accumulated in cytoplasm.
- Oxidative stress & cellular death: trigger Ca++ efflux from ER to mitochondria causing its swelling & depolarization, uncoupling, loss of ATP. Cytochrome c release & apoptosis.
GR: oleate Reduce the risk of CV disease
As their ester bond with cholesterol is easily hydrolysed giving free cholesterol which can be readily excreted or changed into bile.
Mention importance of CL
Formation & maintenance of essential inner mitochondrial membrane proteins and respiratory complexes
GR: Linoleic acid may contibute to atherosclerosis
It is a precursor arachidonic acid increase production of inflammatory prostanoids which is associated with atherosclerosis.
GR: Omega-3 FA are important in protecting against CV death
Their ester bond formation with with glycerol in TAG & cholesterol is easilty hydrolysed thus dec plasma & tissue TAG & cholesterol.
The enzyme …. ensures continuous FAs supply for mitochondrial oxidation
HSL
Describe fate of glycerol
Shuttled to liver
Coverted to glycerol 3-phosphate by glycerol kinase
Converted to DHAP via GAP dehydrogenase. Used for glycolysis or gluconeogenesis
Describe how cardiac surplus leads to heart failure
Cardiac surplus — overexpression of lipogenic transcription factors — overexpression of FA synthase — increased lipogenesis — ectopic lipid deposition myocardium —hampers myocardial function due to mechanical effect and causes nonoxidative/oxidative cardiomyocyte death. This all causes heart dysfunction.
