Fatty Acid Synthesis

Question 1

Mention sources of fatty acid to heart

Answer 1

1. Albumin bound FAs secreted from adipose tissue
2. Circulated TAG-rich lipoproteins
3. De novo FA synthesis occurs to lesser extent in cardiomyocye more in liver.

Question 2

The immediate substrate for FAS is ….., teh immediate product is ….

Answer 2

Acetyl-CoA

Palmitate

Question 3

Mention required units for fatty acid syntehsis

Answer 3

Acetyl CoA, ATP, NADPH+H, Mn++, biotin, bicarbonate.

Question 4

Describe the transport of acetyl CoA outside the mitochondria

Answer 4

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.

Question 5

Mention sources of NADPH

Answer 5

1. HMP
2. Malic enzyme
3. Cytoplasmic isocitrate dehydrogenase

Question 6

Mention the rate-limiting enzyme of FA synthesis and its requirements

Answer 6

Acetyl CoA carboxylase

HCO3 & ATP & biotin

Question 7

Describe composition of fatty acid synthase multienzyme complex

Answer 7

Two identical monomers, each formed of seven subunits having 2 -SH groups one on acyl carrying protein and one on cysteine residue

Question 8

Mention advantages of multienzyme complex

Answer 8

More efficient ( successive active sites more available to intermediates
Less interference of competitive inhibitors

Question 9

Mention enzymes which form acetyl-malonyl enzyme

Answer 9

Acetyl-transacylase enzyme

Malonyl transacykase enzyme

Question 10

Mention the name & action of condensing enzyme

Answer 10

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.

Question 11

Mention the successive steps which occur to ketoacyl, the oroduct formed & coenzyme required

Answer 11

Reduction, dehydration, reduction
Butyryl CoA
NADPH

Question 12

The steps of FA synthesis occur … times, forming ….. , …C

Answer 12

7
Palmitate
16

Question 13

The free palmitate is liberated from eznyme complex by …..

Answer 13

Thioesterase (deacylase)

Question 14

Acetyl CoA primer formes …&…

Answer 14

C15 & C16

Question 15

When …. is used as primer, odd chain number is produced

Answer 15

Propionyl CoA

Question 16

Describe allosteric regulation of FA synthesis

Answer 16

Acetyl CoA carboxylase is inhibited by long-chain fatty acyl CoA & activated by citrate

Question 17

Decsribe covalent modification of Acetyl CoA carboxylase

Answer 17

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

Question 18

Mention fates of activated FA

Answer 18

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

Question 19

….. & …. Are adaptive enzymes

Answer 19

Fatty acid synthase complex

Acetyl CoA carboxylase

Question 20

Mention general modifications of fatty acids

Answer 20

Elongation & desaturation

Question 21

Mention the enzyme of elongation, the unit used & its site

Answer 21

Elongase
Malonyl CoA
Smooth endoplasmic reticulum

Question 22

The first site desaturated usually is …..

Answer 22

Between carbon 9 and 10

Question 23

Mention the requirements of liver desaturases

Answer 23

O2, NADH or NADPH, cytochrome b5, FAD-linked reductase

Question 24

GR: All fatty acids containing a double bond beyond C9 are essential

Answer 24

Since desaturases lack the ability to form double bonds from carbon 10 to the omega-end of the chain.

Question 25

Mention essential fatty acids

Answer 25

Linolenate | Lenoleate

Question 26

The precursor of arachidonic acid is ….

Answer 26

Linoleic acid

Question 27

Give an example of how desaturation and elongation by 2-units alternate

Answer 27

A 6-desaturase produces gamma-linolenic acid from linoleic acid Elongated to eicosatrienoic acid A 5-desaturase then produces arachidonic acid

Question 28

Describe importance of omega-3 fatty acids

Answer 28

Form eicosapentaenoic acid which can form docosahexaenoic acid

Question 29

How does palmitate affect development of heart failure

Answer 29

1. Lipotoxicity: as TAG is increased and accumulated in cytoplasm. 2. Oxidative stress & cellular death: trigger Ca++ efflux from ER to mitochondria causing its swelling & depolarization, uncoupling, loss of ATP. Cytochrome c release & apoptosis.

Question 30

GR: oleate Reduce the risk of CV disease

Answer 30

As their ester bond with cholesterol is easily hydrolysed giving free cholesterol which can be readily excreted or changed into bile.

Question 31

Mention importance of CL

Answer 31

Formation & maintenance of essential inner mitochondrial membrane proteins and respiratory complexes

Question 32

GR: Linoleic acid may contibute to atherosclerosis

Answer 32

It is a precursor arachidonic acid increase production of inflammatory prostanoids which is associated with atherosclerosis.

Question 33

GR: Omega-3 FA are important in protecting against CV death

Answer 33

Their ester bond formation with with glycerol in TAG & cholesterol is easilty hydrolysed thus dec plasma & tissue TAG & cholesterol.

Question 34

The enzyme …. ensures continuous FAs supply for mitochondrial oxidation

Answer 34

HSL

Question 35

Describe fate of glycerol

Answer 35

Shuttled to liver Coverted to glycerol 3-phosphate by glycerol kinase Converted to DHAP via GAP dehydrogenase. Used for glycolysis or gluconeogenesis

Question 36

Describe how cardiac surplus leads to heart failure

Answer 36

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.