Lipid Metabolism

Question 1

Fed vs fasted state lipid metabolism

Answer 1

Fed state: insulin drives the synthesis of cholesterol and fatty acyl-CoA. FA transported as part

Fasted state: epinephrine drive sythesis of acetyl-CoA from fatty acids. FA transported bound to albumin.

Question 2

Rate limiting enzyme in in fatty acid biosynthesis

Answer 2

acetyl-CoA carboxylase.

Question 3

Acetyl-CoA carboxylase

Answer 3

rate limiting enzyme in fatty acid biosynthesis

catalyzes the formation of malonyl CoArom Acetyl-CoA

cofactor is biotin and serves as the carrier of activated CO2

Question 4

Requirements of fatty acid biosynthesis

Answer 4

1) acetyl groups must be transported from the mitochondria into the cytoplasm. Citrate is the carrier, it also activates acetyl-CoA carboxylase
2) Fatty acid synthase complex. utilizes 1 acetyl coA and 7 malonyl-CoA to synthesize even numbered saturated fatty acids
3) NADPH- generated by PPP.and the cytoplasmic reaction of malate to pyruvate.
4) Biotin- carrier of activated CO2

Question 5

Citrate

Answer 5

stimulates fatty acids synthesis

transports acetyl groups from the mitochondria

allosterically activates acetyl-CoA carboxylase

Question 6

citrate shuttle

Answer 6

pyruvate from glycolysis goes to the mitochondria. oxaloacetate and acetyl coA is generated. Both are converted to citrate so they can be transported to the cytoplasm.

the cytoplasmic citrate can be converted to oxaloacetate, and back to pyruvate to enter the mito again; or it can be converted to AcCoA and participate in fatty acid synthesis

Question 7

Short term regulation of Acetyl CoA carboxylase

Answer 7

• this reaction is irreversible *
  promoters: citrate, insulin, biotin
  inhibitors: palmitoyl CoA, glucagon, epi, AMP

Question 8

Malonyl CoA

Answer 8

product of the reaction catalyzed by AcCoA carboxylase

only physiological inhibitor of Carnatine palmitoyl transferase-1

key regulator of fatty acid oxidation and ketone body formation. reduction in malonyl CoA increaes fatty acid oxidation.

Question 9

Long term regulation of AcCoA carboxylase

Answer 9

increased enzyme synth: high carb diet, insulin, thyroid hormone, fat free diet

Decreased enzyme synth: high fat diet (via low insulin and high glucagon), fasting, glucagon

Question 10

Fatty acid synthase complex (FAS)

Answer 10

catalyzes the formation of fatty acids from:

1 acetyl CoA + 7 malonyl CoA

catylyzes 7 reaction cycles

Question 11

Stochiometry of the FAS reaction

Answer 11

AcCoA (2C) + 7 malonyl CoA (21C) → palmitate (16C) + 7CO2 + 14NAD+ + 8CoA +6H2O

Question 12

Short term regulation of FAS

Answer 12

allosteric activator: fructose 1,6 BP

Question 13

Long term regulation of FAS

Answer 13

increased enzyme synth: high carb diet via insulin, fat free diet

decreased enzyme synthesis: glucagon, high fat diet via low insulin and high glucagon, fasting

Question 14

Essential fatty acids

Answer 14

linoleate and alpha linolenate

omega -3

Question 15

why can’t mamals synthesize linoleic acid?

Answer 15

Cannot synthesize double bonds in fatty acids beyond carbons 9 and 10

Question 16

What happens to TAGs after they are synthesized in the liver?

Answer 16

get packaged into VLDLs.

dietary TAGs are put into chylomicrons in the intestines