Lecture 49

Question 1

de novo synthesis

Answer 1

synthesis starting from small intermediates (scraps) to build a bigger molecule

pg 1258

Question 2

FA and lipid synthesis de novo

Answer 2

• liver decides when to convert one substance to another and where to send it
• C16 (palmitate) is only lipid made from fatty acid synthesis, but it can be modified before leaving the liver
• palmitoyl CoA (C16) -> product of FA synthesis -> activated palmitate
• acetyl CoA (accumulates when energy is plentiful) cannot pass through mitochondrial membrane so converted to citrate which can and then converted back once in cytosol

pg 1260

Question 3

fatty acid synthesis: transport across mitochondria

Answer 3

• step 1
• oxaloacetate and acetyl CoA combine using citrate synthase (condensation rxn) to form citrate and release CoA
• citrate transported across mitochondria
• citrate uses ATP citrate lyase, CoA, water, and ATP to reform oxaloacetate and acetyl CoA

pg 1261, 1263

Question 4

TCA cycle summary of regulation review

Answer 4

citrate formed in TCA cycle from acetyl CoA using citrate synthase; this can exit the mitochondria

pg 1262

Question 5

fatty acid synthesis: activation of ACC

Answer 5

• step 2: acetyl CoA carboxylase (ACC)
• rate-limiting and regulated step in FA synthesis
• requires ATP and biotin (vitamin B7, required for all carboxylases as it donates CO₂)
• inactive enzyme exists as inactive protomers
• activated by citrate in cytosol for arrangement into active polymer
• converts acetyl CoA to malonyl CoA by adding a CO₂ group using ATP

pg 1264

Question 6

regulation of LCFA degradation review

Answer 6

malonyl CoA inhibits entry of fatty acids into mitochondria therefore preventing β-oxidation

pg 1265

Question 7

acetyl CoA carboxylase regulation

Answer 7

• allosteric regulation
• activator: forms active polymer in presence of citrate
• inhibitor: feedback inhibition by end product palmitoyl CoA
• covalent modifications: phosphorylation/dephosphorylation

pg 1266

Question 8

covalent modifications of acetyl CoA carboxylase

Answer 8

• ACC inactive when phosphorylated, ACC activated when dephosphorylated
• AMP-activated protein kinase inactivates ACC by phosphorylation to stop anabolic pathway when energy is low

pg 1267

Question 9

fatty acid synthesis: multistep synthesis of palmitate

Answer 9

chemical opposite of β-oxidation -> 3rd step of FA synthesis

1. condensation
2. reduction #1
3. dehydration
4. reduction #2

repeated until a 16 carbon, saturated fatty acid is formed (palmitate) and released in a hydrolysis reaction

pg 1268-1269

Question 10

fatty acid synthesis: elongation and desaturation

Answer 10

• 4th step of FA synthesis
• palmitate is elongated or desaturated using enzymes to form other fatty acids
• no double bonds can be formed beyond position 9 in the human body
• fatty acids use fatty acyl CoA synthetase to form fatty acyl CoA which can lead to triacylglycerols, phospholipids, cholesterol esters, and sphingolipids

pg 1270

Question 11

fatty acid synthesis vs degradation

Answer 11

• greatest flux through pathway: after carb-rich meal VS in starvation
• hormonal state favoring pathway: high insulin/glucagon ratio VS low
• major tissue site: liver VS muscle (exercise), liver
• subcellular location: cytosol VS mitochondria (compartmentalization)
• activator: citrate VS none
• inhibitor: palmitoyl CoA vs malonyl CoA
• product: palmitate vs acetyl CoA

pg 1271

Question 12

synthesis of TAG: lipogenesis

Answer 12

• glycerol-3-P to lysphosphastidic acid via acyltransferase using fatty acyl-CoA-1
• lysphosphastidic acid to phosphatidic acid (DAG phosphate) via acyltransferase using fatty acyl-CoA-2
• phosphatidic acid (DAG phosphate) to diacylglycerol (DAG, a 2nd messenger) via phosphatase using water
• DAG to triacylglycerol (TAG) via DAG acyltransferase using fatty acyl-CoA-3

pg 1273

Question 13

synthesis of TAG and glycerol-3-P

Answer 13

• in liver: glycerol from diet transformed to glycerol-3-phosphate in the liver using glycerol kinase; glycerol-3-phosphate can also be formed from a glycolysis pathway
• in adipocyte: not active during fasting because GLUT4 transporter requires insulin, NO kinase so glycerol-3-P only from glycolysis

pg 1274-1275

Question 14

storage and transport of TAG

Answer 14

• TAGs stored in liver, incorporated into VLDL and secreted in the circulation
• TAGs accumulate in intracellular lipid droplets in other tissues
• VLDLs are transported to adipose tissue

pg 1276

Question 15

fate of liver-produced TAG

Answer 15

TAG produced in the liver are incorporated into VLDLs and transported into the blood stream

pg 1277

Question 16

lipogenesis

Answer 16

synthesis of TAG from glucose or non-lipid precursors

pg 1279

Question 17

low fat diet

Answer 17

ineffective at lowering plasma lipids because of acetyl-CoA coming from carbohydrates

pg 1279

Question 18

regulation of lipolysis and release of FAs

Answer 18

low insulin/glucagon ratio and elevated epinephrine:

• activated lipolysis via cAMP and PKA
• activated TAG degradation and FA release into the blood

pg 1281

Question 18

carbs and lipids crosstalk in the liver

Answer 18

• glucose -> glucose-6-P -> pentose phosphate pathway (PPP)
• PPP releases NADPH
• glucose eventually forms pyruvate which goes to TCA cycle to form acetyl CoA and citrate
• citrate in cytosol becomes oxaloacetate and acetyl CoA
• oxaloacetate becomes malate -> malate conversion to pyruvate releases NADPH
• acetyl CoA converted to malonyl CoA which is utilized in fatty acid synthesis

pg 1279