Biochemistry - Metabolism - Fat/Cholesterol

Question 1

In what form are lipids ingested?

Answer 1

Triacylglycerols

Question 2

What digests lipids in the stomach?

Answer 2

Lingual lipase and Gastric lipase digest short and medium chains.
These are the ones in milk lipids - impt in pts w/ pancreatic insufficiency.

Question 3

What signals release of bile to duodenum?

Answer 3

CCK

Question 4

What signals release of bicarb to duodenum?

Answer 4

Secretin

Question 5

What digests TAGs in the duodenums?

Answer 5

Pancreatic lipase, removes one fatty acid at a time.

Question 6

What digests cholesteryl-esters in the duodenum?

Answer 6

cholesterol ester hydrolase

Question 7

How are small chain fatties absorbed by enterocytes?

Answer 7

Freely absorbed

Question 8

How are medium chain fatties absorbed by enterocytes?

Answer 8

Freely absorbed

Question 9

How are long chain fatties absorbed by enterocytes?

Answer 9

In bile acid micelles

Question 10

How is free cholesterol absorbed by enterocytes?

Answer 10

in bile acid micelles

Question 11

What happens to absorbed fatty acids in the enterocyte?

Answer 11

Rebuilt into TAGs by Acyl Coa Synthetase and packaged into chylomicrons.

Question 12

What is the protein associated with chylomicrons?

Answer 12

Apolipoprotein B48

Question 13

How do chylomicrons pass into lymphatic system?

Answer 13

ER –> Golgi –> exocytosis to lacteals –> lymph

Question 14

Where do chylomicrons enter circulation?

Answer 14

Left subclavian vein

Question 15

How are chylomicrons picked up in capillaries of skeletal muscle and adipose tissue?

Answer 15

Lipoprotein Lipase from muscle and adipose, expressed in endothelial layer of capillary beds.

Question 16

What does lipoprotein lipase require?

Answer 16

co-enzyme apolipoprotein CII

Question 17

What are the fates of FFAs?

Answer 17

Enter adipose (oxidize for energy, or stored as TAGs)
Enter muscle (oxidize for energy)
Stay in blood w/ albumin

Question 18

What are the fates of glycerol? What enzyme does this organ have?

Answer 18

Goes to liver, where glycerol-3-phosphate can be used for glycolysis or gluconeogenesis. Only liver can use glycerol-3-phosphate for gluconeogensis or glycolysis due to enzyme glycerol kinase –> makes it DHAP.

Question 19

What are the fates of the remnant chylomicrons in the blood?

Answer 19

Taken up by liver - bind to receptors and endocytosed. Requires apoE.

Question 20

What kind of tissue uses fatty acid as primary energy source?

Answer 20

Mito-rich tissues. Slow twitch muscle fibers rely primarily on fatty acid oxidation as energy source

Question 21

Do fats cross the BBB?

Answer 21

no

Question 22

During prolonged fasting, why does liver/tissue use fatty aicds?

Answer 22

During prolonged fasting, liver and other tissues oxidize fatty acids in order to conserve glucose for the brain.

Question 23

How does the energy from a fatty acid compare to the energy from a molecule of gluocse?

Answer 23

Way more. 16 carbons in palmitic acid –> 130 ATP.

Question 24

When there is high degree of insulin, what happens to fattys?

Answer 24

At high I/G, dietary TAGs circulating are taken up by LPLs and oxidized for energy.

Question 25

When there is a low degree of insulin, what happens to fattys?

Answer 25

At low I/G, TAGs stored in adipose are released and degraded to FFAs, bound to albumin --> circulate to tissue.

Question 26

What is the function of apoE?

Answer 26

Mediates remnant uptake.

Question 27

Where is apoE expressed?

Answer 27

Chylomicrons, chylomicron remnants, VLDL, IDL, HDL | everywhere except LDL

Question 28

What is the function of apoA-I?

Answer 28

Activates LCAT

Question 29

What is LCAT?

Answer 29

Catalyzes esterifcation of cholesterol.

Question 30

What is CTEP?

Answer 30

Cholesterol ester transfer protein - mediates transfer of cholesterol esters to other lipoprotein particles

Question 31

Where is apoA-I expressed?

Answer 31

Chylomicron, HDL

Question 32

What is the function of apoC-II?

Answer 32

Lipoprotein lipase cofactor - necessary for peripheral degradation of TGs in chylomicrons and VLDLs.

Question 33

Where is apoC-II expressed?

Answer 33

Chlyomicrons, VLDL, and HDL

Question 34

What is apoB48?

Answer 34

Mediates chylomicron secretion

Question 35

Where is apoB48 expressed?

Answer 35

Chylmicrons, chylomicron remnants

Question 36

What the function of B-100?

Answer 36

Binds LDL receptor

Question 37

Where is B-100 expressed?

Answer 37

VLDL, IDL, LDL

Question 38

What is the function of chylomicrons?

Answer 38

Delivers dietary TGs to peripheral tissue. Delivers cholesterol to liver in the form of chylomicron remnants, which are mostly depleted of their TGs. Secreted by intestinal epithelial cells.

Question 39

What is the function of VLDL?

Answer 39

Delivers hepatic TGs to peripheral tissue. Secreted by liver.

Question 40

What is the function of IDL?

Answer 40

Formed in the degradation of VLDL. Delivers TGs and cholesterol to liver.

Question 41

What is the function of LDL?

Answer 41

Delivers hepatic cholesterol to peripheral tissues. Formed by hepatic lipase modification of IDL in the peripheral tissue. Taken up by target cells via receptor-mediated endocytosis.

Question 42

What is the function of HDL?

Answer 42

Mediates reverse cholesterol transport from periphery to liver. Acts as a repository for apolipoproteins C and E (which are needed for chylomicron and VLDL metabolism). Secreted from both liver and intestine. Alcohol incr synthesis.

Question 43

What is cholesterol necessary for?

Answer 43

Cell membrane integrity Bile acid synthesis Steroids Vitamin D

Question 44

What is the rate limiting step of cholesterol synthesis?

Answer 44

HMG-CoA reductase: HMG CoA to mevalonate

Question 45

What is LCAT?

Answer 45

esterifies 2/3 of plasma cholesterol

Question 46

What is pancreatic lipase?

Answer 46

degradation of dietary triglycerides (TGs) in small intestinte

Question 47

What is lipoprotein lipase?

Answer 47

LPL - degradation of TGs circulating in chylomicrons and VLDLs. Found on vascular endothelial surface.

Question 48

What is hepatic TG lipase (HL)?

Answer 48

Degradation of TGs remaining in IDL

Question 49

What is hormone sensitive lipase?

Answer 49

Degradation of TGs stored in adipocytes.

Question 50

Once fatty acids enter cell, how are they trapped within it?

Answer 50

Fatty acid CoA synthase adds a CoA; becomes Fatty-Acyl-CoA

Question 51

How does Fatty Acid CoA get inside the mitochondrial membrane?

Answer 51

Carnitine shuttle - CoA replaced with carnitine by Carnitine Acyltransferase I - Rate limiting step! Carnitine translocates, brings into mito on inner membrane. *Only long chains?

Question 52

What negatively regulates Carnitine Acyltransferase I?

Answer 52

malonyl CoA

Question 53

Once inside the mitro, what happens to fatty+carntine?

Answer 53

Carnitine Acyltransferase II switches carnitine back to CoA.

Question 54

What enzymes are involved in beta oxidation of fatty acids?

Answer 54

Acyl dehydrogenases

Question 55

What length chains do Long-chain Acyl dehydrogenases degrade?

Answer 55

12-18

Question 56

What length chains do medium-chain Acyl dehydrogenases degrade?

Answer 56

4-12

Question 57

What length chains do short-chain Acyl dehydrogenases degrade?

Answer 57

4-6

Question 58

Where are very long chains (20-26) degraded?

Answer 58

Peroxisomes.

Question 59

What do the Acyl dehydrogenases do? What happens w/ odd-numbered chains?

Answer 59

Shortens fatty acyl chains 2 carbons at a time. Odd #rd chains are left w/ propionyl CoA, which gets converted to methylmalonyl CoA and then succinyl CoA which can enter TCA.

Question 60

What is generated from the breakdown of fatty acyl-CoAs?

Answer 60

FADH2, NADH, acetyl CoA

Question 61

What happens to the acetyl CoA that is produced?

Answer 61

Can enter TCA in mito. | Liver mitochondria can make ketones

Question 62

What ketones does the liver make?

Answer 62

acetoacetate and B-hydroxybutyrate

Question 63

Where can ketones be used?

Answer 63

Muscle and brain

Question 64

What runs out in prolonged starvation and diabetic ketoacidosis?

Answer 64

Oxaloacetate depleted for gluconeogensis; pyruvate converted to acetylCoA. --> ketones

Question 65

What happens in alcoholism?

Answer 65

NADH excess shunts oxaloacetate to malate. Causes excess of acetyl CoA. --> ketones

Question 66

Does urine test for ketones detect B-hydroxybutyrate?

Answer 66

No

Question 67

Where does fatty acid synthesis occur predominantly?

Answer 67

liver, lactating mammary glands, adipose tissue.

Question 68

Under what conditions does fatty acid synthesis occur?

Answer 68

Glucose influx from gut, glucose not deposited as glycogen converted to fat in the liver.

Question 69

What is the first step of fatty acid synthesis from incoming glucose?

Answer 69

Conversion of glucose to acetyl CoA via glycolysis and pyruvate dehydrogenase.

Question 70

When ATP is high, in what form do metabolites downstream from acetyl CoA in the TCA accumulate?

Answer 70

Citrate. (isocitrate dehydrogenase is negatively regulated by high ATP).

Question 71

What happens when citrate diffuses into the cytoplasm?

Answer 71

Cleaved by ATP-citrate-lysase, becomes oxaloacetate and acetyl CoA.

Question 72

What is the rate limiting step of fatty acid synthesis?

Answer 72

Acetyl-CoA carboxylase, which converts Acetyl CoA to malonyl CoA.

Question 73

What does Acetyl CoA carboxylase require?

Answer 73

biotin, bicarb, ATP.

Question 74

What activates Acetyl CoA carboxylase?

Answer 74

citrate, insulin

Question 75

What is Acetyl CoA carboxylase inhibited by?

Answer 75

epi, glucagon, AMP, and palmitoyl CoA.

Question 76

What is the end product of fatty acid synthesis?

Answer 76

Palmitate, a 16 C fatty.

Question 77

What must cells have in order to utilize ketones?

Answer 77

Mitochondria.

Question 78

What enzyme does the liver lack that prevents it from using ketones as a source of energy?

Answer 78

thiophorase: succinylCoA-acetoacetate-CoA transferase