Biochemistry - Metabolism - Fat/Cholesterol Flashcards

1
Q

In what form are lipids ingested?

A

Triacylglycerols

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2
Q

What digests lipids in the stomach?

A

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

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3
Q

What signals release of bile to duodenum?

A

CCK

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4
Q

What signals release of bicarb to duodenum?

A

Secretin

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5
Q

What digests TAGs in the duodenums?

A

Pancreatic lipase, removes one fatty acid at a time.

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6
Q

What digests cholesteryl-esters in the duodenum?

A

cholesterol ester hydrolase

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7
Q

How are small chain fatties absorbed by enterocytes?

A

Freely absorbed

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8
Q

How are medium chain fatties absorbed by enterocytes?

A

Freely absorbed

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9
Q

How are long chain fatties absorbed by enterocytes?

A

In bile acid micelles

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10
Q

How is free cholesterol absorbed by enterocytes?

A

in bile acid micelles

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11
Q

What happens to absorbed fatty acids in the enterocyte?

A

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

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12
Q

What is the protein associated with chylomicrons?

A

Apolipoprotein B48

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13
Q

How do chylomicrons pass into lymphatic system?

A

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

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14
Q

Where do chylomicrons enter circulation?

A

Left subclavian vein

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15
Q

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

A

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

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16
Q

What does lipoprotein lipase require?

A

co-enzyme apolipoprotein CII

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17
Q

What are the fates of FFAs?

A
Enter adipose (oxidize for energy, or stored as TAGs)
Enter muscle (oxidize for energy)
Stay in blood w/ albumin
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18
Q

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

A

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.

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19
Q

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

A

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

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20
Q

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

A

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

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21
Q

Do fats cross the BBB?

A

no

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22
Q

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

A

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

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23
Q

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

A

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

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24
Q

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

A

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

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25
Q

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

A

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

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26
Q

What is the function of apoE?

A

Mediates remnant uptake.

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27
Q

Where is apoE expressed?

A

Chylomicrons, chylomicron remnants, VLDL, IDL, HDL

everywhere except LDL

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28
Q

What is the function of apoA-I?

A

Activates LCAT

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29
Q

What is LCAT?

A

Catalyzes esterifcation of cholesterol.

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30
Q

What is CTEP?

A

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

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31
Q

Where is apoA-I expressed?

A

Chylomicron, HDL

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32
Q

What is the function of apoC-II?

A

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

33
Q

Where is apoC-II expressed?

A

Chlyomicrons, VLDL, and HDL

34
Q

What is apoB48?

A

Mediates chylomicron secretion

35
Q

Where is apoB48 expressed?

A

Chylmicrons, chylomicron remnants

36
Q

What the function of B-100?

A

Binds LDL receptor

37
Q

Where is B-100 expressed?

A

VLDL, IDL, LDL

38
Q

What is the function of chylomicrons?

A

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.

39
Q

What is the function of VLDL?

A

Delivers hepatic TGs to peripheral tissue. Secreted by liver.

40
Q

What is the function of IDL?

A

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

41
Q

What is the function of LDL?

A

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.

42
Q

What is the function of HDL?

A

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.

43
Q

What is cholesterol necessary for?

A

Cell membrane integrity
Bile acid synthesis
Steroids
Vitamin D

44
Q

What is the rate limiting step of cholesterol synthesis?

A

HMG-CoA reductase: HMG CoA to mevalonate

45
Q

What is LCAT?

A

esterifies 2/3 of plasma cholesterol

46
Q

What is pancreatic lipase?

A

degradation of dietary triglycerides (TGs) in small intestinte

47
Q

What is lipoprotein lipase?

A

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

48
Q

What is hepatic TG lipase (HL)?

A

Degradation of TGs remaining in IDL

49
Q

What is hormone sensitive lipase?

A

Degradation of TGs stored in adipocytes.

50
Q

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

A

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

51
Q

How does Fatty Acid CoA get inside the mitochondrial membrane?

A

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

52
Q

What negatively regulates Carnitine Acyltransferase I?

A

malonyl CoA

53
Q

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

A

Carnitine Acyltransferase II switches carnitine back to CoA.

54
Q

What enzymes are involved in beta oxidation of fatty acids?

A

Acyl dehydrogenases

55
Q

What length chains do Long-chain Acyl dehydrogenases degrade?

A

12-18

56
Q

What length chains do medium-chain Acyl dehydrogenases degrade?

A

4-12

57
Q

What length chains do short-chain Acyl dehydrogenases degrade?

A

4-6

58
Q

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

A

Peroxisomes.

59
Q

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

A

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.

60
Q

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

A

FADH2, NADH, acetyl CoA

61
Q

What happens to the acetyl CoA that is produced?

A

Can enter TCA in mito.

Liver mitochondria can make ketones

62
Q

What ketones does the liver make?

A

acetoacetate and B-hydroxybutyrate

63
Q

Where can ketones be used?

A

Muscle and brain

64
Q

What runs out in prolonged starvation and diabetic ketoacidosis?

A

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

65
Q

What happens in alcoholism?

A

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

66
Q

Does urine test for ketones detect B-hydroxybutyrate?

A

No

67
Q

Where does fatty acid synthesis occur predominantly?

A

liver, lactating mammary glands, adipose tissue.

68
Q

Under what conditions does fatty acid synthesis occur?

A

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

69
Q

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

A

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

70
Q

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

A

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

71
Q

What happens when citrate diffuses into the cytoplasm?

A

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

72
Q

What is the rate limiting step of fatty acid synthesis?

A

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

73
Q

What does Acetyl CoA carboxylase require?

A

biotin, bicarb, ATP.

74
Q

What activates Acetyl CoA carboxylase?

A

citrate, insulin

75
Q

What is Acetyl CoA carboxylase inhibited by?

A

epi, glucagon, AMP, and palmitoyl CoA.

76
Q

What is the end product of fatty acid synthesis?

A

Palmitate, a 16 C fatty.

77
Q

What must cells have in order to utilize ketones?

A

Mitochondria.

78
Q

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

A

thiophorase: succinylCoA-acetoacetate-CoA transferase