Lipid Metabolism and Disorders Flashcards

1
Q

What are the 3 types of dietary lipids

A

Triglycerides- principally
Cholesterol
Phospholipids

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2
Q

what are the types of dietary fatty acids in triglycerides

A

saturated
monounsaturated
polyunsaturated

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3
Q

where does lipid digestion occur

A

Occurs in small intestine

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4
Q

What role does bile play in lipid digestion

A

Bile is an emulsifier, it turns large droplets into small lipid droplets –> easier digestion

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5
Q

What role do pancreatic lipase and colipase play in lipid digestion

A

Break down TAG into 2 fatty acids and monoglyceride

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6
Q

What is the target of drug Orlistat and what is its function

A

Targets are pancreatic lipase and colipase

Function: drug designed to inhibit lipid digestion

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7
Q

what are the steps of lipid digestion

A

Large lipid droplets converted by bile salts (emulsifiers) into small lipid droplets.
Small lipid droplets are converted by bile salts, pancreatic lipase and colipase into water soluble micelles of Fatty acids and monoglycerides

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8
Q

describe the steps of lipid absorption

A

TRiglycerides (TAG) re-formed in intestinal cell –> TAG packaged with cholesterol, lipoproteins and other lipids to form chylomicrons –> chylomicrons released into lymphatic system by exocytosis

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9
Q

describe the transport of lipids in chylomicron from plasma to adipose tissue

A

PLASMA: TAG are packaged into large molecules known as chylomicron. The enzyme, Lipoprotein lipase breaks down chylomicron into FA.

ADIPOSE: FA travel to adipose tissue where they are broken down to TAG (storage), structural FA (phoshphlipids) and Oxidation (ATP).

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10
Q

Describe the transport of lipids in chylomicron from plasma to liver

A

PLASMA: Large chylomicron molecules become small chylomicron molecules as lipids travel to adipose tissue.

LIVER: small chylomicrons travel to liver and are packaged into VLDL

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11
Q

describe endogenous lipid transport

A

Chylomicrons in liver packaged into VLDL > VLDL travels in capillaries > LPL breaks it down to free fatty acids which is stored in the adipose tissue > LPL attacks VLDL and expresses IDL protein > IDL protein interacts with the liver and is converted into LDL > LDL travels in the plasma > peripheral tissues take up the LDL

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12
Q

What 3 processes can u make from FFA

A

Ketone bodies
Phospholipid synthesis
B-Oxidation (making ATP)

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13
Q

What is B-oxidation

A

generation of energy (ATP) from fatty acids

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14
Q

what is the 1st step of B-oxidation

A

fatty acids added to acetyl CoA to form fatty acyl-CoA (makes it more soluble)

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15
Q

where does B-oxidation occur

A

occurs within the mitochondria

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16
Q

Fatty acids must cross the ____________

A

inner mitochondrial membrane

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17
Q

Describe the function of carnitine

A
  • carrier molecule that transports fatty acids to inner mitochondrial membrane
  • derived from lysine and methionine
  • high percentage in muscle (muslce carries out a lot of B oxidation)
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18
Q

Describe fatty acid entry to mitochondria

A

FACoA converted to FAcarnitine by CPT I (Carnitine Palmitoyl transferase I)

FAcarnitine is then converted to FACoA by CPT II

FACoA enters B oxidation

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19
Q

How does FACoA become Acetyl CoA

A

FACoA degraded by oxidation at the B-carbon.
Reduces size of fatty acid chain by 2 carbons each time
–> Acetyl CoA

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20
Q

What does B-oxidation yield

A

FADH2
NADH
Acetyl CoA

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21
Q

________ are an excellent source of ATP

A

Fatty acids

22
Q

what is triglyceride synthesis

A

esterification of 3 fatty acids and glycerol

23
Q

Describe triglyceride synthesis

A
  • LPL hydrolyses TAG in chylomicrons
  • DGAT re-esterifies to TAG
  • glycerol obtained form glycolysis
24
Q

what is lipolysis and when does it occur

A

Triglyceride breakdown into 3 FA and glycerol

Fasting state

25
Q

what is hormone sensitive lipase and what does it do

A

Found in adipose tissue
Stimulates lipolysis
Activated by camp-dependent phosphorylation in response to adrenaline in fasted state, inhibited by insulin

26
Q

Describe fatty acid synthesis

A

Reverse of B oxidation

Fatty acids built 2 carbons at a time

27
Q

What are the key regulatory enzymes of fatty acid synthesis

A

Acetyl CoA Carboxylase (1st)

Fatty Acid synthase (2nd)

28
Q

what is the function of Acetyl CoA Carboxylase (1st step)

A

Converts Acetyl CoA –> Malonyl CoA

29
Q

what component does Acetyl coA carboxylase require to carry out its function

A

Biotin

30
Q

what is the 2nd step of fatty acid synthesis where fatty acid synthase is involved

A

Acetyl CoA coupled to Malonyl CoA

7 successive steps by multifunctional enzyme- fatty acod synthase

31
Q

where does fatty acid synthesis occur

A

occurs in cytoplasm

32
Q

what does fatty acid syntehsis require

A

requires NADPH (pentose phosphate pathway)

33
Q

how are ketones formed

A

B-oxidation leads to substantial amount of acetyl co A production
Too much Acetyl CoA makes ketones

34
Q

If oxaloacetate not present, then acetyl coA does not go through the TCA cycle and will be converted to _____

A

ketones

35
Q

give examples of ketone bodies

A

Acetoacetate
B-hydroxybutyrate
Acetone

36
Q

Acetacetate can be converted to _____ and _______

A

Acetone

B-hydroxybutyrate

37
Q

Describe formation of phospholipids

A

Diglyceride is made (same steps as Triglyceride)

Then, combined with an alcohol

38
Q

High levels of phospholipid synthesis occurs in what type of cells

A

Rapidly-dividing cells

39
Q

can essential fatty acids be synthesised

A

NO

40
Q

how are essential fatty acids obtained

A

Obtained from diet

41
Q

what are the functions of essential fatty acids

A
  • cell membrane formation
  • required for proper growth and development
  • required for brain and nerve function
42
Q

what are essential fatty acids a precursor of

A
  • Eicosanoids
  • Prostanoids
  • Leukotrienes
43
Q

what does omega-6 fatty acid lower regarding CV risk

A

may lower LDL and HDL

44
Q

What are the key regulators of lipid metabolism

A

Insulin and noradrenaline

45
Q

What effect does insulin have on lipid metabolism

A

INSULIN GETS LIPID TO BE STORED
stimulates FA synthesis, TAG synthesis
suppresses lipolysis

46
Q

what effect does noradrenaline have on lipid metabolism

A

stimulates lipolysis

47
Q

What does insulin stimulate

A
  • GLUT 4 mediated transport of glucose
  • ACC activity- acetyl choline carboxylase
  • Increases expression of FAS
  • Increases activity of LPL in adipose (Increased uptake of lipids from circulating TGs)

active in fed state- stimulating storage

48
Q

what does noradrenaline stimulate

A
  • cAMP synthesis
  • cAMP dependent (PKA) activation
  • PKA mediated phosphorylation and activation of HSL

Goal: stimulate hormone sensitive lipase to breakdown TG stores

active in fasted state

49
Q

How does insulin inhibits lipolysis

A

Doesnt inhibit lipolysis directly

Insulin stimulates breakdown of cAMP- inhibition of activation of hormone sensitive lipase

50
Q

How does the regulation of LPL by insulin differ in muscles and adipocytes in fed and fasted state

A

FED state:

  • Adipocytes: LPL synthesis increase
  • Muscle: LPL synthesis decrease

FASTED state:

  • Adipocytes: LPL synthesis decrease
  • Muscle: LPL synthesis increase