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Clinical Chemistry 2 > Lipid Advanced Metabolism > Flashcards

Lipid Advanced Metabolism Flashcards

1
Q

Endogenous lipid comes from where?

A

Within the body

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2
Q

Exogenous lipids come from where?

A

Outside the body through the diet e.g. burgers n pizz

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3
Q

Define Lipid

A

A biological substance that is insoluble in water but soluble in organic solvents such as alcohol, chloroform, ether, and acetone. Some phospholipids are not soluble in acetone & some have limited solubility in H2O.

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4
Q

What does the body use lipids for in terms of nutrition?

A

Primary source of fuel for the body

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5
Q

What is the significance of lipids to structure of cells?

A
  • Gives cell membrane stability and rigidity
    *Allow for transmembrane transport of important molecules
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6
Q

What kind of hormones have lipids

A

Steroid hormones such as… vitamin D, cortisol, and aldosterone.

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7
Q

What kind of fat produces heat?

A

Brown. Fat

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8
Q

What is the fat surrounding nerves and help conduct signals in the neuron?

A

Myelin sheet

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9
Q

List major lipids

A

*Free fatty acids
*Phospholipids
*Cholesterol (free & esterified)
*Triglycerides
*Glycolipids
*Prostaglandins

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10
Q

What are triglycerides made up of?

A

Glycerol esters combined with free fatty acids. Refer to Major lipid slide

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11
Q

What kind of fatty acid has no double bonds?

A

Saturated fatty acids

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12
Q

What kind of fatty acid has one double bond?

A

mono-unsaturated fatty acid

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13
Q

What fatty acid has 2 or more double bonds?

A

Polyunsaturated fatty acid

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14
Q

what’s the range of carbons for a short chain FA?

A

4 - 6 carbon atoms

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15
Q

What’s the carbon range for a medium - chain FA?

A

8 - 12 carbon atoms

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16
Q

What’s the carbon range for a long chain FA?

A

12 + carbon atoms

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17
Q

Complete the phrase; _____ are essential component of cell membranes.

A

Phospholipids

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18
Q

What acts as a detergent in clearing other fats out of the body?

A

Phospholipids

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19
Q

What is the term to describe a molecule that has a hydrophilic and hydrophobic structure?

A

Amphiphilic structure

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20
Q

Cis versus Trans fatty acids?

A
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21
Q

Where are phospholipids synthesized?

A

Liver & intestinal epithelium

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22
Q

What are three kinds of important phospholipids?

A
  • Lecithin (phosphatidyl choline)
  • Cephalins (phosphorylated ethanolamine, inositol, and serine)
  • Spingomyelin (spingolipid)
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23
Q

Cholesterol has a ______ ring with side chain of carbon atoms.

A

Perhydrocyclophenanthrone ring with side chain of carbon atoms

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24
Q

Cholesterol (endogenous) is made from what?

A

Acetyl - CoA

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25
Q

What is the product of the enzyme aceto acetyl CoA synthetase?

A

Aceto acetyl CoA

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26
Q

What is the product of HMG - CoA Synthetase?

A

HMG - COA important for cholesterol or ketogenesis

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27
Q

What is the rate limiting enzyme in cholesterol synthesis?

A

HMG - CoA Reductase, a build up of HMG CoA will suggest a defect in HMG CoA reductase.

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28
Q

What are the important functions of cholesterol? (Name 4)

A
  1. Manufacture & repair of cell membrane
  2. Synthesis of Bile acids
  3. Synthesis of Vitamin D (steroid hormone)
  4. Precursor of five major classes of steroid hormone (Progestins, glucocorticoids, mineralocorticoids, androgen, and estrogen)
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29
Q

What are the five major classes of steroid hormones?

A
  1. Progestins
  2. glucocorticoids
  3. mineralocorticoids
  4. androgen
  5. estrogen
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30
Q

Surplus cholesterol goes where?

A

Into the bile acid synthesis pathway to help digest fat (turns fat into droplets)

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31
Q

Where is endogenous cholesterol made in the body?

A

The liver

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32
Q

What is the purpose of LCAT, lecithin cholesterol acyltransferase?

A

Trasnfer FA from Carbon 2 of phosphatidylcholin to cholesterol

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33
Q

If there is a deficiency with LCAT, lecithin cholesterol acyltransferase, what will we see?

A

Elevated levels of cholesterol

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34
Q

LCAT, lecithin cholesterol acyltransferase is bound to what protein?

A

Lipoprotein (HDL)

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35
Q

Acyl - CoA : cholesterol acyltransferase (ACAT) does what?

A

Catalyzes the formation of CoA and cholesterol ester

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36
Q

A person with high cholesterol is at risk for what?

A

Cardiovascular disease

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37
Q

Where does esterification of cholesterol by LCAT take place?

A

Plasma

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38
Q

Hydrolysis of cholesterol takes place where?

A

Liver

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39
Q

What fat is considered majority of neutral fats?

A

Triglycerides

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40
Q

What is triglycerides made of?

A

A glycerol ester + 3 Fatty acids

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41
Q

Triglycerides are a main storage form of _____?

A

Fats

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42
Q

Stored triglycerides can be catabolized into what during fasting or between meals?

A

Free fatty acids

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43
Q

Where do plasma triglycerides come from?

A

Intestine and liver

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44
Q

Intestinal triglycerides come from where?

A

Dietary fat

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45
Q

What organ is the manufacturer of plasma triglycerides?

A

Liver

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46
Q

If a patient requires a lipid profile what do they need to do?

A

Fast for about 12 hours

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47
Q

Cerebroside contains what?

A

Ceramide with a sugar at the 1 - OH moiety.

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48
Q

Glycolipids include two other groups. What are they?

A

Gangliosides and membrane glycosphingolipids

49
Q

This glycolipid lipid is important for cell recognition. What is it?

A

Membrane glycosphingolipids

50
Q

What is the major membrane lipid of CNS called?

A

Gangliosides

51
Q

Describe the prostaglandin structure.

A

Long chain polyunsaturated FA (eicosanoids) with C20, including a cyclopentane ring.

52
Q

Prostaglandins are synthesized from what two things?

A

Arachidonic acid and other polyunsaturated fatty acids

53
Q

A subscript means what on a prostaglandin?

A

It means the number of carbon double bonds.

54
Q

Describe prostaglandin’s influence on the body.

A
  • Important in chemical cell communication (paracrine)
  • Functions like a hormone but not a hormone
  • Not stored but made as needed b/c of short half life.
55
Q

What are the three phases of lipid metabolism?

A

*Digestive phase (intra luminal phase)
*Absorptive phase (cellular phase)
* Transport phase

56
Q

What must happen before fats interact with pancreatic enzymes?

A

They must be emulsified by bile salts

57
Q

What are the two enzymes that processes fat?

A

Lipase and cholesterol esterase

58
Q

Lipase converts triglycerides into what?

A

diglycerides and monoglycerides.

59
Q

Cholesterol esters will be converted by lipase and cholesterol esterase into what?

A

Free cholesterol & free fatty acids

60
Q

What enzyme converts phospholipids into derivatives (lyso-derivatives)?

A

Phospholipase

61
Q

After enzyme action on triglycerides, what is formed?

A

mixed micelles (emulsified lipids)

62
Q

Micelles are made of what?

A

Monoglyceride, Diglyceride, Free fatty acid, free cholesterol, phospholipids, and bile acids

63
Q

Describe how micelles get absorbed into the intestines (absorptive phase).

A
  1. Micelles come in contact with mucosal cell
  2. Monoglyceride and fatty acids enter the ER of cell (via diffusion)
  3. Smaller Free fatty acids (10 or lower carbons) go directly into portal circulation & attach to albumin.
  4. Within intestinal cells the free fatty acids (10C +) are re-esterified to form Triglyceride and cholesterol esters.
  5. Lipids packaged into chylomicrons for transport (circulation)
64
Q

Describe the transport phase for the chylomicrons.

A
  1. Mucosal cells release chylomicron into abdominal lymphatics (several hrs after meal). This is considered reverse pinocytosis
  2. Chylomicrons enter the systemic circulation
  3. Chylomicrons are carried to the liver (via the bloodstream) and other tissue for use / metabolism.
65
Q

What is the apolipoprotein specific for chylomicron transport?

66
Q

What is the percentage make up of a chylomicron?

A
  • 82% triglyceride
  • 9% cholesterol
  • 7% phospholipids
67
Q

What is the destination for chylomicrons?

A

All tissue; adipose tissue is the principle site of uptake

68
Q

A chylomicron has offloaded triglycerides with the help of triglyceride lipase. What is the new protein carrier called?

69
Q

What is the fate of TG remnant remains?

A

Removed by the liver

70
Q

What is TG remnant remains made of?

A

Triglyceride poor, cholesterol rich, highly antherogenic lipoprotein

71
Q

What are the uses of lipid?

A
  1. Metabolic fuel
  2. Synthesis into other material
  3. Complexed into specific lipoprotein carriers by liver for transport
  4. Excess TG stored in adipose tissue
  5. Excess cholesterol excreted as bile salt
72
Q

Lipid synthesis is what kind of feedback?

A

Negative feedback

73
Q

What are the site of lipid synthesis?

A

Liver, intestines, and other tissue

74
Q

What tissue / organ is the primary site of endogenous lipid production?

75
Q

What are newly packed chylomicron called?

76
Q

Describe fatty acid synthesis

A

Successive addition of two carbon units derived from malonyl CoA which allow four carbon intermediates.

77
Q

What is the rate limiting step in fatty acid synthesis?

A

Acetyl CoA carboxylase + Biotin

78
Q

What inhibits acetyl CoA carboxylase?

A

Long chain acyl CoA.

79
Q

What activates Acetyl CoA Carboxylase?

80
Q

Fatty acid synthesis not only provides fatty acid but also ____

A

NADPH for other chemical pathways

81
Q

How many molecules of what is required to make one molecule of palmitate?

A

8 Acetyl CoA; Yields 8 NADPH via malic enzyme rxn

82
Q

14 molecules of NADPH is required to make one molecule of palmitate. Where do the 7 molecules of NADPH if fatty acid synthesis makes 8 NADPH?

A

The additional NADPH come from Pentose Phosphate Pathway

83
Q

List short term regulation of Acetyl CoA carboxylase (FA synthesis)

A

Allosteric activation - Citrate,
Allosteric inhibition - Long chain acyl CoAs,
Enhancement: Insulin, Dephosphorylation,
Inhibition: Glucagon, phosphorylation of cAMP

84
Q

List long term regulation of acetyl CoA carboxylase (FA synthesis)

A

Enhance enzyme synthesis: High carb diet, Fat free diet,
Decrease Enzyme synthesis: High fat diet, Fasting, Glucagon

85
Q

List long term regulation of fatty acyl CoA synthase

A

Enhanced Enzyme synth: High carb or Fat free diet
decreased Enzyme synth: High fat diet, fasting, glucagon

86
Q

What is the most commonly occuring fatty acid that is natural?

A

Palmitic Acid

87
Q

What is the purpose of the carnitine cycle?

A

To transport long fatty acid chains

88
Q

Describe beta oxidation

A

Removal of 2 carbons at the beta carbon (2nd carbon). The product is ATP and acetyl CoA

89
Q

Between alpha or beta oxidation, which yields more energy?

A

Beta oxidation. Alpha oxidation does not yield a lot (2 ATP less / double bond) however NADP + is made.

90
Q

The lack of alpha oxidation in a person leads to what? Describe the genetics aspect of it too.

A

Deficiency of alpha oxidation leads to Refsum’s disease. Its an autosomal recessive neurological disease.

91
Q

What is the fate of uneven carbon fatty acids?

A

They get oxidized to propionyl CoA and bicarbonate. They are then converted into succinyl CoA (a precursor of oxaloacetate).

92
Q

List apolipoprotein functions

A
  1. Maintain structural integrity of complex and ensure solubility of complex
  2. Activate important enzymes in lipoprotein metabolic pathways
  3. Facilitate uptake of lipoprotein into cells through their recognition by specific cell surface receptor.
    Note: Different Apo proteins require their own specific receptors
93
Q

Describe APO A - 1

A
  1. Major APO of HDL
  2. Structure protein activates LCAT
  3. Ligand for HDL binding
94
Q

Describe APO A-II

A
  1. Structural protein in HDL
  2. Activates LCAT
  3. Enhances hepatic TG lipase activity
95
Q

Describe APO B

A
  1. Large major structural protein in VLDL & LDL forms
  2. APO B 100 synthesized in liver found on VLDL, IDL, and LDL
  3. APO B-48 in intestine - Found on chylomicrons
96
Q

Describe APO E

A
  1. Binds to LDL receptor & chylomicron remnant receptor
  2. Several isoforms
97
Q

Describe APO (a)

A
  1. Strucural protein for Lp(a)
  2. Highly glycosylated apo
  3. May inhibit plasminogen binding
98
Q

What method would be use to separate lipoproteins?

A

*Ultracentrifugation based on density; VLDL, LDL, HDL, etc.
*Electrophoresis results in separation based on electrical charge of the
protein

99
Q

What would be needed for electrophoresis for lipoprotein separation?

A

1.Agarose or cellulose acetate
2. Barbital buffer or stain with fat stain
Bands that may appear are beta band (cholesterol and LDL), pre - beta band (TG and VLDL) , and alpha band (HDL)

100
Q

How would the layers look like after lipoprotein has been ultracentrifuged?

A
  • Chylomicrons
  • VLDL-Very Low Density Lipoproteins
  • IDL-Intermediate Density Lipoproteins
  • LDL-Low Density Lipoproteins
  • HDL-High Density Lipoproteins
101
Q

What are the units used to represent densities of lipoprotein?

A

Svedberg units (Sf); Low density = high Sf ; High density = low Sf units

102
Q

Describe how lipids are transported if they go through the endogenous pathway.

A

Hepatic lipids transported by VLDL and LDL to peripheral tissue.

103
Q

Describe how lipids are transported if they go through the reverse cholesterol pathway.

A

Transports cholesterol via HDL from peripheral tissues back to the liver for excretion or reuse.

104
Q

List the steps of reverse cholesterol pathway

A
  1. HDL produced mostly in liver
  2. In intestine, HDL binds free cholesterol from peripheral cells (macrophages)
    3.Cholesterol esterified by LCAT
  3. Cholesterol ester delivered to liver for eventual excretion
    **Direct uptake of HDL by liver via Apo A
    **    Apo E containing HDL binds LDL receptor or remnant receptor
    *** HDL exchanges cholesteryl ester to VLDL / LDL for TG
105
Q

What is the protein that facilitates transfers of cholesterol ester?

A

CETP, cholesteryl ester transfer protein slide 53

106
Q

Where does the HDL assembly take place?

A

In the blood circulation

107
Q

Describe LDL rececptors

A

▪ APO B-100 and APO E
▪ Cell binding
▪ Uptake and degradation of LDL
▪ Synthesis inhibited by high cholesterol level
▪ Defective receptors stimulates intracellular cholesterol synthesis

108
Q

Describe remnant receptors

A

▪ APO E
▪ Clearance of chylomicron and β-VLDL remnants from blood circulation

109
Q

Describe scavenger receptors

A

▪ Surface of macrophage and muscle cells
▪ Mediate removal of modified LDL from blood circulation
▪ Macrophage with high cholesterol accumulation: Foam cells

110
Q

How does cardiovascular disease happen?

A

From lipids being deposited into vessels over time. This leads to an occlusion.

111
Q

A high fat diet will lead to what?

A

Increase in endogenous production which may result in arterial plaque formation

112
Q

A disease or condition where plaque forms in the heart.

A

Coronary heart disease or coronary artery disease

113
Q

A disease where plaque forms in the arms and or legs is what?

A

Peripheral vascular disease

114
Q

A disease where plaque forms in the brain is what?

A

Cerebrovascular disease

115
Q

What kind of information is gained from a lipid profile?

A
  1. Total and HDL cholesterol
  2. Measured or calculated LDL cholesterol
  3. Triglyceride determination
  4. Lipoprotein electrophoresis
116
Q

List the formula for VLDL

117
Q

What is the formula for LDL?

A

LDL = total cholesterol - VLDL - HDL

118
Q

_______ relationship between HDL cholesterol & coronary risk

A

Inverse relationship

119
Q

What would invalidate LDL / HDL cholesterol risk ratio?

A

Chylomicron present ( sign of patient did not fast) and serum triglyceride greater than 400 mg/dL

Clinical Chemistry 2 (3 decks)

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