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PHRM 836 > Park - Exam 3 > Flashcards

Park - Exam 3 Flashcards

1
Q

Describe the use of glycerol and fatty acids in triacylglycerol in humans:

A

The liver and adipose tissues convert glucose to fatty acids and then to triacylglycerol.

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2
Q

True statements regarding fatty acids:

A
  • Saturated fatty acids have higher melting temperature than unsaturated fatty acids
  • w-3 and w-6 fatty acids are nutritionally essential fatty acids
  • polyunsaturated fatty acids such s arachidonic acid are used as precursors to make eicosanoids
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3
Q

How are fatty acids transported into mitochondria?

A
  • Fatty acids are activated by forming acyl CoA
  • Acyl CoA in the cytosol needs to be converted to acylcarnitine for transport into the mitochondria (rate-limiting step for fatty acid oxidation)
  • This is mediated by carnitine palmitoyltransferase I (CPT I)
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4
Q

What are the different end products of B-oxidation?

A
  • NADH, FADH, and Acetyl CoA
  • fatty acids with an odd number of carbons produce a propionyl CoA at the end of the cycle
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5
Q

Why is the transfer of acetyl coA needed for fatty acid synthesis?

A
  • Fatty acid synthesis occurs in the cytosol but acetyl CoA is produced in the mitochondria
  • Acetyl CoA is converted to citrate to be transported to the cytosol
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6
Q

What is the commitment step for fatty acid synthesis?

A

The conversion of acetyl CoA to malonyl CoA is the commitment step of fatty acid synthesis.

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7
Q

What is the role of malonyl CoA in fatty acid synthesis?

A
  • used as a substrate for fatty acid synthesis
  • inhibits fatty acid oxidation
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8
Q

What is the necessary reducing equivalent for fatty acid synthesis?

A

NADPH

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9
Q

What is the energy requirement for fatty acid synthesis?

A

Two NADPH are used per cycle

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10
Q

Explain the mechanism of desaturation of fatty acids in humans

A
  • double bonds can only be added up to the 9th carbon
  • these double bonds are added by desaturases
  • desaturases for 4,5,6 positions act only on fatty acids with a double bond at 9th carbon
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11
Q

What is the rate-limiting step for fatty acid oxidation?

A

conversion of Acyl CoA to acylcarnitine for transport into mitochondria

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12
Q

What is carnitine palmitoyl transferase I (CPT I) inhibited by?

A

malonyl CoA

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13
Q

How is cholesterol used in the human body?

A
  • precursor of bile acids and many steroid hormones
  • component of cell membranes (fluidity)
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14
Q

What is the commitment step for cholesterol synthesis?

A
  • HMG-CoA reductase converting HMG-CoA to mevalonate
  • irreversible rate-limiting step
  • uses NADPH as a reducing cofactor
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15
Q

Describe the solubility of cholesterol, cholesterol ester, and bile acids

A
  • solubility of cholesterol is very low in water
  • 0.2 mg / 100 mL
  • plasma concentration of cholesterol is much higher than that
  • the lipoproteins primarily transport cholesterol esters because they’re more hydrophobic
  • solubility of bile acids is higher
  • 390 mg / 100 mL
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16
Q

What are the guidelines for sorting lipoproteins?

A

density

  • high-density lipoprotein (HDL
  • low-density
  • intermediate-density
  • very-low-density
  • chylomicrons
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17
Q

What are the components of the core of lipoproteins?

A
  • the core is insoluble
  • triacylglycerol
  • cholesterol ester
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18
Q

What are the components of the shell of lipoproteins?

A
  • shell is amphipathic
  • phospholipids
  • cholesterol
  • apolipoproteins
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19
Q

True statements regarding fatty acid synthesis:

A
  • During fatty acid oxidation, two carbons are released at a time as acetyl CoA
  • During fatty acid synthesis, the growing fatty acids are carried by acyl carrier protein (ACP)
  • Acyl CoA suppresses the fatty acid synthesis
  • Conversion of acetyl CoA to malonyl CoA is the commitment step of fatty acid synthesis
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20
Q

The hydrolysis of one triacylglycerol generates one glycerol and three fatty acids. How many glucose molecules can be synthesized through gluconeogenesis from two molecules of triacylglycerol?

A

1

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21
Q

Regulation of fatty acid synthesis:

A
  • citrate activates fatty acid synthesis
  • isocitrate activates fatty acid synthesis
  • acyl coAs inhibit fatty acid synthesis
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22
Q

What is the role of LDL in lipid transport?

A
  • delivers cholesterol to peripheral tissues that require cholesterol for membrane formation or steroid hormone synthesis
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23
Q

What is the role of HDL in lipid transport?

A
  • HDL (rich in cholesterol but poor in triacylglycerol) carries cholesterol from the periphery to the liver –> excreted in bile as cholesterol
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24
Q

What is the role of VLDL and chylomicrons in lipid transport?

A
  • they transport triacyclglycerols to be used for energy or stored
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25
Q

List the pathological mechanisms for familial hypercholesterolemia:

A
  • inherited genetic condition –> elevated LDL at birth
  • mutation in either LDL receptor or apoB100 –> little or no LDL receptor production. Receptors can bind LDL, but cannot be internalized by endocytosis
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26
Q

Isoleucine, threonine, phenylalanine, tyrosine, and tryptophan are…

A

both glucogenic and ketogenic

  • note that these are all larger amino acids
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27
Q

Which amino acids are purely ketogenic?

A

lysine and leucine

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28
Q

Alanine (C3)

A

Pyruvate

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29
Q

Aspartate (4)

A

Oxaloacetate

30
Q

Glutamate (C5)

A

a-ketoglutarate

31
Q

What is the most abundant circulating amino acid?

A

glutamine

32
Q

How is ammonia transported to the liver?

A
  • glutamine and alanine
33
Q

Amino acid precursor to GABA

A

glutamate

34
Q

amino acid precursor to dopamine, norepinephrine, epinephrine

A

tyrosine

35
Q

amino acid precursor to serotonin, melatonin

A

tryptophan

36
Q

amino acid precursor to histamine

A

histidine

37
Q

amino acid precursor to oxalate

A

glycine

38
Q

Arrange the intermediates for epinephrine synthesis starting with tyrosine:

A

Tyrosine –> L-DOPA –> Dopamine –> Norepinephrine –> epinephrine

39
Q

How are kidney stones produced?

A
  • excessive production of oxalate forms the insoluble calcium oxalate salt, which may lead to kidney stones
  • lack of the enzyme activity converting glyoxylate to glycine causes primary hyperoxaluria
40
Q

What are the fates of cholesterol?

A
  • used as membrane component
  • stored in the liver as cholesterol ester
  • converted to bile acids
  • used as precursor for steroid synthesis
41
Q

Which amino acid can be made from pyruvate via transamination reaction?

A

alanine

42
Q

Which lipoprotein has the role in reverse cholesterol transport?

A

HDL

43
Q

What is least soluble in water?

A

cholesterol esters

44
Q

Rank the solubility of cholesterol, cholesterol esters, and cholic acid from highest to lowest:

A

cholic acid > cholesterol > cholesterol ester

45
Q

True descriptions of lipoproteins:

A
  • The uptake of LDLs by the liver is critical for the proper negative feedback on the cholesterol synthesis
  • IDLs have the lower density than LDLs
  • VLDLs are produced in the liver
  • Chylomicrons are produced in the intestines
46
Q

True descriptions regarding metabolism of amino acids:

A
  • excess amino acids in a diet are utilized as an energy source
  • ketogenic amino acids cannot be used at the carbon source for gluconeogenesis
  • nitrogen in amino acids is secreted as urea in humans
  • glutamine is the most abundant circulating amino acid in humans
47
Q

What is a nucleoside?

A

ribose + nucleobase

48
Q

What is a nucleotide?

A

nucleoside + phosphate

49
Q

Nucleobase: adenine

A

adenosine

50
Q

nucleobase: guanine

A

guanosine

51
Q

nucleobase: cytosine

A

cytidine

52
Q

nucleobase: uracil

A

uridine

53
Q

nucleobase: hypoxanthine

A

inosine

54
Q

nucleobase: xanthine

A

xanthosine

55
Q

nucleobase: orotate

A

orotidine

56
Q

What is the commitment step for the de novo synthesis of purine bases?

A

PRPP –> 5-phosphoribosylamine

  • mediated by PRPP-amidotransferase
57
Q

List the allosteric regulators for purine synthesis:

A
  • IMP, GMP, AMP – negative
  • PRPP – positive
58
Q

What is the end product of degradation of purine nucleobases?

A

uric acid

59
Q

Explain the mechanism of allopurinol in gout prevention:

A
  • structural isomer of hypoxanthine
  • xanthine oxidase inhibitor
  • reduces the production of uric acid
  • increases the utilization of hypoxanthine through the salvage pathway, which reduces de novo purine synthesis
60
Q

List the necessary biochemical reaction for the synthesis of deoxyribose nucleotides for DNA synthesis:

A
  • ribonucleotide reductase converts NDP to dNDP – which is the rate-limiting step for dNTP
61
Q

Explain the antiviral mechanism for acyclovir:

A
  • converted to the monophosphate by a HSV-thymidine kinase
  • the triphosphate is used as a substrate for the HSV DNA polymerase, causing chain termination
62
Q

Explain the antiviral mechanism of sofosbuvir:

A
  • prodrug – rapidly converted to the active agent in vivo
  • activation of the corresponding nucleoside is much slower
  • the active agent is a potent inhibitor of NS5B, which is a RNA-dependent RNA polymerase
63
Q

Describe the role of fructose 2,6-bisphosphate in regulation of glycolysis and gluconeogenesis:

A
  • it increases glycolysis and suppresses gluconeogenesis
64
Q

What is the catalytic activity of 6-phosphofructo-2-kinase/fructose 2,6 bisphosphatase in the liver after glucagon or epinephrine has been released?

A
  • the enzyme switches to a phosphatase –> decreasing the fructose 2,6-P level
65
Q

What is the catalytic activity of 6-phosphofructo-2-kinase/fructose 2,6 bisphosphatase in the heart after epinephrine has been released?

A
  • enzyme switches to a kinase –> increases fructose 2,6-bisphosphate
66
Q

Explain the action of protein kinase A on the activity of pyruvate kinase and the consequence in glycolysis?

A
  • Protein kinase A inactivates pyruvate kinase
  • PEP is not converted to pyruvate
  • glycolysis is suppressed
67
Q

Identify genes induced and suppressed by the action of glucagon:

A
  • repressed: glucokinase, 6-phosphofructo-1-kinase, pyruvate kinase
  • induced: PEP carboxykinase, fructose 1,6-bisphosphatease, glucose 6-phosphate (responsive to cAMP)
68
Q

What impact does glucagon have on glycogen metabolism?

A
  • glucagon stimulates glycogen breakdown in liver
69
Q

Contrast insulin and glucagon:

A

Insulin reduced blood glucose levels by promoting glycogen synthesis whereas glucagon raises blood glucose levels by promoting glycogen breakdown

Insulin lowers cAMP whereas glucagon increases it

70
Q

Contrast the effects of glucagon and insulin on lipid metabolism:

A
  • glucagon promotes fatty acid oxidation
  • insulin promotes fatty acid synthesis
71
Q

Describe the Warburg effect in cancer cells:

A
  • even when O2 is plentiful, cancer cells convert glucose to lactate
  • cancer cells use glucose 200x more than normal cells

PHRM 836 (3 decks)

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