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.
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
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)
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
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
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.
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
8
Q
What is the necessary reducing equivalent for fatty acid synthesis?
A
NADPH
9
Q
What is the energy requirement for fatty acid synthesis?
A
Two NADPH are used per cycle
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
11
Q
What is the rate-limiting step for fatty acid oxidation?
A
conversion of Acyl CoA to acylcarnitine for transport into mitochondria
12
Q
What is carnitine palmitoyl transferase I (CPT I) inhibited by?
A
malonyl CoA
13
Q
How is cholesterol used in the human body?
A
- precursor of bile acids and many steroid hormones
- component of cell membranes (fluidity)
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
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
16
Q
What are the guidelines for sorting lipoproteins?
A
density
- high-density lipoprotein (HDL
- low-density
- intermediate-density
- very-low-density
- chylomicrons
17
Q
What are the components of the core of lipoproteins?
A
- the core is insoluble
- triacylglycerol
- cholesterol ester
18
Q
What are the components of the shell of lipoproteins?
A
- shell is amphipathic
- phospholipids
- cholesterol
- apolipoproteins
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
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
21
Q
Regulation of fatty acid synthesis:
A
- citrate activates fatty acid synthesis
- isocitrate activates fatty acid synthesis
- acyl coAs inhibit fatty acid synthesis
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
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
24
Q
What is the role of VLDL and chylomicrons in lipid transport?
A
- they transport triacyclglycerols to be used for energy or stored
25
List the pathological mechanisms for familial hypercholesterolemia:
- 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
26
Isoleucine, threonine, phenylalanine, tyrosine, and tryptophan are...
both glucogenic and ketogenic
- note that these are all larger amino acids
27
Which amino acids are purely ketogenic?
lysine and leucine
28
Alanine (C3)
Pyruvate
29
Aspartate (4)
Oxaloacetate
30
Glutamate (C5)
a-ketoglutarate
31
What is the most abundant circulating amino acid?
glutamine
32
How is ammonia transported to the liver?
- glutamine and alanine
33
Amino acid precursor to GABA
glutamate
34
amino acid precursor to dopamine, norepinephrine, epinephrine
tyrosine
35
amino acid precursor to serotonin, melatonin
tryptophan
36
amino acid precursor to histamine
histidine
37
amino acid precursor to oxalate
glycine
38
Arrange the intermediates for epinephrine synthesis starting with tyrosine:
Tyrosine --> L-DOPA --> Dopamine --> Norepinephrine --> epinephrine
39
How are kidney stones produced?
- 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
What are the fates of cholesterol?
- used as membrane component
- stored in the liver as cholesterol ester
- converted to bile acids
- used as precursor for steroid synthesis
41
Which amino acid can be made from pyruvate via transamination reaction?
alanine
42
Which lipoprotein has the role in reverse cholesterol transport?
HDL
43
What is least soluble in water?
cholesterol esters
44
Rank the solubility of cholesterol, cholesterol esters, and cholic acid from highest to lowest:
cholic acid > cholesterol > cholesterol ester
45
True descriptions of lipoproteins:
- 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
True descriptions regarding metabolism of amino acids:
- 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
What is a nucleoside?
ribose + nucleobase
48
What is a nucleotide?
nucleoside + phosphate
49
Nucleobase: adenine
adenosine
50
nucleobase: guanine
guanosine
51
nucleobase: cytosine
cytidine
52
nucleobase: uracil
uridine
53
nucleobase: hypoxanthine
inosine
54
nucleobase: xanthine
xanthosine
55
nucleobase: orotate
orotidine
56
What is the commitment step for the de novo synthesis of purine bases?
PRPP --> 5-phosphoribosylamine
- mediated by PRPP-amidotransferase
57
List the allosteric regulators for purine synthesis:
- IMP, GMP, AMP -- negative
- PRPP -- positive
58
What is the end product of degradation of purine nucleobases?
uric acid
59
Explain the mechanism of allopurinol in gout prevention:
- 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
List the necessary biochemical reaction for the synthesis of deoxyribose nucleotides for DNA synthesis:
- ribonucleotide reductase converts NDP to dNDP -- which is the rate-limiting step for dNTP
61
Explain the antiviral mechanism for acyclovir:
- 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
Explain the antiviral mechanism of sofosbuvir:
- 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
Describe the role of fructose 2,6-bisphosphate in regulation of glycolysis and gluconeogenesis:
- it increases glycolysis and suppresses gluconeogenesis
64
What is the catalytic activity of 6-phosphofructo-2-kinase/fructose 2,6 bisphosphatase in the liver after glucagon or epinephrine has been released?
- the enzyme switches to a phosphatase --> decreasing the fructose 2,6-P level
65
What is the catalytic activity of 6-phosphofructo-2-kinase/fructose 2,6 bisphosphatase in the heart after epinephrine has been released?
- enzyme switches to a kinase --> increases fructose 2,6-bisphosphate
66
Explain the action of protein kinase A on the activity of pyruvate kinase and the consequence in glycolysis?
- Protein kinase A inactivates pyruvate kinase
- PEP is not converted to pyruvate
- glycolysis is suppressed
67
Identify genes induced and suppressed by the action of glucagon:
- repressed: glucokinase, 6-phosphofructo-1-kinase, pyruvate kinase
- induced: PEP carboxykinase, fructose 1,6-bisphosphatease, glucose 6-phosphate (responsive to cAMP)
68
What impact does glucagon have on glycogen metabolism?
- glucagon stimulates glycogen breakdown in liver
69
Contrast insulin and glucagon:
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
Contrast the effects of glucagon and insulin on lipid metabolism:
- glucagon promotes fatty acid oxidation
- insulin promotes fatty acid synthesis
71
Describe the Warburg effect in cancer cells:
- even when O2 is plentiful, cancer cells convert glucose to lactate
- cancer cells use glucose 200x more than normal cells
PHRM 836
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