Exam 5 study guide Flashcards
1
Q
where does desaturation of FAs occur?
A
in the ER
2
Q
three glycerolipids (know structures)
A
TAG, glycerophospholipid, ether glycerolipid
3
Q
three phospholipids (know structures)
A
glycerophospholipids, ether glycerolipids, sphingophospholipids
4
Q
major cholesterol intermediates
A
acetyl CoA to mevalonate to squalene to lanosterol to cholesterol
5
Q
point of action of statin drugs
A
HMG CoA reductase
6
Q
three eicosanoids
A
leukotrienes, prostaglandins, thromboxanes
7
Q
eicosanoid function
A
local hormones of inflammatory response
8
Q
most common precursor of eicosanoids
A
arachidonic acid
9
Q
where do NSAIDs act?
A
inactivate COX
10
Q
four enzymes from pamitoyl to ceramide
A
serine palmitoyltransferase, 3-ketoshpinganine reductase, dihydroceramide synthase, dihydroceramide desaturase
11
Q
fates of ceramide
A
shingomyelin, glucosylceramide, shingosine (then S1P)
12
Q
SMS
A
sphingomyelin synthase. ceramide to sphingomyelin
13
Q
GCS
A
glucosylceramide synthase. ceramide to glucosylceramide
14
Q
ceramidase
A
ceramide to sphingosine
15
Q
SK
A
sphingosine kinase. sphingosine to S1P
16
Q
therapeutic targets in SL metabolism
A
enhance SPT (synth of sphinganine, ceramide precursor)), enhance ceramide synthase. inhibit GCS (glucosylceramide synthase)
17
Q
bile salts
A
emulsify fat. form micelles. made in liver. secreted by gallbladder
18
Q
adipose lipases
A
ATGL and HSL. specific for triglyceride. under hormonal regulation. subsequent enzymes are di and mono glyceride specific. rate limiting.
19
Q
pancreatic lipases (intestinal lipases)
A
made in pancreas. lipases cleave fatty acids from C1 and C3 position of TAG. phospholipase A2 and esterases also made and released by pancreas
20
Q
colipase
A
assists lipase binding to fat
21
Q
activates the carboxyl group of the fatty acid
A
Acyl CoA synthetase
22
Q
transport of fatty acids into mitochondria
A
acyl CoA synthetase (activates FA and brings into intermembrane space). CPT1 makes fatty acyl carnitine. translocase moves fatty acyl carnitine into matric. CPT-II makes fatty acyl coa
23
Q
beta oxidation key steps
A
sepcific dehydrogenase between alpha dn beta carbons. hydratase places alcohol on beta carbon. dehydrogenase places ketone on beta carbon. thiolase releases acetyl CoA
24
Q
blocks conversion of fatty acyl coa to fatty acyl carnitine (CPT1)
A
malonyl coa
25
acetyl coa carboxylase rxn
acetyl coa to malonyl coa
26
activates acetyl coa carboxylase
insulin
27
inhibits beta oxidation
high atp inhibits ETC. inhibits NADH and FADH2. inhibits beta oxidation
28
three ketone bodies
acetone, acetoacetate, alpha hydroxybutyrate
29
lipoproteins increasing in density
chylomicrons, VLDL, IDL, LDL, HDL
30
LDL receptor
recognizes apoB100 and apoE. binds LDL and VLDL, IDL, and chylomicron remnants.
31
ldl receptor mechanism
receptor mediated endocytosis, fuses with lysosome, releases AA and FA
32
artherosclerosis
high low density lipoprotein. driven by oxidized LDL
33
bind oxidized LDL and lead to formation of foam cells
scavenger receptors
34
three phases of conversion of dietary proteins to amino acids
gastric, pancreatic, inetestinal
35
gastric phase
low ph denatures and pepsin is protease. pepsin secreted by chief cells as zymogen
36
Where are trypsin, chymotrypsin and elastase produced?
pancreas
37
where is pepsin produced?
as zymogen, pepsinogen, in stomach chief cells
38
Which amino acid residues are involved in the peptide bond that is cleaved by pepsin
Phe, Tyr, Glu, Asp
39
Which amino acid residues are involved in the peptide bond that is cleaved by trypsin
Arg, Lys
40
Which amino acid residues are involved in the peptide bond that is cleaved by chymotrypsin
Phe, Tyr, Trp. Leu
41
Which amino acid residues are involved in the peptide bond that is cleaved by elastase
ala, gly, ser
42
activation of pepsin
gastrin stimulates chief cells to release pesinogen. pepsinogen autoactivates or by HCl
43
activation of trypsin
trypsinogen released in pancreas. activated by enteropeptidase and by autocatalysis
44
activation of chymotrypsin and elastase
released in pancreas as chymotrypsinogen and proelastase. Activated by Trypsin
45
What is the role of enteropeptidase?
cleaves trypsinogen to form trypsin
46
how are AA transported to the blood?
via intestinal epithelial cells. Use Na and H dependent transporters to bring in AA. ATP active transporters to maintain Na gradient. Facilitated transporter releases into blood.
47
enzymes in intestine
peptidases (endo, di, and amino peptidases)
48
AA transporters
neutral, basic, acidic, imino, dipeptide, tripeptide transporters
49
how is nitrogen obtained for AAs
from dietary proteins or breakdown of body proteins
50
how is nitrogen incorporated into AAs
ammonia produced by inetestinal tract or AA catabolism. incorporated into glutamate and glutamine
51
aminotransferases (transaminase) function and coenzyme
remove alpha amino group from AA and transfer to alpha keto acid. PLP is coenzye that carries amino group
52
____ and ___ play key role in carrying nitrogen from peripheral tissues to the liver
glutamine and alanine
53
what is the role of glutamine in the fasting state?
muscle releases glutamine which goes to kidney for excretion as urine
54
alanine aminotransferase during AA degradation in liver
alanine + alpha ketoglutarate goes to pyruvate + glutamate
55
aspartate aminotransferase during AA degradation in liver
OAA + glutamate goes to aspartate +alpha ketoglutarate
56
PLP reactions
contains aldehyde group that forms a schiff base. cofactor of aminotransferases. in absence of substrate, aldehyde is attached to lysine of enzyme
57
PLP reactions
contains aldehyde group that forms a schiff base. cofactor of aminotransferases. in absence of substrate, aldehyde is attached to lysine of enzyme
58
consequence of low vit B6
can't make PLP
59
vitamin required for PLP synth
B6
60
how is ammonia produced from glutamate?
glutamate dehydrogenase. makes NH4+ NADH and alpha ketoglutarate
61
how is ammonia produced from glutamine?
glutaminase. makes NH4+ and glutamate
62
what are the biological properties of Urea
47% nitrogen, uncharged, water soluble, nontoxic
63
sources of ammonia in urea cycle
nitrogen of most AA transferred to alpha ketoglutartate then to glutamate. glutamte nitrogen converted to ammonia then to urea
64
enzymes of urea cycle starting with NH4
CPS-1, ornithine transcarbamoylase, argininosuccinate synthetase, argininosuccinate lyase, arginase
65
intermediate that links urea cycle to TCA cycle. How?
fumarate converted to malate for entry into TCA
66
intermediate that links urea cycle aminotransferases. How?
fumarate. converted to malate then to OAA. OAA + glutamate goes to alpha ketoglutarate and aspartate
67
primary substrate regulation of urea cycle
ammonia production leads to higher rate of Urea production
68
carbamoyl phosphate synthetase 1 promoted by ?
NAG
69
NAG function
promotes carbamoyl phosphate synthesis for Urea cycle
70
NAG synthesis
NAG synthetase makes NAG from glutamate and acetyl Coa
71
NAG synthetase reaction
glutamate + acetyl Coa goes to NAG
72
Diet induced urea cycle regulation
starvation or high protein represses urea cycle enzymes
73
role of glutamate in urea production?
used to make NAG for CPS-1 stimulation. makes ammonia via GDH
74
how does alanine produce glucose and urea in the fasting state
alanine aminotransferase generates pyruvate and glutamate. pyruvate can make glucose and glutmate can make urea
75
hyperammonemia
hereditary deficiency in any urea cycle enzyme leads to elevated ammonia in blood
76
treat urea cycle defects
limit protein (less N), add alpha keto analogs of essential AA to diet. consume arginine and citrulline to increase urea production. levulose acidifies colon. antibiotics to kill ammonia producing bacteria. sodium benzoate binds glycine and is excreted in feces
77
which urea cycle defects produce ammonia at high levels
CPS-1 defect is worst. ornithine transcarbamoylase and argininosuccinate synthetase 2nd worst.
78
why is an argininosuccinate lyase defect not as debilitating
argininosuccinate can be excreted in feces
79
postulate biochemical mechanism for neurotoxic effects of hyperammonemia
high brain ammonia. high glutamine synthetase (depletes glutamate). high glutamate dehydrogenase to form glutamate (depletes alpha ketoglutarate and OAA, slows TCA)
80
essential AA
PVT TIM HALL (FVT TIM HLL). phenylalanine (not proline), arginine is adult nonessential
81
two nonessential AA made from essential
cysteine made from methionine. Tyrosine made from phenylalanine.
82
effect of folate deficiency
can't make FH4 (one carbon carrier). Results in hemoglobin poor RBCs. transfers methyl to B12
83
effect of folate deficiency on glycine metabolism
THF is required for conversion between serine
84
gluocogenic and ketogenic AAs
PITTT
85
purely ketogenic AAs
LL (lysine and leucine)
86
glycolytic and TCA intemediates that give rise to nonessential AAs
3-phosphoglycerate, pyruvate, OAA, alphaketoglutarate
87
3-phosphoglycerate gives rise to these AAs
glycine, serine, cysteine
88
pyruvate gives rise to this AA
alanine
89
OAA gives rise to these AAs
Aspartate, asparagine
90
alpha-ketoglutarate gives rise to these AAs
glutamate, glutamine, proline, arginine
91
three dominant alpha ketoacid - alpha amino acid pairs
a-ketoglutarate/glutamate,
92
AAs that converge on pyruvate
WTC GAS
93
AAs that converge on a-ketoglutarate
RH QEP
94
AAs that converge on fumarate
FYD
95
AAs that converge on Succinyl CoA via Propionyl
IMTV
96
two rxns that involve B12
methylmalonyl CoA to succinyl coA. homocysteine to methionine
97
primary role of SAM
transfers methyl groups to creatine, phosphatidylcholine, epinephrine, melatonin
98
how is SAM made
from methionine and ATP
99
connect FH4, b12 and SAM
FH4 passes methyl to B12, B12 makes methionine. methionine makes SAM
100
BH4 made from?. regenerated from ?
GTP . BH2
101
reaction catalyzed by BH4 (tetrahydrobioterin)
phenylalanine to tyrosine
102
regenerates BH4 from BH2
dihydropteridine reductase
103
dihydropteridine reductase
BH2 to BH4
104
glucose alanine cycle
converts gluocse to alanine in muscle. alanine to glucose in liver. pyruvate intermediate. ala-pyruvate conversion requires Ala aminotransferase
105
shared degradation pathway of valine, isoleucine, and leucine (BCAAs)
plp-dependent branched chain aminotransferase (makes NADH), followed by branched chain alpha keto acid dehdrogenase (makes FADH2 and/or NADH)
106
disrupted BCAA catabolism
maple syrup urine when missing branched chain alpha keto acid dehydrogenase. excrete keto acids. mental retardation, short lifespan
107
sources of carbons and nitrogens in purine ring
glycine backbone, nitrogens from glutamine
108
source of ribose in purine synth
ribose-5-phosphate
109
role of folic acid in purine synth
introduce formyl groups
110
branch point in purine synthesis
IMP goes to either XMP (to GMP) or adenylosuccinate (to AMP)
111
IMP to XMP enzyme
IMP dehydrogenase
112
IMP to adenylosuccinate
anenylosuccinate synthetase
113
major regulated enzyme in purine synth
PRPP synthetase
114
PRPP synthetase regulation
inhibited by GDP and ADP
115
IMP branch point regulation
feedback inhibited by GMP or AMP
116
how are purines degraded
converted to xanthine then to uric acid for urine excretion. Uses xanthine oxidase
117
converts AMP to IMP
adonosine deaminase
118
defective adenosine deaminase
SCIDS
119
formation of carbamoyl phosphate in pyrimidine synth
uses CPS2. In cytosol. Uses Gln and CO2
120
primary regulated enzyme of pyrimidine synthesis
CPS2. inhinited by UTP. activated by PRPP
121
primary regulated enzyme of pyrimidine synthesis
CPS2. inhinited by UTP. activated by PRPP
122
pyruvate carboxylase reaction
Pyruvate + ATP makes OAA
123
malic enzyme reaction
malate makes pyruvate and NADPH
124
acetyl coa carboxylase reaction
acetyl coa + CO2 + biotin + ATP makes malonyl CoA
125
acetyl coa carboxylase activted by ?
citrate and phosphatase (via insulin)
126
acetyl coa carboxylase inhibited by ?
palmitoyl CoA
127
catabolism
the breakdown of complex molecules in living organisms to form simpler ones, together with the release of energy; destructive metabolism.
128
citrate produces two key intermediates in cytosol
pyruvate (via OAA, reconverted to citrate), acetyl CoA and NADPH (for FA synthase)
129
citrate lyase reaction and regulation
citrate + CoASH + ATP goes to OAA and acetyl CoA. induced by insulin
130
rate limiting enzyme of FA synthesis
acetyl CoA carboxylase
131
net reaction of fatty acid synthase complex
1 acetyl CoA + 7 malonyl CoA + 14 NADPH goes to 1 palmitate + 7 CO2 + 14 NADP+ + 8 CoA + 6 H20
132
FAS contains an ACP that contains this residue for carrying acyl groups
phosphopantetheine
133
movement of electrons for fatty acid desaturation
2 electrons from NADH to Cytochrome b5 reductase to cytochrome b5 to desaturase
134
arachidonic acid is synthesized from ?
linoleic
135
EPA and DHA synthesized from ?
linolenic
136
glucagon effect on TAG lipase
activates glucagon receptor, makes cAMP, activates PKA, activates TAG lipase
137
forms backbone of TAG
glycerol 3 phosphate (G3P. from DHAP)
138
arachidonic acid formula
20:4 n-6
139
arachidonic acid is released from membrane by
phospholipase A2 or C
140
generates ceramide from sphingomyelin
shingomyelinase
141
drug that enhances ceramide synthesis
4-HPR
142
drug that slows cermide glucosylation
tamoxifen
143
where are chylomicrons made
intestinal epithelial cells (mucosa)
144
chylomicron synthesis. precursors, intermediates, locations
FA and 2-MG enter intestinal epithelial cells. TG made by mechanism different than that in liver (no phosphatidic acid required). TG, cholesterol, phospholipids and apoB48 make nascent chylomicron. released into lymph
145
B48
major apoprotein of chloymicrons. similar to apoB100 found in VLDL. used in localization
146
lipoprotein lipase activation and function
activated by apoC-2. releases FA and glycerol from chlomicron. FA picked up by albumin for entry into tissue.
147
free fatty acid concentration. serum albumin bound concentration
0.1 nM free. 1 mM bound
148
lipolyis
brekak down of TAG in adipose to glycerol and FA
149
fate of glycerol in adipose
cannot be recycled. goes to blood and used as carbon source for gluconeogenesis.
150
three fates of Fatty Acyl Coa
Energy (beta oxidation or ketogenesis), lipids (sphingo, phospho), storage (TAG)
151
4 enzymes (general) of beta oxidation
specific dehydrogenase, hydratase, dehydrogenase, thiolase
152
inhibits acetyl CoA to malonyl CoA
AMP-PK
153
inhibits beta oxidation
high ATP inhbits ETC inhibits NADH production required for beta oxidation
154
beta oxidation of odd chains yields ?
propionyl CoA
155
coenzmyes required to convert propionyl CoA to succinyl coA
biotoin and B12
156
what is different about peroxisonal beta oxidation
for veryl ong fatty acids. requires FAD dependent acyl coA oxidase
157
branched chain FA degraded by?
alpha oxidation
158
where are ketone bodies used and what are they converted to
tissues other than liver. converted to acetyl CoA
159
where are HDL and VLDL assembled
ER of liver cells
160
Apo
protein in lipid free form
161
lipoprotein structure
neutral lipid core (cholesterol ester, TAG), polar surface monolayer (apoprotein, cholesterol, phospholipid)
162
major apolipoproteins on chlomicrons
apoB48, apoCII, apoE
163
apoCII function
activates lipoprotein lipase (releases TG*)
164
apoE function
drives chylomicron back to liver
165
path of VLDL after synth in liver to IDL
nascent VLDL contains apoB100. in blood, HDL donates apoCII and apoE to become mature VLDL. LPL breaks down into FA + glycerol + IDL. half of VLDL remanants goes to liver, other half is IDL.
166
path of IDL upon formation from VLDL to formation of LDL
TG further removed by HTGL (hepatic TG lipase) to form IDL remants. 60% taken up by liver via apoB100. 40% carrier to extrahepatic tissue
167
3 ways to synth HDL
in liver and intestine. budding from chylomicrons and VLDL as they are digested by LPL. from apoA1 (accumulates other components). Accumulation does not require enzymatic activity.
168
reverse cholesterol transport. enzyme
HDL can remove cholesterol from enriched cells and return to liver. modifies using LCAT to ensure HDL retains choleterol
169
transfers cholesterol esters from HDL to VLDL in exchange for TG
CETP exchange pathway
170
kwashiorkor
inadequate protein intake
171
gastric phase
acetylcholine and gastrin stimulated by food. decreased pH deantures. chief cells exrete pepsinogen. cleaved to pepsin. pepsin generates large peptides and some free AA
172
acute pancreatitis
zymogens activated inside pancreas cells
173
function of epithelial cells in absorbing AA
AA, di, and tripeptides brought into cells using Na-dependent transporters. neutral dipeptides use H-dependent transporter. AA leave epithelial cell via facillitated transport
174
defective neutral AA transporter
Hartnup disease
175
proteolytic pathways to remove damaged protein
ubiquitin dependent and lysosomal dependent
176
two common AA released from muscle into blood
glutamine (to kidney or gut) alanine (to liver)
177
fates of glutamine released from muscle into blood
to kidney (converted to alanine and ammonia (urine excretion)) or to gut (coverted to alanine and ammonium, both go to liver)
178
3 major a-amino / a-ketoacid pairs
alanine/pyruvate, aspartate/OAA, glutamate/aKG
179
PLP bond cleavage is under __ control
stereoelectronic
180
glutamine synthetase raction
glutamate + NH4 + ATP goes to glutamine
181
glutamate dehydrogenase reaction in liver
aKG + NH4 + NADPH goes to glutamate
182
entry of glutamate into urea cycle
GDH produces NH4 for entry. aspartate aminotransferase generates aspartate for entry
183
ATP requiring enzymes of urea cycle
CPS1 (2 ATP), argininosuccinate synthetase (1)
184
humans excrete # urea/year
10kg
185
AA that produces gulcose and urea during fasting state
alanine
186
Ornithine transcarbamoyltransferase deficiency
carbamoyl phosphate accumulates, orotic acid excreted
187
blocks reduction step of dihydrofolate reductase
methotrexate
188
dihydrofolate reductase reaction
folate + 2 NADPH goes to FH4
189
major 1-carbon pool source
serine
190
homocysteine to methionine requires this coenzyme
B12
191
does PLP produce ammonia?
NO. group transfers only
192
three reactions of biopterin
F to Y. Y to DOPA. W to 5-HTP
193
tyrosine aminotransferase deficiency
tyrosinemia
194
homogentisate oxidase deficiency
alkaptonuria
195
furmarylacetoacetate hydrolase deficiency
type 1 tyrosinemia
196
catecholamines made from tyrosine
DOPA, dopamine, norepinephrine, epinephrine
197
transfers methyl to epinephrine
SAM
198
purine synthesis rate determined by?
PRPP availability
199
committed step in purine synth
Gln:PRPP amidotransferase attaches Gln to PRPP
200
first two enzymes of purine synthesis pathway
PEPP synthetase, Gln:PRPP amidotransferase
201
blocks xanthine oxidase activity
allopurinol
