NST 160 MIDTERM EXAM QUESTIONS
WITH COMPLETE ANSWERS
___ is the predominant zeitgeber for the SCN clock while clocks in peripheral tissues
can be entrained by ___ - Answer-light; food
nutrient sensing by nuclear hormone receptors can alter circadian rhythms by
changing expression of clock genes
ex) Rev-erb (____ ) and Bmail (____) - Answer-PPAR gamma & alpha
PPAR alpha
peripheral clocks regulate metabolism in part through circadian expression of ___
and ____ - Answer-nuclear hormone receptors and key metabolic hormones
the majority (70%) of the body's 3-5g of iron is utilized by ____ cells - Answer-
erythroid
nonheme iron uptake - Answer-1. ferric --> ferrous
2. reductase duodenal cytochrome b
3. transport across the apical membrane via DMT1 (divalent metal transporter 1)
4. export of Fe2+ by basolateral transporter ferroportin
5. hephaestin converts back to Fe3+ on plasma membrane
6. circulating Fe3+ bound by plasma iron carrier transferrin; delivers iron to erythroid
bone marrow and other tissues
7. binds to transferrin receptor and undergoes endocytosis
8. iron release accomplished by acidification of endosome to pH~5.5
9. iron reduced by the STEAP family of ferrireductases and transported out of the
late endosome by DMT1 into the cytoplasm
10. when trasnferrin pool becomes saturated, non-transferrin bound iron can also
enter cells directly through DMT1)
11. some stored in ferritin as a buffer
12. Fe3+ to Fe2+ to be released into circulation
mechanisms to prevent iron overload - Answer-1. transferrin-bound iron can come
together with HFE and interact with TfR2 on hepatocytes, triggering signaling
cascade that leads to the secretion of Hepcidin
2. Hepcidin can be sensed by intestinal cells (and macrophages) and cause
internalizationa nd degradation of ferroportin, thus trapping dietary iron in the
intestine
-any mutations in these lead to iron overload disease
pro-inflammatory cytokine ___ causes, through activation of hepatic IL-6 receptors, a
large increase in hepcidin leading to suppression of absorption and reduced
circulating iron levels - Answer-IL6
symptoms of ACD (anemia of chronic disease) - Answer--feeling weak or tired
-headache
-paleness
,-shortness of breath
____ is a functional aconitase, interconverting citrate and isocitrate in the cytosol.
this contains a 4Fe-4S cluster in its active site - Answer-IRP1
the iron-sulfur cluster IRP1 is readily destabilized by _____. if the iron-sulfutre cluster
is not replaced, IRP1 assumes a IRE binding conformation - Answer-oxidants
what is important for IRP binding? - Answer-the GUGAC loop and unpaired C in the
stem of IRE
in iron starvation, what will be active? - Answer-IRP
risk of developing T2DM in men and women with elevated serum ferritin levels are
____ fold as high as in persons with normal iron levels approaching the risk
engendered by obesity. reason? - Answer-5 to 3.6
reason: unclear, but may be due to altered levels of adipokines
iron deficiency =
iron overload = - Answer-anemia
heart and liver failure (hereditary hemochromatosis and transfusional iron overload)
mutations in the hepcidin pathway lead to _______ - Answer-hereditary
hemochromatosis
T/F : inflammmation can cause decrease hepcidin secretion and in the case of
chronic inflammation can result in ACD - Answer-FALSE - increase hepcidin, so
leads to buildup of iron
T/F: mutations in IREs can prevent IRP binding and lead to aberrant protein
expression - Answer-True
T/F: pathological and dietary iron deficiency increases T2Dm susceptibility - Answer-
False; iron overload
an adult on a low-cholesterol diet typically synthesizes about __ mg of cholesterol
per day - Answer-800
which terminus of SREBP (transcription factor) binds to ___, which acts as a sterol
sensor - Answer-C-termus; SCAP
in sterol depleted cells, Scap escorts SREBP to the Golgi by binding to ___ (a
component of the ___ protein coat) - Answer-Sec 24, CopII
in the Golgi, SREBP is proteolytically processed by two proteases (___ and ___) to
generate the nuclear form that activates genes for cholesterol synthesis and uptake -
Answer-S1P and S2P
binding of cholesterol to SCAP's sterol-sensing domain causes conformational
change that prevents interactions with the ___ proteins - Answer-CopII
, Sterol mediated ER retention of Scap/SREBP is enhanced by binding to the ER
resident protein __ - Answer-Insig
___ is an SREBP target gene, thus SREBP induces the (mRNA) expression of its
own negative regulator - Answer-Insig1
when cells are deprived of sterols, Insig is rapidly ____ and ___ by proteasomes -
Answer-ubiquitinated and degraded
depletion of cholesterol leads to(6) - Answer-- dissociation of SREBP/Scap from
Insig
-Insig ubiquitination and degradation
-SREBP/Scap binding to CopII proteins and translocation to the Golgi
-SREBP processing and translocation to the nucleus
-activation of SREBP target genes increasing cholesterol biosynthesis and uptake
-increased Insig synthesis but rapid degradation keeps levels low unless sufficient
cholesterol accumulates to bind Scap
what is "convergent inhibition" - Answer-newly supplied cholesterol and newly
synthesized Insig when you block SREBP
altered autophagic degradation of glycogen stores may underlie the basis of different
muscle disorders such as ___, an X-linked vascular myopaty - Answer-Danon
disease
autophagy can indirectly contribute to glucose metabolismm by modulating ____ and
function as macroautophagy is required to prevent the accumulation of dysfunctional
mitochondria that can damage the cells through the generation of _____ - Answer-
pancreatic B-cell mass
reactive oxygen species
starvation activates macroautophagy in part through inhibition of ____ via decreased
___ and active ____ - Answer-mTORCI; AA and active AMPK
alterations in autophagy are associated with ___ and ____ - Answer-metabolic
disorders and aging
the yeast protein ____ was isoilated in a screen for silencing factors of the mating
locus and later found to extend lifespan in S. cerevisiae. deletion of this gene was
reported to block the lifespan extension by CR - Answer-Sir2
caloric restriction can affect lifespan in two ways... - Answer-1. change respiration
rate (increase NAD+)
2. activate Nampt
what are sirtuins? - Answer-NAD+-dependent protein deacetylases
___ is the rate-limited enzyme of the NAM--> NAD+ resynthesis pathway and
regulation of Nampt activity by CR can lead to SIRT1 activation - Answer-Nampt
WITH COMPLETE ANSWERS
___ is the predominant zeitgeber for the SCN clock while clocks in peripheral tissues
can be entrained by ___ - Answer-light; food
nutrient sensing by nuclear hormone receptors can alter circadian rhythms by
changing expression of clock genes
ex) Rev-erb (____ ) and Bmail (____) - Answer-PPAR gamma & alpha
PPAR alpha
peripheral clocks regulate metabolism in part through circadian expression of ___
and ____ - Answer-nuclear hormone receptors and key metabolic hormones
the majority (70%) of the body's 3-5g of iron is utilized by ____ cells - Answer-
erythroid
nonheme iron uptake - Answer-1. ferric --> ferrous
2. reductase duodenal cytochrome b
3. transport across the apical membrane via DMT1 (divalent metal transporter 1)
4. export of Fe2+ by basolateral transporter ferroportin
5. hephaestin converts back to Fe3+ on plasma membrane
6. circulating Fe3+ bound by plasma iron carrier transferrin; delivers iron to erythroid
bone marrow and other tissues
7. binds to transferrin receptor and undergoes endocytosis
8. iron release accomplished by acidification of endosome to pH~5.5
9. iron reduced by the STEAP family of ferrireductases and transported out of the
late endosome by DMT1 into the cytoplasm
10. when trasnferrin pool becomes saturated, non-transferrin bound iron can also
enter cells directly through DMT1)
11. some stored in ferritin as a buffer
12. Fe3+ to Fe2+ to be released into circulation
mechanisms to prevent iron overload - Answer-1. transferrin-bound iron can come
together with HFE and interact with TfR2 on hepatocytes, triggering signaling
cascade that leads to the secretion of Hepcidin
2. Hepcidin can be sensed by intestinal cells (and macrophages) and cause
internalizationa nd degradation of ferroportin, thus trapping dietary iron in the
intestine
-any mutations in these lead to iron overload disease
pro-inflammatory cytokine ___ causes, through activation of hepatic IL-6 receptors, a
large increase in hepcidin leading to suppression of absorption and reduced
circulating iron levels - Answer-IL6
symptoms of ACD (anemia of chronic disease) - Answer--feeling weak or tired
-headache
-paleness
,-shortness of breath
____ is a functional aconitase, interconverting citrate and isocitrate in the cytosol.
this contains a 4Fe-4S cluster in its active site - Answer-IRP1
the iron-sulfur cluster IRP1 is readily destabilized by _____. if the iron-sulfutre cluster
is not replaced, IRP1 assumes a IRE binding conformation - Answer-oxidants
what is important for IRP binding? - Answer-the GUGAC loop and unpaired C in the
stem of IRE
in iron starvation, what will be active? - Answer-IRP
risk of developing T2DM in men and women with elevated serum ferritin levels are
____ fold as high as in persons with normal iron levels approaching the risk
engendered by obesity. reason? - Answer-5 to 3.6
reason: unclear, but may be due to altered levels of adipokines
iron deficiency =
iron overload = - Answer-anemia
heart and liver failure (hereditary hemochromatosis and transfusional iron overload)
mutations in the hepcidin pathway lead to _______ - Answer-hereditary
hemochromatosis
T/F : inflammmation can cause decrease hepcidin secretion and in the case of
chronic inflammation can result in ACD - Answer-FALSE - increase hepcidin, so
leads to buildup of iron
T/F: mutations in IREs can prevent IRP binding and lead to aberrant protein
expression - Answer-True
T/F: pathological and dietary iron deficiency increases T2Dm susceptibility - Answer-
False; iron overload
an adult on a low-cholesterol diet typically synthesizes about __ mg of cholesterol
per day - Answer-800
which terminus of SREBP (transcription factor) binds to ___, which acts as a sterol
sensor - Answer-C-termus; SCAP
in sterol depleted cells, Scap escorts SREBP to the Golgi by binding to ___ (a
component of the ___ protein coat) - Answer-Sec 24, CopII
in the Golgi, SREBP is proteolytically processed by two proteases (___ and ___) to
generate the nuclear form that activates genes for cholesterol synthesis and uptake -
Answer-S1P and S2P
binding of cholesterol to SCAP's sterol-sensing domain causes conformational
change that prevents interactions with the ___ proteins - Answer-CopII
, Sterol mediated ER retention of Scap/SREBP is enhanced by binding to the ER
resident protein __ - Answer-Insig
___ is an SREBP target gene, thus SREBP induces the (mRNA) expression of its
own negative regulator - Answer-Insig1
when cells are deprived of sterols, Insig is rapidly ____ and ___ by proteasomes -
Answer-ubiquitinated and degraded
depletion of cholesterol leads to(6) - Answer-- dissociation of SREBP/Scap from
Insig
-Insig ubiquitination and degradation
-SREBP/Scap binding to CopII proteins and translocation to the Golgi
-SREBP processing and translocation to the nucleus
-activation of SREBP target genes increasing cholesterol biosynthesis and uptake
-increased Insig synthesis but rapid degradation keeps levels low unless sufficient
cholesterol accumulates to bind Scap
what is "convergent inhibition" - Answer-newly supplied cholesterol and newly
synthesized Insig when you block SREBP
altered autophagic degradation of glycogen stores may underlie the basis of different
muscle disorders such as ___, an X-linked vascular myopaty - Answer-Danon
disease
autophagy can indirectly contribute to glucose metabolismm by modulating ____ and
function as macroautophagy is required to prevent the accumulation of dysfunctional
mitochondria that can damage the cells through the generation of _____ - Answer-
pancreatic B-cell mass
reactive oxygen species
starvation activates macroautophagy in part through inhibition of ____ via decreased
___ and active ____ - Answer-mTORCI; AA and active AMPK
alterations in autophagy are associated with ___ and ____ - Answer-metabolic
disorders and aging
the yeast protein ____ was isoilated in a screen for silencing factors of the mating
locus and later found to extend lifespan in S. cerevisiae. deletion of this gene was
reported to block the lifespan extension by CR - Answer-Sir2
caloric restriction can affect lifespan in two ways... - Answer-1. change respiration
rate (increase NAD+)
2. activate Nampt
what are sirtuins? - Answer-NAD+-dependent protein deacetylases
___ is the rate-limited enzyme of the NAM--> NAD+ resynthesis pathway and
regulation of Nampt activity by CR can lead to SIRT1 activation - Answer-Nampt
