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Name:________________
UCB ID#:________________
NST 160, Spring 2008
Midterm Exam I
Select all correct answers (5 points per question)
Correct answers in bold
1. The “metabolic syndrome”
A. Is associated with no worse cardiovascular risk than having high blood
pressure, obesity or high blood triglyceride levels alone
B. May be explained by the hypothesis that insulin resistance promotes
other cardiovascular risk factors, such as hypertension
C. Is irreversible once it is present
D. Requires obesity or increased waist circumference to be diagnosed
E. May include a pro-inflammatory state, abnormal blood lipid levels
and a tendency for blood clotting
2. Your friend is discouraged; he went on a diet (1600 Kcal/day) because he was
overweight (100 kg) and he has lost 10 kg, but has not lost any weight for a month
and feels hungry. You
A. Tell him to be patient; the weight loss will pick-up again if he sticks to the
diet that originally got him to lose weight
B. Encourage him to walk 4-5 miles a day, if he wants to continue to lose
weight and keep it off
C. Explain that he would have to eat even less than he is doing now, to
lose more weight by dieting alone, because his metabolism has
probably slowed down
D. Explain that his body has a set point and wants to be overweight, so he
will never be able to lose weight and should just accept that fact
E. Explain that any exercise that increases his muscle mass will make it
easier to lose weight or keep is off, because extra muscle burns
calories, even when resting
3. Body fat stores
A. Are all the same, in terms of lipolytic rate, regardless of anatomic location
or adipocyte size
B. When there is spill over from subcutaneous fat depots to organs like
liver muscle and pancreas, can lead to problems
C. Are increased by certain drugs like glitazones (PPAR gamma agonists),
which thereby worsen insulin resistance or diabetic control
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D. Are associated with optimal health when as reduced in mass as possible,
as in lipoatrophy
E. Exhibit a fixed cell number in adults, so that changes in fat mass can only
result in changes in adipocyte size, not number
4. High-carbohydrate, low-fat diets can have a number of metabolic consequences,
A. Including high blood triglyceride levels, especially if the carbohydrate
includes a large proportion of simple sugars
B. Promotion of diabetes mellitus by worsening insulin resistance
C. A modest weight loss, which tends to mitigate initial elevations in
blood triglycerides over time
D. A clear increase in risk of heart disease and stroke, compared to high fat
diets
E. A tendency to lower LDL cholesterol concentrations, compared to
high fat diets
5. Metabolic “fitness” in a person
A. Is incompatible with high amounts of body fat, and is, by definition, not
present if an individual is obese
B. Relates to the person’s capacity to do aerobic work
C. Tends to be associated with reduced visceral fat stores, as in Sumowrestlers
D. Is a strong negative risk factor for cardiovascular disease at all levels
of body weight
E. Is a genetic characteristic and remains relatively constant throughout life,
independent of activity level
6. Diseases associated with overweight or obesity include,
A. Fatty liver
B. Colon cancer
C. Parkinson’s disease
D. Ovarian dysfunction
E. Auto-immune diseases
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Name:________________
Short answer questions (10 points each)
1. Compare the interpretation, degree of interpretative certainty and limitations of
epidemiologic studies, retrospective case-control studies, uncontrolled prospective trials
and prospective randomized controlled trials (PRCTs). Be brief (1-2 sentences on each).
Why do you think PRCTs are required for approval of drugs?
Epi- hypoth generating; not definitive
Retro: Confounding factors/not definitive
Uncontrolled: selection bias
PRCT: Highest level- therefore required for drug approval
Etc.
2. An adipocyte enzyme involved in the adipose triglyceride synthesis pathway is
found to be highly expressed in obese rodents and people. A knock-out mouse is not
protected from obesity, however, and an inhibitor of the protein when given to obese
humans results in no weight loss. Briefly discuss these findings and provide some
possible explanations in context of the metabolic control of complex networks.
Hi expr not equal to causal role
Lack of effect of ko or inhibitor possibly interpr by adaptation OR no
primary role in obesity
General point: obesity is complex disorder, thus unpredictable control, so
the effects of any individual enzyme or node on global phenotype is nearly always
uncertain
Etc.
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Section 2:
1) For 2 points
True or False (T or F)
Only the GI tract senses nutrients
Nutrient concentrations can be sensed by many different cellular mechanisms
Certain GPCRs can sense amino acid concentrations
Amino acid sensing is not involved in taste perception
F
T
T
F
2) For 3 points
What is the logical order of the following events (number 1 through 5)?
Cellular cAMP levels rise
5
GDP bound to Gs is replaced by GTP
3
Receptor binds to heterotrimeric G protein 2
Gsbinds to adenylated cyclase
4
Ligand binds to GPCR
1
3) For 3 points
Would a meal without essential amino acids stimulate protein synthesis?
Explain (as succinctly as possible):
No, the essential AA leucine is required for effects on translation
4) For 6 points
Explain in the fewest words possible how a lack of essential amino acids alters the
activity of the translation initiation factors eIF2 and eIF4E:
lack of essential AAs leads to
- eIF2 phosphorylation, which inhibits GEF activity of eIF2B, and
accumulation of inactive GDP-bound eIF2
lack of mTOR activity preventing phosphorylation of 4E-BP thus
trapping/inactivating eIF4E
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Name:________________
5) For 3 points
AMPK senses cellular energy availability by gauging ATP to AMP ratios. Why is this
more sensitive then comparing the ratio of ATP to ADP?
Due to the action of adenylated kinase 2 ADPs are converted into ATP and AMP
thus the AMP/ATP ratio varies with the square of the ADP/ATP ratio
6) For 3 points
Explain (succinctly) one mechanism by which AMPK can enhance the uptake and
oxidation of fatty acids by mitochondria:
AMPK phosphorylates and inactivates ACC. Inhibition of ACC decreases the
concentration of malonyl CoA. Malonyl CoA inhibits CPT1 activity, so a decrease in
malonyl CoA will allow for more active CPT1 leading to more fatty acid oxidation
7) For 2 points
Which of the following signals can alter mTOR activity (mark all that apply)?
Insulin
X
Leucine
X
DNA damage
O
AMPK activation
X
8) For 3 points
Name two mechanisms by which iron regulatory proteins can affect the abundance of
proteins with iron response elements in their mRNAs:
A) Inhibition of translation
B) mRNA stabilization
9) For 2 points
Fill in the blanks
Iron starvation inhibits ferritin expression and increases transferrin receptor levels.
10) For 2 points
Which of the following metabolites does not bind to a nuclear hormone receptor (mark
all that apply):
Fatty acids
O
Retinoic Acid
O
Amino Acids
X
Bile Acids
O
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11) For 2 points
Pharmacological activation of peroxisome proliferator receptor alpha mimics what
physiological response (mark all that apply):
Starvation
X
Hypothermia
O
Hyperglycemia
O
Hybernation
O
12) For 4 points
Mr. Maxomi (not a real person) was born with a mutation that results in increased
peroxisome proliferator receptor delta expression. Do you think this would increase or
decrease his chances of winning the Boston marathon? Explain your answer in as few
words as possible.
Increase, as PPAR delta activation increases muscle FFA oxidation and a switch to
slow twich (type I) muscle fibers that are needed for endurance
13) For 3 points
Both the anorexic alpha-melanocyte stimulating hormone and the orexigenic Agoutirelated Peptide act through the same melanocortin receptor in the brain. How is that
possible (explain as succinctly as possible)?
Alpha-MSH is an MC-4R agonist while AgRP is an inverse agonist
14) For 2 points
True or False (T or F)
Leptin is a hormone secreted by adipocytes
T
A rise in leptin has orexigenic effects
F
Leptin stimulates POMC/CART neurons
T
Leptin secretion is regulated through the hexosamine biosynthetic pathway T
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Name:________________
15) For 10 points
Solve the crossword puzzle
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