Chemistry, Metabolism,and Clinical disorders of Lipids
1.A 35-year-old woman presents with severe,Sharp epigastric abdominal
pain that radiates to Her back and with nausea and vomiting. Laboratory
results indicate a serum triglyceride level Of 5000 mg/dL. She is diagnosed
with pancreatitis.To form triacylglycerol from Diacylglycerol, which of the
following compounds is also required?
(A)Glycerol
(B)Glycerol 3-phosphate
(C)Fatty acyl CoA
(D) Acetyl CoA
(E)Malonyl CoAl
Key:C
Explanation:Triacylglycerol is formed when a diacylglycerol reacts with
a fatty acyl CoA.
Source:Lehninger AL. Biochemistry. 8th ed. New York: W.W.
Norton & Company; 2019.
2.A 40-year-old woman presents with chronic diarrhea and weight loss
after undergoing surgical resection of part of her small intestine. She is
diagnosed with short bowel syndrome and is unable to absorb fats
properly. As a result, her body is mobilizing long-chain fatty acids from
her adipose tissue to generate energy. What is the initiating substrate
for fatty acid oxidation in this scenario?”
(A) Acetyl-CoA
(B) Fatty acyl-CoA
(C) Carnitine
(D)long chain Fatty acid
(E)beta hydroxyacyl CoA
Key:B
Explanation:Fatty acyl CoA undergoes b-oxidation in a spiral involving
four steps.
Source:Lehninger AL. Biochemistry. 8th ed. New York: W.W.
Norton & Company; 2019.
3.A 45-year-old man presents with multiple gunshot wounds to the
abdomen and requires emergency surgery. After undergoing a
jejunectomy and colectomy, he is started on total parenteral nutrition
(TPN). Which of the following components is essential for inclusion in
his TPN?
(A) Palmitate
(B) Linoleate
(C) Phosphatidic acid
(D) Glycerol
(E) Glucose
Key:B
Explanation:Linoleate and a-linolenate are the essential fatty acids
required in the human diet.
Source:Lehninger AL. Biochemistry. 8th ed. New York: W.W.
Norton & Company; 2019.
4.A 16-year-old girl presents with extreme slenderness, with a body
weight 35% below expected. She has a distorted body image and
severely restricts her food intake, leading to a diagnosis of anorexia
nervosa. As her body tries to adapt to the lack of nutrients, it begins to
break down fatty acids for energy. Which of the following is the
activated form of fatty acids that can be transported into the
mitochondria for oxidation?
(A) Fatty acid
(B) Fatty acyl CoA
(C) CoA
(D) Carnitine
(E) Acetyl CoA
Key:B
Explanation:Long-chain fatty acids are activated, in a reaction requiring
ATP and CoA, to a Fatty acyl CoA.
Source:Lehninger AL. Biochemistry. 8th ed. New York: W.W.
Norton & Company; 2019.
5.A 50-year-old man presents with symptoms of coronary artery
disease, including chest pain and shortness of breath. A coronary
angiogram reveals a significant blockage in one of his coronary
arteries, and he is diagnosed with ischemic heart disease. High serum
HDL levels are protective against the development of atherosclerosis
because HDL:
(A) Increases LDL receptor expression
(B) Decreases LDL receptor expression
(C) Brings cholesterol esters back to the liver
(D) Inhibits HMG-CoA reductase
(E) Increases VLDL production
Key :C
Explanation:HDL is known as the ‘‘good’’ lipoprotein particle because
HDL scavenges cholesterol from the periphery (from cell membranes
and from other lipoproteins) and brings cholesterol esters back to the
liver, where they can be converted to and excreted as bile salts.
Source:Lehninger AL. Biochemistry. 8th ed. New York: W.W. Norton &
Company; 2019.
6.A 45-year-old man presents with an LDL serum level of 420
(recommended level is <130) and a triglyceride level of 180
(recommended level is <150). He is diagnosed with type II familial
hypercholesterolemia. In this disorder, a mutated LDL receptor is
formed, such that it cannot bind to LDL. Which of the following would
result?
(A) Cellular HMG-CoA reductase activity is inhibited
(B) The triglycerides in chylomicrons cannot be degraded
(C) The VLDL level in the serum decreases
(D) The HDL level in the serum increases
(E) Cellular HMG-CoA reductase activity is not inhibited
Key: E
Explanation:In type II familial hypercholesterolemia, the mutated LDL
receptor cannot bind to LDL, leading to a buildup of LDL in the
bloodstream. As a result, the cellular HMG-CoA reductase activity is not
inhibited, and cholesterol synthesis continues unabated. This leads to
increased cholesterol production in the liver, which contributes to the
high LDL levels.
Source:Lehninger AL. Biochemistry. 8th ed. New York: W.W.
Norton & Company; 2019.
7.A 30-year-old man presents with a history of recurrent pancreatitis
and is found to have a low level of HDL cholesterol. He is diagnosed
with LCAT deficiency. LCAT is involved in which of the following
processes?
(A) Converting cholesterol to cholesterol esters
(B) The transfer of cholesterol esters from HDL to other lipoproteins
(C) Endocytosis of HDL particles into hepatocytes
(D) Hydrolysis of HDL
(E) Synthesis of apoA-I
Key:A
Explanation:LCAT converts cholesterol to cholesterol esters, which
accumulate in the core Of HDL. This is an important part of reverse
cholesterol transport.
Source:Lehninger AL. Biochemistry. 8th ed. New York: W.W.
Norton & Company; 2019.
8.A 12-year-old boy presents with fatigue, polydipsia, polyuria, and
polyphagia. A random Glucose measurement shows a glucose level of
350 mg/dL in his serum. He is diagnosed with Type 1 diabetes mellitus,
a disease characterized By a deficiency of insulin. Which one of the
following is most likely occurring in this patient?
(A)Increased fatty acid synthesis from glucose In liver
(B)Decreased conversion of fatty acids to keTone bodies
(C)Increased stores of triacylglycerol in adipose tissue
(D) Increased production of acetone
(E)Chronic pancreatitis
Key:D
Explanation:A decreased insulin-to-glucagon ratio leads to a
decrease in fatty acid synthesis and an increase in adipose
triacylglycerol degradation, leading to fatty acid release into the
circulation. The liver takes up the fatty acids, and within the
mitochondria, fatty acids undergo b-oxidation. As acetyl CoA
accumulates, the ketone bodies, acetoacetate and b-
hydroxybutyrate, are formed and are released into the circulation.
Source:Lehninger AL. Biochemistry. 8th ed. New York: W.W.
Norton & Company; 2019.
9.An infant is born prematurely at 28 weeks and increasingly has
significant difficulty Breathing, taking rapid breaths with intercostal
Retractions. The child soon becomes cyanotic.
He is diagnosed with respiratory distress syndrome
due to a deficiency of surfactant. Which
Of the following is the phospholipid in highest
Concentration in surfactant?
(A)Dipalmitoyl phosphatidylcholine
(B)Dipalmitoyl phosphatidylethanolamine
(C)Dipalmitoyl phosphatidylglycerol
(D) Dipalmitoyl phosphatidylinositol
(E)Dipalmitoyl phosphatidylserine
Key:A
Explanation:Dipalmitoyl phosphatidylcholine (DPPC), also called
lecithin, is the major phospholipid in surfactant.
Source:Lehninger AL. Biochemistry. 8th ed. New York:
W.W. Norton & Company; 2019.
10.A 2-year-old boy is failing to meet age-appropriate
milestones, including a progressive difficulty in walking. An
abnormally low level of hexosaminidase A is found in his cells,
causing accumulation of GM2 ganglioside in neurons.
Unfortunately, he dies 5 years later. Which one of the following is
the most likely diagnosis for this disorder?
(A) Fabry disease
(B) Gaucher disease
(C) Niemann-Pick disease
(D) Tay-Sachs disease
(E) Metachromatic leukodystrophy
Key:E
Explanation:Metachromatic leukodystrophy is due to a deficiency
in arylsulfatase A, a lysosomal enzyme that degrades sulfated
glycolipids. These sulfatide compounds accumulate in neural
tissue, causing demyelination of central nervous system and
peripheral nerves, with resultant loss of cognitive and motor
functions.
Source:Lehninger AL. Biochemistry. 8th ed. New York:
W.W. Norton & Company; 2019.
11.A male infant with 3-beta hydroxylase deficiency is born with
ambiguous genitalia and severe salt wasting from lack of
androgens and aldosterone, respectively. Testosterone, a major
androgen, is produced by which of the following reactions?
(A) Oxidation of the A ring of pregnenolone
(B) Removal of the side chain of the D ring of progesterone
(C) Aromatization of the A ring of estradiol
(D) Cleavage of the side chain of progesterone
(E) Hydroxylation of the C21 position of progesterone
Key: B
Explanation:3-b-Hydroxylase deficiency is a disease resulting in
decreased production of aldosterone, cortisol, and androgens (3-
b-hydroxylase is required for production of all three type of
steroids). Male infants manifest with ambiguous genitalia (owing
to lack of androgens and testosterone), and both males and
females show salt wasting (owing to lack of
aldosterone).Testosterone is produced only by the removal of the
side chain of the D ring of progesterone.
Source:Lehninger AL. Biochemistry. 8th ed. New York:
W.W. Norton & Company; 2019.
12.A 6-month-old infant presents with muscular weakness that is
progressing to paralysis. Examination of the back of the eye
shows a cherry-red spot on the macula. An abnormally low level
of hexosaminidase A is present, causing deposition of certain
gangliosides in neurons. The accumulating material in this
disorder is which of the following?
(A) GM1
(B) GM2
(C) GM3
(D) GD1a
(E) GT1b
Key:B
Explanation:This patient has either Tay-Sachs or Sandoff disease.
Patients with these diseases have a deficiency of hexosaminidase
A (Tay-Sachs), or hexosaminidase A and B (Sand-off Activity)
resulting in the buildup of GM2 in neurons, which can result in
neurodegeneration and early death.
Source:Lehninger AL. Biochemistry. 8th ed. New York:
W.W. Norton & Company; 2019.
13.A 40-year-old man presents with chest pain that radiates to
his left jaw and shoulder. He is diagnosed with a myocardial
infarction and is prescribed a statin medication. Statins are
competitive inhibitors of HMG-CoA reductase, which converts
HMG-CoA to which of the following?
(A) Mevalonate
(B) Isopentenyl pyrophosphate
(C) Geranyl pyrophosphate
(D) Squalene
(E) Cholesterol
Key:A
Explanation:HMG-CoA reductase converts HMG-CoA to
mevalonate, using two NADPH molecules.
Source:Lehninger AL. Biochemistry. 8th ed. New York:
W.W. Norton & Company; 2019.
14.The major carriers of triacylglycerols are which of the
following?
(A)Chylomicrons and VLDL
(B)IDL and LDL
(C)VLDL and LDL
(D) HDL and LDL
(E)Chylomicrons and LDL
Key:A
Explanation:The major carriers of triacylglycerols are
chylomicrons (synthesized in the intestine from dietary fat) and
VLDL (synthesized in the liver).
Sources:Lehninger AL. Biochemistry. 8th ed. New York:
W.W. Norton & Company; 2019.
Murray RK, Bender DA, Botham KM, Kennelly PJ, Rodwell
VW, Weil PA. Harper’s Illustrated Biochemistry. 31st ed.
New York: McGraw-Hill Education; 2018.
Short Essay Questions
Q1.
An 18-year-old woman presents in Mayo hospital OPD with
xanthomas on her eyelids and is found to have a rare genetic
deficiency of lipoprotein lipase.
a.What is likely diagnosis?(1)
b.Justify the clinical symptoms with underlying mechanism of
disease.(3)
c.In which cell or tissue does triacylgycerol packaging into
chylomicrons occur?(1)
Key:
a.Type 1 hyperlipidemia
b.Lipoprotein lipase (LPL) is absent,the enzyme responsible for
breaking down triglycerides in lipoproteins is not functioning.
This leads to a buildup of triglyceride-rich lipoproteins in the
blood, causing hypertriglyceridemia.The body’s ability to
metabolize triglycerides is severely impaired, leading to an
accumulation of chylomicrons and very-low-density lipoproteins
(VLDL) in the blood. This can cause xanthomas, pancreatitis,
hepatosplenomegaly and lipemia retinalis.
c.Intestinal epithelial cells are the site of chylomicron formation,
and dietary TAGs are bound to apoproteins and other lipids to
form chylomicrons .
Source:Lehninger AL. Biochemistry. 8th ed. New York:
W.W. Norton & Company; 2019.
Q2.
An 8-year-old Ashkenazi Jewish girl presents with an enlarged
liver and spleen, low white and red blood cell counts, bone pain,
and bruising on her body.
1.What is diagnosis?(1)
2.Give the biochemical defect in this disease.(2)
3.What is the pattern of inheritance of this disease?(2)
Key:
a.Gaucher disease
b.Patients with Gaucher disease have a deficiency of b-
glucocerebrosidase,resulting in glucocerebroside accumulation in
the lysosomes of cells of the liver, spleen, and bone marrow.
Formation of Gaucher cells, which are enlarged macrophages
filled with glucocerebroside occurs.This leads to
hepatosplenomegaly,anemia, thrombocytopenia,and
osteoporosis.
c.Gaucher disease is an autosomal recessive disorder, so a
person must inherit two copies of the mutated gene (one from
each parent) to develop the condition.This pattern of inheritance
applies to all forms of Gaucher disease, including Type 1, Type 2,
and Type 3.
Source:Lehninger AL. Biochemistry. 8th ed. New York:
W.W. Norton & Company; 2019.
