Biochemistry Spotters for Medics/TITLE

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Biochemistry Spotters

Biochemistry for Medics Biochemistry For
Medics
11/18/2012

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Compiled from-BIOCHEMISTRY FOR MEDICS
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Biochemistry For Medics 11/18/2012

Case study
A morbidly obese woman decides to see her physician to begin
a weight loss program. He tells her that diet and exercise play
an essential role in her program. She is concerned that she
does not have time to devote to exercise and wants to know if
there is any pharmacologic treatment for her. The physician
decides to start her on Orlistat which directly inhibits
absorption of fats. Which of the following steps is
directly inhibited by Orlistat ?
A) bile salt formation
B) Micelle formation
C) Pancreatic and gastric lipase
D) Absorption of Free fatty acids
E) Chylomicron formation

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Answer to case study
C)-Orlistat inhibits gastric and pancreatic
lipases, preventing the digestion and absorption of fats.
The normal sequence of digestion is that triglycerides are
emulsified by bile salts. These are then acted on by
lipases. The product of digestion are absorbed and
reesterified in the intestinal mucosal cells to form
triglycerides which are packed in the chylomicrons for
transportation out to the peripheral cells for utilization.

Under the effect of orlistat triglycerides are left
undigested and unabsorbed, resulting in bulky stools.
Over a period of time, orlistat therapy can induce
deficiency of fat soluble vitamins.

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Case study
A young man with normocytic anemia, jaundice, and
splenomegaly was diagnosed as having RBC pyruvate
kinase deficiency after a peripheral blood smear showed
spiculated cells. Since in this patient pyruvate kinase is
abnormal not only is less pyruvate made but
intermediates above pyruvate in the glycolytic pathway
build up slowing the pathway. Which of the following
products may not be made in the appropriate
amounts in the RBC because of the deficiency of
pyruvate?
A) Glucose
B) Oxaloacetate
C) Acetyl-CoA
D) Lactate

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D)- The RBCs have no mitochondria so glucose
cannot be made from pyruvate or acetyl-CoA or
Oxaloacetate.
The RBCs do have lactate
dehydrogenase and conversion to lactate
depends on pyruvate levels.

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Case study
Which of the following
complications is less
likely to occur in type II
diabetics, as opposed to
type I diabetics?
A) Retinopathy
B) Weight gain
C) Cardiovascular disease
D) Hypoglycemic coma

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D)- Hypoglycemia is a common complication
associated with over supplementation of type I
diabetics with insulin. This is less common in type II
diabetics, because insulin therapy generally occurs
only in the later stages of the pathogenesis of this
disease. Retinopathy, cardiovascular disease, and
neuropathy are common complications associated
with both forms of diabetes mellitus. In contrast to
type I diabetics, type II diabetics tend to be
overweight. Whether weight gain is a cause or
consequence of disease progression is under current
debate.

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Case study
After excessive drinking over
an extended period of time
while eating poorly, a middle-
aged man is admitted to the
hospital with “high output”
heart failure. Which of the
following enzymes is most
likely inhibited?
A) Aconitase
B) Citrate synthase
C) Isocitrate dehydrogenase
D) α-Ketoglutarate
dehydrogenase
E) Succinate thiokinase

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D)-This patient has exhibited symptoms of beri
beri heart disease, which is a result of a
nutritional deficiency in vitamin B1 (thiamine).
The active form of the vitamin, thiamine
pyrophosphate, is a required cofactor for α-
ketoglutarate dehydrogenase.

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Case study
Which of the following is least
likely to contribute to the
hyperglycemia associated with
uncontrolled type I diabetes?

A) Decreased skeletal muscle
glucose uptake
B) Decreased adipose lipogenesis
C) Increased adipose lipolysis
D) Increased hepatic
gluconeogenesis
E) Increased skeletal muscle
glycogenolysis

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E) Unlike the liver, skeletal muscle cannot export glucose into
the circulation.
Once glucose enters the myocyte, it is destined for use by
that cell. Thus, intramyocellular glycogen is used as a fuel
source by skeletal muscle and therefore cannot contribute to
the hyperglycemia observed in uncontrolled type I diabetes.

In contrast decreased insulin mediated glucose utilization by
skeletal muscle and adipose will contribute to hyperglycemia,
as will decreased insulin-mediated suppression of hepatic
glucose output. Decreased insulin-mediated suppression of
lipolysis will indirectly contribute to hyperglycemia, by
providing alterative, nonglucose, fuels (fatty acids and ketone
bodies) or organs such as skeletal muscle and the liver.

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Case study
A 3-year-old Caucasian female presents with chronic
diarrhea and a failure to thrive. Stools were oily.
History reveals that she was breastfed
and had no problems until she was weaned. Which
of the enzymes would be expected to be
deficient following stimulation with
secretin?
A) Cholesteryl esterase
B) Gastric lipase
C) Hormone sensitive lipase
D) Lipoprotein lipase
E) Pancreatic lipase

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E) Neither hormone sensitive lipase nor
lipoprotein lipase is a digestive enzyme. The
patient’s symptoms are consistent with an
inability to absorb triglycerides, which would
eliminate Cholesteryl esterase from
consideration. Since the patient did not have any
problem while being breast-fed, then the most
likely enzyme to be deficient is pancreatic lipase,
since gastric lipase is most active on short chain
triglycerides, such as those that are found in
breast milk.

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Case study
A gall stone that blocked the
upper part of the bile duct would
cause increase in which of the
followings ?
A) The excretion of fats in the
feces
B) Formation of chylomicrons
C) Excretion of bile salts
D) Conjugation of bile acids
E) Recycling of bile salts

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A) The right answer is excretion of excess fats in
the feces, In this situation, bile salts cannot enter
the digestive tract, therefore recycling and
excretion of bile salts, digestion of fats, and
formation of chylomicrons are decreased.
As a consequence fats in the feces are increased
(Steatorrhea).

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Case study
A young infant, who was nourished with a synthetic
formula, had a sugar in the blood and urine. This
compound gave a positive reducing sugar test but was
negative when measured with glucose oxidase(specific
test for detection or estimation of Glucose). Treatment of
blood and urine with acid (which cleaves glycosidic
bonds) did not increase the amount of reducing sugar
measured. Which of the following compounds is
most likely to be present in this infant's blood
and urine ?
A) Glucose
B) Fructose
C) Maltose
D) Sorbitol
E) Lactose

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B) The right answer is fructose. Glucose can
not be there since specific test is negative.
Sorbitol is non reactive to reduction test.
Maltose and lactose would have caused
increase in the amount of reducing sugar
upon acid hydrolysis.
Hence it is fructose which is reducing in
nature nut non reactive to glucose oxidase.

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Case study
A 71-year-old man had a 3 week history
of weakness, polyuria, intense thirst,
difficulty in speaking and understanding
commands, staggering walk, confusion
and a weight loss of 10 kgs. For one
month he took 200,000 units of vitamin
D each day because he had severe
osteoarthritis. His plasma calcium was
3.38 mmol/L(13.5 mg/dl)
What is the most probable
diagnosis?

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It is a case of vitamin D toxicity. Usually, vitamin D toxicity
results from taking excessive amounts. Because synthesis of
1,25(OH)2D (the most active metabolite of vitamin D) is tightly
regulated, vitamin D toxicity usually occurs only if excessive
doses (prescription or megavitamin) are taken.

Marked hypercalcemia commonly causes symptoms. Anorexia,
nausea, and vomiting can develop, often followed by polyuria,
polydipsia, weakness, nervousness, pruritus, and eventually
renal failure. Proteinuria, urinary casts, azotemia, and metastatic
calcifications (particularly in the kidneys) can develop.

Diagnosis is typically based on elevated blood levels of 25(OH)D.
Treatment consists of stopping vitamin D, restricting dietary Ca,
restoring intravascular volume deficits, and, if toxicity is severe,
giving corticosteroids or bisphosphonates.

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Case study
A 40 -year-old woman presented with
chest pain. Her blood biochemistry report
did not reveal significant changes and ECG
was also normal. Her family history was
positive for IHD. She was kept under
observation and was discharged later after
a few hours. She was advised to start a low
dose of Aspirin. Aspirin is considered
cardio protective, since it inhibits cyclo -
oxygenase (COX) enzyme.
COX is required for the production of
which of these ?
A) Thromboxane from arachidonic acid
B) Leukotrienes from Arachidonic acid
C) Phospholipids from Arachidonic acid
D) Arachidonic acid from Linoleic acid
E) Linolenic acid from Arachidonic acid

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A) Aspirin irreversibly acetylates cyclo-oxygenase-1 of
platelets and inhibits the enzyme so that Thromboxane
(TxA2) is not formed. So there is no vasoconstriction and
no platelet aggregation and hence the thrombus
formation is prevented.
At the same time Aspirin also inhibits production of
Prostacyclin (PGI2) by endothelial cells, which prevents
platelet aggregation and produces vasodilatation. But
unlike platelets, the endothelial cells regenerate cyclo-
oxygenase within a few hours. Thus the overall balance
shifts towards prevention of thrombus formation by
promoting the Prostacyclin formation. Aspirin is
clinically used for the prevention and management of
Angina. Myocardial infarction, Stroke and Transient
Ischaemic attacks (TIA).

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Case study
A 23-year-old, boxing contender
presents with assorted metabolic
disorder , most notably ketosis.
During the history and physical
examination, he describes his
training regimen, involves consuming
a dozen raw eggs a day for protein.
Raw eggs contain a protein called
Avidin, with an extremely high
affinity for a cofactor required for the
propionyl co A carboxylase and
Acetyl co A carboxylase. Name the
cofactor which gets deficient by
consumption of raw eggs.

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The right answer is Biotin. Egg white contains
Avidin, that binds with high affinity to Biotin. Biotin
is the cofactor required for conversion of Propionyl
co A to D-Methyl malonyl co A and also for the
conversion of Acetyl co A to Malonyl co A.
Consumption of raw eggs promotes formation of
Avidin- Biotin complex causing Biotin deficiency,
known as Egg white injury. The said complex is not
formed if the same number of cooked eggs are
ingested, since cooking causes denaturation of
Avidin and that loses the ability to bind with biotin.

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Case study
An infant is born with a high forehead,
abnormal eye folds, and deformed ear lobes.
He shows little muscle tone and movement.
After multiple tests, he is diagnosed with
Zellweger syndrome, a disorder cause by
malformation of peroxisomes.
Which of the following is expected to
be high in concentration in brain tissue
of the affected individual ?
A) Ketone bodies
B) Lactate
C) Cholesterol
D) Very long chain fatty acids

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D) The right answer is "Very long chain fatty
acids". Very long chain fatty acids are first
trimmed in the peroxisomes till the length of C16
or C18, then they are transported to
mitochondria in the conventional way though
carnitine shuttle to be oxidized completely by
beta oxidation.
In Zellweger syndrome the Peroxisomal
trimming is impaired, thus VLFA accumulate in
brain and blood of affected patients.

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Case study
An 18 month-old- child is left
unattended while in the
kitchen and ingests a small
portion of rat poison found in
the cupboard found under
the sink. The ingredient
fluoroacetate reacts with
Oxaloacetate to form
fluorocitrate. Which
pathway of the body is
inhibited by this poison ?

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TCA Cycle is inhibited by Fluoroacetate
Fluoroacetate first gets converted to
Fluoroacetyl coA then condenses with
Oxaloacetate to get converted to Fluoro citrate to
inhibit Aconitase enzyme of TCA cycle.
It is an example of suicidal inhibition.

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Spot Question
High carbohydrate ingestion leads to obesity,
What are the two most important causes ?

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Answer to spot question
Excessive carbohydrate consumption leads to obesity-
1) Excess glucose available- two main pathways of
glucose utilization provide precursors for lipogenesis
A) HMP pathway- Provides NADPH for reductive
biosynthesis
B) Glycolysis- Provides Acetyl co A and Glycerol-3-p
a) Excess of Pyruvate from glucose- Excess of Acetyl co A
- Excessive fatty acid synthesis
b) Excess of glycerol-3-p - available from Dihydroxy
acetone Phosphate
Esterification of Glycerol-3-P with fatty acids to form
Triglycerides- Increased adipose mass and hence
Obesity.

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Case study
A 40-year-old, obese woman presents with
acute pain in the right upper quadrant of her
abdomen as well as vomiting. She is
diagnosed with gall stones and is placed on
ursodeoxycholate, a bile salt used to inhibit
the formation of cholesterol gall stones by
facilitating dissolution of cholesterol.
Which of the following is also a bile
salt ?
A) HMG Co A
B) Mevalonate
C) Lanosterol
D) Squalene
E) Glycocholate

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E) The right answer is Glycocholate. Bile salts and
phospholipids keep cholesterol in the soluble form.
Any condition that causes less bile salt or more
cholesterol formation leads to precipitation of
cholesterol . Initially crystals are formed which upon
accumulation from stones. Synthetically prepared
bile salt, ursodeoxy cholic acid is given for
dissolution of cholesterol stones to those patients
who do not want surgery or are not fit for surgery.
Cholecystectomy is the ultimate cure for
symptomatic gall stones. In majority of cases gall
stones do not cause symptoms.

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Case study
A 65 year-old man with a long history of
diabetes presents to his physician after failing
the driver's license renewal eye examination.
Patients with diabetes have abnormally high
blood glucose levels. Glucose can enter the
lens of the eye, where it can be converted to
Sorbitol. Which of the followings
converts glucose to Sorbitol ?
A) Hexokinase
B) Aldose reductase
C) Sorbitol dehydrogenase
D) Aldose oxidase
E) Glucokinase

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B) Aldose reductase is the right answer. Hexokinase
and Glucokinase are enzymes for phosphorylation of
glucose in the pathway of glycolysis and sorbitol
dehydrogenase is an enzyme to convert sorbitol to
fructose. It is absent in most of the tissues except for
liver, seminal epithelium and testicular tissue.
Aldose oxidase has no role to play. Had Sorbitol
dehydrogenase been there in all tissues, diabetes
related complications would not have occurred,
though this is not the only mechanism responsible
for causing complications but a major contributor.
Aldose reductase is the enzyme responsible
for conversion of glucose to Sorbitol.

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Case Study

A 38-year- old woman sees an advertisement for
a new weight loss medication. The ad claims that
the drug causes your body to burn calories
without having to exercise. In theory which of
the following compounds could make this claim?
A) Rotenone
B) Antimycin
C) Dinitrophenol
D) Amytal
E) Atractyloside

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C)The right answer is Dinitrophenol. The
mechanism of action of the drug is through
uncoupling of oxidative phosphorylation and
Dinitrophenol is the only uncoupler in the list,
rest all inhibitors of ETC except, Atractyloside
which is an inhibitor of ATP/ADP transporter.

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Case study

A known alcoholic is found lying semiconscious at the bottom
of a stairwell with a broken arm by his land lady, who called
an ambulance to take him to the emergency room. Initial
laboratory studies showed are relatively large anion gap of 34
(normal = 9 to 15). His blood alcohol was elevated at 245
mg/dL (intoxication level = 150 to 300 mg/dL), and his blood
glucose was 38 mg/dL (low normal). The patient/s large
anion gap and hypoglycemia can best be explained by
which of the following?
A) Decreased secretion of glucagon
B) Increased secretion of insulin
C) Increased urination resulting from the diuretic effect of
alcohol
D) Inhibition of dehydrogenase enzymes by NADH
E) Inhibition of glycogenolysis by ethanol

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D. Alcoholics frequently do not eat while binge drinking,
so it is most likely that his liver glycogen stores became
depleted and could not increase his blood glucose levels.
The metabolic stress leads to the increase in secretion of
epinephrine and other hormones that mobilize fatty
acids from stored triglycerides in adipose cells. These
fatty acids undergo β-oxidation in the liver but are
converted to ketone bodies because of the inhibition of
the TCA cycle by high levels of NADH produced by the
oxidation of ethanol first to acetaldehyde and acetate.
Key gluconeogenic dehydrogenases are also inhibited by
the elevated levels of NADH, including lactate
dehydrogenase, glycerol 3-phosphate dehydrogenase,
and malate dehydrogenase.

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