BIOCHEMISTRY

ANSWERS
1. Answer D:
Hydrophobic amino acids are those with side chains that do not like
to reside in an aqueous environment. For this reason, these amino acids are
more often found buried within the hydrophobic core of a protein, or within the
lipid portion of a membrane.
2. Answer C:
Histidine contains an imidazole ring as its R group. The nitrogen in this ring
possesses a pKa around 6.0, thus it is able to accept or donate a proton at
physiological pH. This fact makes the amino acid an ideal buffering component of a
containing several histidine residues.
3. Answer B:
Hepatic aldolase B is responsible for the hydrolysis of fructose-1- phosphate into
dihydroxyacetone phosphate and glyceraldehyde. The fructose-1- phosphate is
derived via the action of ketohexokinase (fructokinase) and thus if aldolase B is
deficient downstream utilization of fructose will be impaired.
4. Answer E:
The Bohr effect is the physiological phenomenon, first described by Christian
Bohr, describing that the affinity of hemoglobin for oxygen is inversely related both
to acidity and to the concentration of CO2. A decrease in blood pH or an increase in
blood CO2 concentration will result in hemoglobin proteins releasing their
oxygen and a decrease in carbon dioxide or increase in pH will result in hemoglobin
picking up more oxygen. Since carbon dioxide reacts with water to form carbonic
acid, an increase in CO2 results in a decrease in blood pH.
5. Answer C:
Both hemoglobin and myoglobin structure are determined by the high degree of α-
helices present in these proteins. Indeed, most of the amino acids in hemoglobin
form α-helixes, connected by short nonhelical segments.
6. Answer C:
The aquaporin proteins are made up of 6 transmembrane α-helices arranged in a
right-handed bundle. The a-type channels are homo- or heterooligomeric structures
that in the latter case consist of several different proteins. The a-type class of
channel protein has between 2 and 22 transmembrane α-helical domains, thus the
derivation of the name of this type of channel.
7. Answer D:
Symporters are so called because they transport 2 different molecules, or solutes,
across a membrane in the same direction.
8. Answer B:

Facilitated diffusion is the spontaneous passage of molecules or ions across a

biological membrane passing through specific integral transmembrane proteins.
The glucose transporters, of which GLUT4 is a member, carry out sugar transport
via the mechanism of facilitated diffusion.
9. Answer E:

SGLT1 is a sodium-dependent cotransport protein that uses the sodium

electrochemical gradient to actively move glucose into the cell.
10 Answer B:
When acetylcholine binds to acetylcholine receptors on skeletal muscle fibers, it
opens ligand-gated sodium channels in the cell membrane. Sodium ions then enter
the muscle cell, initiating a sequence of steps that finally produce muscle contraction.
11. Answer A:
The earliest symptoms of vitamin A deficiency are night blindness. Additional early
symptoms include follicular hyperkeratosis, increased susceptibility to infection and
cancer, and anemia equivalent to iron deficiency anemia. Prolonged lack of vitamin
A leads to deterioration of the eye tissue through progressive keratinization of the
cornea, a condition known as xerophthalmia.
12. Answer C:
The function of THF (synthesized from folic acid) derivatives is to carry and transfer
various forms of one-carbon units during biosynthetic reactions. The one-carbon
units are methyl, methylene, methenyl, formyl, or formimino groups.
13. Answer E:

Wernicke encephalopathy results from a dietary deficiency in thiamin. The disorder is

most commonly found in chronic alcoholics due to their poor dietetic lifestyles.
Wernicke encephalopathy is a syndrome characterized by ataxia, ophthalmoplegia,
nystagmus, confusion, and impairment of short-term memory.
14. Answer C:

The active form of vitamin C is ascorbic acid itself. The main function of ascorbate is
as a reducing agent in a number of different reactions. Ascorbate is the cofactor for
Cu+-dependent monooxygenases and Fe2+-dependent dioxygenases. Ascorbate has
the potential to reduce cytochromes a and c of the respiratory chain as well as
molecular oxygen. The most important reaction requiring ascorbate as a cofactor is
the hydroxylation of proline residues in collagen. Vitamin C is, therefore, required for
the maintenance of normal connective tissue as well as for wound healing since
synthesis of connective tissue is the first event in wound tissue remodeling.
15. Answer E:

The main symptom of vitamin D deficiency in children is rickets and in adults is

osteomalacia. Rickets is characterized by improper mineralization during the
development of the bones resulting in soft bones. Osteomalacia is characterized by
demineralization of previously formed bone leading to increased softness and
susceptibility to fracture.
16. Answer D:

Numerous amino transferases, such as AST, utilize pyridoxal phosphate (PLP) as a

cofactor. PLP is derived from vitamin B6.
17. Answer C:
Flavin adenine dinucleotide is a derivative of the vitamin riboflavin
18. Answer E:

The pentose phosphate pathway (PPP) is a critical pathway of glucose oxidation within
erythrocytes due to it being required for the generation of NADPH. The transketolase
enzyme, involved in the nonoxidative reactions of the PPP, requires TPP as a cofactor.
19. Answer E:
Thiamin serves as the precursor for TPP. TPP is necessary as a cofactor for the
pyruvate dehydrogenase complex (PDHc) and, therefore, a deficiency thiamin results
in impaired oxidation of pyruvate. This will lead to increased plasma concentrations
of pyruvate. When lactate from erythrocyte and skeletal muscle metabolism reaches
the liver, it will not be readily converted to pyruvate due to the reduced pyruvate
oxidative capacity leading to elevated plasma lactate. In addition, the excess
pyruvate will be a substrate for lactate dehydrogenase, resulting in additionally
increased levels of pyruvate.
20. Answer C:
The most important reaction requiring ascorbate (vitamin C) as a is the hydroxylation
of proline residues in collagen. Deficiency in vitamin C leads to the disease scurvy.
Scurvy is characterized by easily bruised skin, muscle fatigue, soft swollen gums,
decreased wound healing, hemorrhaging, and osteoporosis.
21. Answer E:

Kinases are any of the various enzymes that catalyze the transfer of a phosphate
group from a donor, such as ADP or ATP, to an acceptor. As such, kinases represent a
subfamily of the transferase class of enzyme
22. Answer E:
The phosphate donors during glycolysis are 1,3-bisphosphoglycerate and
phosphoenolpyruvate. These high-energy intermediates of glycolysis function the
same regardless of the cell in which glycolysis is occurring.
23. Answer C:
Essential fructosuria is a benign metabolic disorder caused by the lack of fructokinase
which is normally present in the liver, pancreatic islets, and kidney cortex. The
fructosuria of this disease depends on the time and amount of fructose and sucrose
intake. Since the disorder is asymptomatic and harmless, it may go undiagnosed.
24. Answer D:
Unlike allosteric enzymes that function at some level in the absence on an allosteric
effector, pyruvate carboxylase (PC) has no activity in the absence of acetyl-CoA. This
property defines acetyl-CoA as an obligate activator of PC.
25. Answer E:

The Cori cycle represents a link between metabolic processes that occur in skeletal
muscle and erythrocytes with those occurring in the liver. During anaerobic glycolysis
in muscle the pyruvate is reduced to lactate. This pathway functions exclusively
within erythrocytes because they lack mitochondria necessary for oxidation of NADH
to NAD+. The lactate leaves these tissues, enters the blood, and is transported to the
liver. Within the liver the lactate is oxidized to pyruvate and the pyruvate then serves
as a substrate for glucose synthesis. The glucose leaves the liver and can be used by
muscle and erythrocytes again.
26. Answer C:
The inner mitochondrial membrane is impermeable to oxaloacetate (OAA). In order
for the carbon atoms of OAA to be transported out into the cytosol, where they can
serve as precursors for glucose synthesis, OAA is reduced to malate. The malate is
transported across the inner mitochondrial membrane where in the cytosol is
oxidized to OAA.
27. Answer C:

In the absence of adequate carbohydrate the body will begin to divert stored fats
into the metabolic pool in order to allow for adequate energy production. In
addition, the liver will oxidize fatty acids to acetyl-CoA and then the acetyl-CoA into
ketone synthesis to ensure the brain receives adequate amounts of an oxidizable
energy source. When adipose tissue is stimulated to release fatty acids stored in
triglycerides, the glycerol backbone diffuses into the blood and is delivered to the
liver. Within the liver, glycerol is phosphorylated and converted to DHAP and then
diverted into the glucose production via gluconeogenesis.
28. Answer D:
The activity of glycogen synthase is inhibited when the enzyme undergoes
phosphorylation. There are a number of kinases that target this enzyme for
inhibition including glycogen synthase-phosphorylase kinase, PKA, PKC, and GSK- 3.
Thus, removal of the phosphate added by any of these enzymes would result in
increased glycogen synthase activity.
29. Answer B:
Increased intracellular cAMP results in the activation of PKA. PKA phosphorylates
and activates glycogen synthase-phosphorylase kinase, which will phosphorylate
and activate phosphorylase while also phosphorylating and inhibiting glycogen
synthase. The increased activity of phosphorylase results in increased release of
glucose from glycogen and its subsequent release to the blood.
30. Answer E:
Glycogen synthase is the enzyme responsible for the incorporation of glucose into
glycogen. The active form of glucose used as a substrate by glycogen synthase is
UDP glucose
31. Answer A:

During periods of fasting, the pancreas releases glucagon to stimulate the liver to
deliver glucose to the blood. When glucagon binds to its receptors on hepatocytes,
there is activation of adenylate cyclase resulting in increased cAMP with consequent
activation of PKA. PKA phosphorylates and activates glycogen synthase-
phosphorylase kinase, which will phosphorylate and activate phosphorylase while
also phosphorylating and inhibiting glycogen synthase. The increased activity of
phosphorylase results in increased release of glucose from glycogen while the
inhibited glycogen synthase reduces glycogenesis.
32. Answer E:
Transketolase functions to transfer 2-carbon groups from substrates of the PPP, thus
rearranging the carbon atoms that enter this pathway. Like other enzymes that
transfer 2-carbon groups, transketolase requires TPP as a cofactor in transfer
reaction.
33. Answer E:

The reactions of fatty acid biosynthesis and steroid biosynthesis large amounts of
NADPH. As a consequence, cells of the liver, adipose tissue, adrenal cortex, testis,
and lactating mammary gland have high levels of the PPP enzymes. Skeletal muscle,
although active at de novo fatty acid synthesis, have the lowest levels of expression
of enzymes of the PPP.
34. Answer B:
The key regulated enzyme of the PPP, G6PDH, catalyzes the initial oxidation
reaction of the pathway.
35. Answer D:
The conversion of succinate to fumarate is catalyzed by the enzyme succinate
dehydrogenase. This enzyme requires FAD, derived from riboflavin, as a cofactor
for the reaction.
36. Answer D:
Succinyl-CoA synthetase catalyzes the conversion of succinyl-CoA to succinate.
Simultaneously, the reaction generates GTP from GDP, utilizing the high-energy bond
between CoA and succinate. This formation of GTP is referred to substrate-level
phosphorylation to distinguish it from ATP production during oxidative
phosphorylation.
37. Answer D:

The reduced electron carriers generated via reactions of the TCA cycle (NADH and
FADH2) are subsequently reoxidized to NAD+ and FAD via the oxidative
phosphorylation pathway.
38. Answer C:
Reduced CoQ (CoQH2) diffuses in the lipid phase of the membrane and donates its
electrons to complex III, whose principal components are the heme proteins
cytochromes b and a non-heme protein, known as the Rieske iron-sulfur protein.
39. Answer A:

Cyanides bind to the heme iron in cytochrome a+a3 of complex IV. This same
cytochrome is the site of carbon-monoxide binding.
40. Answer D:

All biological reactions which involve electron flow are considered oxidation-
reduction reactions. The basic definition can be defined as one reactant becomes
oxidized (loses electrons) while another becomes reduced (gains electrons).
41. Answer E:
Chronic ethanol consumption and alcohol metabolism contributes to the spectrum
of metabolic disorders frequently found in alcoholics. These disorders include fatty
liver syndromes such as NAFLD and NASH, hyperlipidemia, lactic acidosis,
ketoacidosis, and hyperuricemia. The first stage of liver damage following chronic
alcohol consumption is the appearance of fatty liver, which is followed by
inflammation, apoptosis, fibrosis, and finally cirrhosis. These negative and toxic
changes within the liver are irreversible even when alcohol consumption is.
42. Answer D:

Metabolism of ethanol occurs within the liver and involves oxidation to

acetaldehyde and then to acetate catalyzed by ADH and ALDH, respectively
43. Answer E:
Both isoforms of ACC are allosterically activated by citrate and inhibited by
palmitoyl-CoA and other short- and long-chain fatty acyl-CoAs. Citrate triggers the
polymerization of ACC1 which leads to significant increases in its activity. Although
ACC2 does not undergo significant polymerization (presumably due to its
mitochondrial association), it is allosterically activated by citrate. and other
dicarboxylic acids can also allosterically activate both ACC isoforms.
44. Answer A:
The major building block for the synthesis of TGs, in tissues other than adipose
tissue, is glycerol. The glycerol backbone of TG is activated by phosphorylation at the
sn3 position by glycerol kinase.
45. Answer C:
Platelet-activating factor (PAF) is a unique complex lipid of the plasmalogen family.
PAF functions in hypersensitivity, acute inflammatory reactions, and anaphylactic
shock by increased vasopermeability, vasodilation, and bronchoconstriction. Excess
production of PAF production may be involved in the morbidity associated with
toxic shock syndrome and strokes.
46. Answer C:
Adipocytes lack glycerol kinase; therefore, dihydroxyacetone phosphate (DHAP),
produced during glycolysis, is the precursor for triglyceride synthesis in adipose
tissue. The utilization of DHAP for the backbone is carried out through either of 2
pathways depending on whether the synthesis of triglycerides is carried out in the
mitochondria and ER or the ER and the peroxisomes. In the former case, the action
of glycerol-3-phosphate dehydrogenase converts DHAP to glycerol 3-phosphate.
47. Answer D:

Arachidonic acid is found esterified to the sn2 position of the glycerol backbone of
membrane phospholipids. Activation of membrane receptors, such as that which is
activated by PAF, leads to activation of phospholipase A2, which hydrolyzes the
ester bond at the sn2 position in phospholipids
48. Answer B:
Oxidation of fatty acids occurs in the mitochondria and the peroxisomes via similar
enzymatic pathways referred to as β-oxidation. Fatty acids of between 4 and 8 and
between 6 and 12 carbon atoms in length, referred to as short- and medium-chain
fatty acids (SCFAs and MCFAs), respectively, are oxidized exclusively in the
mitochondria. Long-chain fatty acids (LCFAs: 10-16 carbons long) are oxidized in
both the mitochondria and the peroxisomes with the peroxisomes exhibiting
preference for 14-carbon and longer LCFAs. Very-longchain fatty acids (VLCFAs: 17-
26 carbons long) are exclusively oxidized in the peroxisomes.
49. Answer D:
Ketogenesis occurs in the liver from acetyl-CoA during high rates of fatty acid oxidation
and during early starvation. The principal ketone bodies are acetoacetate and β-
hydroxybutyrate, which are reversibly synthesized in a reaction catalyzed by β-
hydroxybutyrate dehydrogenase. The liver delivers β-hydroxybutyrate to the circulation
where it is taken up by nonhepatic tissue for use as an oxidizable fuel. The brain will
derive much of its energy from ketone body oxidation during fasting and starvation.
Within extrahepatic tissues, β-hydroxybutyrate is converted to acetoacetate by β-
hydroxybutyrate dehydrogenase. Acetoacetate is reactivated to acetoacetyl-CoA in a
reaction catalyzed by succinyl-CoA: 3-oxoacid-CoAtransferase (also called succinyl-CoA-
acetoacetate-CoA-transferase or acetoacetate: succinyl-CoA-CoA transferase), which
uses succinyl-CoA as the source of CoA. This enzyme is not present in hepatocytes. The
acetoacetyl-CoA is then converted to 2 moles of acetyl-CoA by the thiolase reaction of
fatty acid oxidation.
50. Answer E:
Ketone bodies are synthesized in the liver from acetyl-CoA. Acetyl- CoA can be
derived from the oxidation of pyruvate, certain amino acids, and fatty acids. By far,
the largest concentration of acetyl-CoA is derived from the β- oxidation of fatty acids
such as palmitic acid.
51. Answer D:
During periods of fasting and starvation the liver diverts acetyl- CoA, derived from the
oxidation of amino acids and fatty acids, into ketogenesis. The ketone bodies,
acetoacetate and β-hydroxybutyrate, produced by the liver are then delivered to the
blood and oxidized by peripheral tissues, such as the brain, for ATP production.
52. Answer A:

During the pathway of fatty acid oxidation the molecules are first activated by
attachment of CoA generating a fatty acyl-CoA derivative. The fatty acyl-CoA
derivatives are then substrates for the enzyme carnitine palmitoyltransferase I,
which substitutes carnitine for CoA generating a fatty acylcarnitine which can then
be transported across the outer mitochondrial membrane
53. Answer E:
When fatty acids are released from adipose tissue stores, they enter the circulation
as free fatty acids (FFAs) and are bound to albumin for transport to peripheral
tissues. When the fatty acid–albumin complexes interact with cell surfaces, the
dissociation of the fatty acid from albumin represents the first step of the cellular
uptake process.
54. Answer A:
Regulation of HMG-CoA reductase (HMGR) is controlled primarily by a short-term
regulatory cascade that results in phosphorylation of the enzyme. Once
phosphorylated, HMGR is much less active and thus, cholesterol biosynthesis will be
reduced. In order to return to a more active state, the phosphorylated sites on HMGR
must be dephosphorylated. All of the enzyme choices listed are involved in of HMGR
activity, however, only AMP-activated kinase (AMPK) activity is affected by alteration
in the ATP:ADP ratio in cells. When ATP levels fall, AMP levels will rise and AMPK
becomes fully activated. Phosphorylation of HMGR by AMPK results in reduced
cholesterol synthesis, which results in reduced ATP consumption
55. Answer B:

HMG-CoA reductase is the rate-limiting enzyme of cholesterol biosynthesis and the

major site for regulation of this metabolic pathway. Regulation of HMGR through
covalent modification occurs as a result of phosphorylation and dephosphorylation.
The enzyme is most active in its unmodified form. Phosphorylation of the enzyme
decreases its activity. HMGR is phosphorylated by AMPK, which itself is activated via
phosphorylation. Increased AMPK activity would, therefore, have a significant
negative impact on the rate of HMGR activity.
56. Answer B:

Nicotinic acid, derived from niacin, reduces the plasma levels of VLDLs and LDLs by
inhibiting hepatic VLDL secretion, as well as suppressing the flux of FFA release from
adipose tissue by inhibiting lipolysis. In addition, nicotinic administration strongly
increases the circulating levels of HDLs. Patient compliance with nicotinic acid
administration is sometimes compromised because of the unpleasant side effect of
flushing (strong cutaneous vasodilation).
57. Answer A:
Regulation of HMG-CoA reductase (HMGR) activity is the primary means for
controlling the level of cholesterol biosynthesis. This enzyme catalyzes the conversion
of mevalonate to hydroxymethyl glutaryl-CoA. HMGR activity is controlled by 4
distinct mechanisms: feedback inhibition, control of gene expression, rate of enzyme
degradation, and phosphorylation-dephosphorylation. The first 3 control mechanisms
are exerted by cholesterol itself. Cholesterol acts as a feedback inhibitor of preexisting
HMGR as well as inducing rapid degradation of the enzyme. In addition, when
cholesterol is in excess, the amount of mRNA for HMGR is reduced because of
decreased expression of the gene.
58. Answer A:

Bile acids are modified, prior to secretion from the liver into the bile canaliculi, by
addition of the amino acid glycine or taurine. The addition of these amino groups
increases amphipathic nature of bile acids making them more easily secretable as
well as less cytotoxic.
59. Answer E:
The cellular uptake of cholesterol from LDL occurs following the interaction of LDL
with the LDL receptor (also called the apoB-100/apoE receptor). Both apoB-100,
which is exclusively associated with LDL, and apoE are required for LDL receptor-
mediated endocytosis of LDL. The importance of apoE in cholesterol uptake by LDL
receptors has been demonstrated in transgenic mice lacking functional apoE genes.
These mice develop severe atherosclerotic lesions at 10 weeks of age. Therefore,
increased levels of apoE would be associated with a higher hepatic uptake of LDL,
leading to reduced levels in the blood.
60. Answer B:
Chylomicrons are assembled in the intestinal mucosa as a means to transport dietary
cholesterol and triglycerides to the rest of the body. The apolipoproteins that
predominate before the chylomicrons enter the circulation include apoB-48, apoA-I,
apoA-II, and apoA-IV, where apoB-48 is exclusively associated with chylomicrons.
61. Answer B:
Chylomicrons are assembled in the intestinal mucosa as a means to transport
dietary cholesterol and triglycerides to the rest of the body. Chylomicrons are,
therefore, the molecules formed to mobilize dietary (exogenous) lipids and would,
therefore, not be produced during periods of starvation or fasting.
62. Answer E:
The liver takes up LDL (and IDL) after they have interacted with the LDL receptor to
form a complex, which is endocytosed by the cell. For LDL receptors in the liver to
recognize LDL, they require the presence of both apoB-100 and apoE (the LDL
receptor is also called the apoB-100/apoE receptor). Lack of functional LDL receptors
is associated with hypercholesterolemia and the increased development of
atherosclerotic plaques, leading to coronary heart disease.
63. Answer B:
Chylomicrons are assembled in the intestinal mucosa as a means to transport dietary
cholesterol and triglycerides to the rest of the body. Chylomicrons are, therefore, the
molecules formed to mobilize dietary (exogenous) lipids. Failure to produce
chylomicrons would, therefore, lead to impaired absorption of dietary lipids.
64. Answer A:
The dietary intake of both fat and carbohydrate, in excess of the needs of the body,
leads to their conversion into triglycerides in the liver. These triglycerides are
packaged into VLDL and released into the circulation for delivery to the various
tissues (primarily muscle and adipose tissue) for storage or production of energy
through oxidation. VLDL are, therefore, the molecules formed to transport
endogenously derived triglycerides to extrahepatic tissues. The fatty acid portion of
VLDL is released to the tissues through the action of lipoprotein lipase, which leads
to increasing density of VLDL to IDL and LDL.
65. Answer A:
Alanine transaminase has an important function in the delivery of skeletal muscle
carbon and nitrogen (in the form of alanine) to the liver. In skeletal muscle, pyruvate
is transaminated to alanine, thus affording an additional route of nitrogen transport
from muscle to liver. In the liver, alanine transaminase transfers ammonia to α-
ketoglutarate and regenerates pyruvate. The pyruvate can then be diverted into
gluconeogenesis. This process is referred to as the glucose-alanine cycle.
66. Answer D:

Glutamine is the major amino acid found in the circulatory system. Its role there is to
carry ammonia to and from various tissues but principally from peripheral tissues to
the kidney, where the amide nitrogen is hydrolyzed by the enzyme glutaminase; this
process regenerates glutamate and free ammonium ion, which is excreted in the
urine.
67. Answer D:
Major reactions that involve the regulation of plasma pH as well as the level of
circulating ammonia involve the hepatic and renal enzymes glutamate dehydrogenase
(GDH), glutamine synthase (GS), and glutaminase. The liver compartmentalizes GS and
glutaminase in order to control the flow of ammonia into glutamine or urea. Under
acidotic conditions the liver diverts ammonia to glutamine via the GS reaction. The
glutamine then enters the circulation. In fact, glutamine is the major amino acid of the
circulation and its role is to ferry ammonia to and from various tissues. In the kidneys,
glutamine is hydrolyzed by glutaminase (yielding glutamate) releasing the ammonia to
the urine. There the ammonia ionizes to ammonium ion, NH4 +, which reduces the
circulating concentration of hydrogen ion resulting in an increase in the pH. Additionally,
the glutamate can be converted to α- ketoglutarate yielding another mole of ammonia,
which is ionized by hydrogen ions further increasing the pH.
68. Answer A:
Seemingly normal full-term infants suffering from urea cycle defects will usually
become lethargic and need stimulation to feed within 24–72 hours after . When
presented in the emergency many will be comatose. One obvious outward clinical
sign will be a bulging fontanel due to the ammonia-induced . If a correct diagnosis of
hyperammonemia is not made in a timely manner these infants will die.
69. Answer A:
Unlike fats and carbohydrates, nitrogen has no designated storage depots in the
body. Since the half-life of many proteins is short (on the order of hours), increased
dietary intake of protein will result in an concomitant increase in amino acid
degradation resulting in increased nitrogen excretion. When more nitrogen is
excreted than is incorporated into the body, an individual is in negative nitrogen
balance. Normal, healthy adults are generally in nitrogen balance, with intake and
excretion being very well matched. Young growing children, adults recovering from
major illness, and pregnant women are often in positive nitrogen balance. Their
intake of nitrogen exceeds their loss as net protein synthesis proceeds.
70. Answer C:
The dominant reactions involved in removing amino acid nitrogen from the body are
known as transaminations. Transaminations involve moving an α- amino group from
a donor α-amino acid to the keto carbon of an acceptor α-keto acid. These reversible
reactions are catalyzed by a group of intracellular enzymes known as
aminotransferases, which generally employ covalently bound pyridoxal as a cofactor.
71. Answer C:

Glutamate plays the central role in mammalian nitrogen flow, serving as both a
nitrogen donor and nitrogen acceptor. Glutamine is the nitrogen repository found in
the circulatory system. Its role there is to carry ammonia to and from various tissues
but principally from peripheral tissues to the kidney. In the , glutamine is hydrolyzed
by glutaminase (yielding glutamate) releasing the ammonia to the urine.
Additionally, the glutamate can be converted to α-ketoglutarate yielding another
mole of ammonia which is excreted.
72. Answer B:

α-Ketoglutarate is capable of accepting 2 moles of ammonia, first via the action of

glutamate dehydrogenase yielding glutamate and then via glutamine synthetase
yielding glutamaine. Glutamate plays the central role in mammalian nitrogen flow,
serving as both a nitrogen donor and nitrogen acceptor. Glutamine is the nitrogen
repository found in the circulatory system. Its role there is to carry ammonia to and
from various tissues but principally from peripheral tissues to the kidney.
73. Answer C:
Major reactions that involve the regulation of plasma pH as well as the level of
circulating ammonia involve the hepatic and renal enzymes glutamate
dehydrogenase (GDH), glutamine synthase (GS), and glutaminase. Under acidotic
conditions the liver diverts ammonia to glutamine via the GS reaction. The
glutamine then enters the circulation. In the kidneys, glutamine is hydrolyzed by
glutaminase yielding glutamate) releasing the ammonia to the urine. There the
ammonia ionizes to ammonium ion, NH4 +, which reduces the circulating
concentration of hydrogen ion resulting in an increase in the pH.
74. Answer C:
Histamine is a preformed inflammatory mediator found principally in mast cells and
basophils that has a major role in the early vascular changes of inflammation, that is,
dilation of precapillary arterioles, which produces the local redness (rubor) and
warmth (calor), and the increased permeability of postcapillary venules, which
produces the swelling (tumor).
75. Answer E:
A deficiency in phenylalanine hydroxylase (PAH) is the cause of PKU. Tyrosine is
produced in cells by hydroxylating the essential amino acid phenylalanine and this
reaction is catalyzed by PAH. Half of the phenylalanine required goes into the
production of tyrosine; if the diet is rich in tyrosine itself, the
requirements for phenylalanine are reduced by about 50%.
76. Answer A:
Glutamine is the major amino acid of the circulation and its role is to ferry ammonia
to and from various tissues. In the kidneys, glutamine is hydrolyzed by glutaminase
(yielding glutamate), releasing the ammonia into the urine. There, the ammonia
ionizes to ammonium ion, NH4 +, which reduces the circulating concentration of
hydrogen ion resulting in an increase in the pH. Additionally, the glutamate can be
converted to α-ketoglutarate yielding another mole of ammonia, which is ionized by
hydrogen ions further increasing the pH.
77. Answer B:

The side chain of cysteine contains a reactive sulfur that can become oxidized,
forming intermolecular disulfide bonds. Exposure of cysteine to air, such as could
be the case in highly oxygen-rich tissue like erythrocytes, can result in oxidation of
the sulfur.
78. Answer A:

Creatine is synthesized in the liver by methylation of guanidoacetate using SAM as

the methyl donor. Guanidoacetate itself is formed in the kidney from the amino
acids arginine and glycine. Creatine is used as a storage form of high energy
phosphate. The phosphate of ATP is transferred to creatine, generating creatine
phosphate, through the action of creatine phosphokinase. The reaction is reversible
such that when energy demand is high (eg, during muscle exertion) creatine
phosphate donates its phosphate to ADP to yield ATP.
79. Answer D:

Epinephrine and norepinephrine are catabolized to inactive compounds through

the sequential actions of catecholamine-O-methyltransferase (COMT) and
monoamine oxidase (MAO). The terminal catabolic product of the actions of these
2 enzymes is vanillylmandelic acid.
80. Answer A:
Tetrahydrofolate (THF) is regenerated from the dihydrofolate (DHF) product of the
thymidylate synthase reaction by the action of dihydrofolate reductase (DHFR). Cells
that are unable to regenerate THF suffer defective DNA synthesis and eventual death.
Many anticancer drugs act directly to inhibit thymidylate synthase, or indirectly, by
inhibiting DHFR. Many DHFR inhibitors have been synthesized, including
methotrexate, aminopterin, and trimethoprim. Each of these is an analog of folic
acid.
81. Answer D:
Synthesis of the purine nucleotides requires 5 moles of ATP, 2 moles of glutamine, 1
mole of glycine, 1 mole of CO2, 1 mole of aspartate, and 2 moles of formate.
82. Answer E:
Both the salvage and de novo synthesis pathways of purine and pyrimidine
biosynthesis lead to production of nucleoside-5′-phosphates through the utilization
of an activated sugar intermediate. The activated sugar used is 5- phosphoribosyl-1-
pyrophosphate (PRPP). PRPP is generated by the action of PRPP synthetase.
83. Answer A:
Synthesis of the pyrimidines requires 1 mole of glutamine, 1 mole of ATP, and 1
mole of CO2 (which form carbamoyl phosphate) and 1 mole of aspartate. An
additional mole of glutamine and ATP are required in the conversion of UTP to
CTP.
84. Answer C:
Lesch-Nyhan syndrome is a disorder related to defects in the activity of the purine
nucleotide salvage enzyme, hypoxanthine-guanine phosphoribosyltransferase
(HGPRT). The characteristic clinical features of the LNS are mental retardation,
spastic cerebral palsy, choreoathetosis, uric acid urinary stones, and self-destructive
biting of fingers and lips. The uric acid overproduction and its associated
consequences (eg, gouty arthritis) are the result of a block in purine nucleotide
salvage, leading to increased catabolism to uric acid.
85. Answer E:
Paroxysmal nocturnal hemoglobinuria is a hemolytic anemia in which an acquired cell
membrane defect increases red blood cell susceptibility to lysis by endogenous
complement. Intravascular hemolysis overwhelms hepatic enzyme conjugation capability
and leads to an increase in unconjugated bilirubin (water-insoluble) in serum. The liver
enzyme glucuronyl transferase converts unconjugated bilirubin into conjugated bilirubin
(now water-soluble), which is then excreted by hepatocytes into the bile. After secretion of
bile into the intestine, ileal and colonic bacteria convert conjugated bilirubin into
urobilinogen. A fraction of urobilinogen is oxidized to stercobilin and directly excreted in
feces (and hence, would not be a urinary metabolite). The remaining urobilinogen is
reabsorbed from the intestine and reenters the portal circulation where a portion is taken
up by the liver and reexcreted into bile, while the rest bypasses the liver and is excreted by
the kidney. Therefore, in hemolytic anemias, increased liver excretion of conjugated
bilirubin will lead to an increase in urinary urobilinogen levels. Note that this is in contrast
to biliary tract obstruction in which failure of conjugated bilirubin to enter intestine would
lead to decreased levels of both fecal and urinary urobilinogen.
86. Answer A:
The most commonly occurring hepatic porphyria is acute intermittent porphyria,
which is caused by a defect in porphobilinogen deaminase
87. Answer D:
The first reaction in heme biosynthesis takes place in the mitochondrion and
involves the condensation of 1 glycine and 1 succinyl-CoA by the pyridoxal
phosphate-containing enzyme, δ-aminolevulinic acid synthase (ALAS).
88. Answer C:
Urobilinogen is a colourless product of bilirubin catabolism formed in the intestines by
bacterial action. It is one of the many bile pigments. Each of the other compounds
represents intermediates in heme synthesis or heme derivatives.
89. Answer B:
In hepatocytes, bilirubin-UDP-glucuronyltransferase (bilirubin- UGT) adds 2
equivalents of glucuronic acid to bilirubin to produce the more watersoluble,
bilirubin diglucuronide derivative. The increased water solubility of the tetrapyrrole
facilitates its excretion with the remainder of the bile as the bile pigments.
90. Answer B:
Lipid is the most concentrated form of energy storage, holding 9.4 kcal/g. For a
typical 70-kg human, over 130,000 kcal is typically stored as fat. Storage of energy as
available protein is about 20,000 kcal while storage as carbohydrate is about 3000
kcal.
91. Answer D:
The binding of DNA by the histones generates a structure called the nucleosome.
The nucleosome core contains an octamer protein structure consisting of 2 subunits
each of H2A, H2B, H3, and H4. Histone H1 occupies the internucleosomal DNA and is
identified as the linker histone. The nucleosome core contains approximately 150 bp
of DNA
92. Answer A:
The anthracyclins were originally isolated from the fungus, Streptomyces.
Doxorubicin (Adriamycin, Doxil, Rubex) and daunorubicin (Cerubidine, DaunoXome,
Daunomycin, Rubidomycin) have similar modes of action, although doxorubicin is the
more potent of the 2 and is used in the treatment of breast cancers, lymphomas, and
sarcomas. The anthracyclins inhibit the actions of topoisomerase II.
93. Answer B:

The promoter region is a specific sequence of DNA upstream of the transcription

start site of a gene. Promoters stimulate the initiation of transcription. Promoters
are located near the genes they transcribe, on the same strand and upstream on
the DNA.
94. Answer D:
The genetic code of an mRNA is contained within the triplet codons which dictate
the amino acids to be incorporated during protein synthesis.
95. Answer D:
In eukaryotes, initiator AUGs are generally, but not always, the first encountered by
the translational machinery. A specific sequence context, surrounding the initiator
AUG, aids ribosomal discrimination and is referred to as the Kozak consensus
sequence.
96. Answer D:

During protein elongation, the peptide attached to the tRNA in the Psite is
transferred to the amino group at the aminoacyl-tRNA in the A-site forming a new
peptide bond. This reaction is catalyzed by peptidyltransferase activity which resides
in what is termed the peptidyltransferase center (PTC) of the large ribosomal
subunit (60S subunit). This enzymatic process is termed transpeptidation. This
enzymatic activity is not mediated by any ribosomal proteins but instead by
ribosomal RNA contained in the 60S subunit. This RNA-encoded enzymatic activity
is referred to as a ribozyme.
97. Answer D:
Initiation of translation in both prokaryotes and eukaryotes requires a specific
initiator tRNA, tRNAi met, that is used to incorporate the initial methionine
residue into all proteins.
98. Answer D:
The genetic code that dictates the sequence of amino acids in a protein is contained
within the codons of the mRNA.
99. Answer E:
Cell migration requires the hydrolysis of the extracellular matrix (ECM) holding the
cells into a tissue or a tumor. The primary enzymes responsible for the degradation
and remodeling of the ECM are the matrix metalloproteinases.
100 Answer E:
Within smooth muscle cells, nitric oxide (NO) reacts with the heme moiety of a
soluble guanylyl cyclase, resulting in activation of the latter and a consequent
conversion of GTP to cGMP. The net effect is the activation of cGMPdependent
protein kinase (PKG) and the phosphorylation of substrates leading to smooth
muscle cell relaxation.
101. Answer B:
In order to accurately determine the identity of any given RNA it is necessary to
determine the nucleotide sequences of the encoding gene or to generate cDNA
clones of the RNAs and compare their nucleotide sequences. Blotting and
hybridization of 2 different RNAs might demonstrate that they are identical in size,
but that is all the information one would be able to use from that analysis.
102. Answer E:

Iron is transported across the basolateral membrane of intestinal enterocytes into

the circulation, through the action of the transport protein ferroportin (also called
IREG1 = iron-regulated gene 1). Associated with ferroportin is the enzyme hephaestin
(a copper-containing ferroxidase with homology to ceruloplasmin) which oxidizes the
ferrous form back to the ferric form. Once in the circulation, ferric form of iron is
bound to transferrin and passes through the portal circulation of the liver.
103. Answer C:
Ferritin is the major protein used for intracellular storage of iron. Ferritin without
bound iron is referred to as apoferritin. Apoferritin is a large polymer of 24
polypeptide subunits. This multimeric structure of apoferritin is able to bind up to
2000 iron atoms in the form of ferric phosphate. The majority of intracellularly
stored iron is found in the liver, skeletal muscle, and reticuloendothelial cells.
104. Answer A:

Cholecystokinin (CCK) is secreted from intestinal enteroendocrine I cells

predominantly in the duodenum and jejunum. Upon binding its receptors in the
gut CCK induces contractions of the gallbladder and release of pancreatic enzymes
and also inhibits gastric emptying.
105. Answer E:

Salivary α-amylase is a major contributor to the digestions of dietary starches.

Indeed, this enzyme is responsible for a significant portion of carbohydrate
digestion in the mouth, esophagus, and stomach.
106. Answer A:
The activity of salivary and pancreatic α-amylase is the hydrolysis of starch at α(1,4)-
glycosidic linkages. Amylase functions at random locations along the starch polymer
hydrolyzing long-chain carbohydrates. The products of amylase activity on amylose
are maltotriose and maltose, and those from amylopectin are maltose, glucose and
limit dextrins.
107. Answer C:
Gastrin is produced in enteroendocrine G cells of the gastric antrum and duodenum
and exists in 2 forms, little gastrin (17 amino acids) and big gastrin (34 amino acids).
Gastrin is responsible for inducing gastric acid production and pepsin secretion.
Both forms of gastrin bind to the CCK2 (CCKB) receptor on stomach and gut parietal
cells with an affinity equal to that of CCK. Activation of the CCKB receptor by gastrin
triggers the production of gastric acid.
108. Answer B:

Ghrelin is produced and secreted by the X/A-like enteroendocrine cells of the

stomach oxyntic (acid-secreting) glands. The major effect of ghrelin is exerted within
the central nervous system at the level of the arcuate nucleus where it stimulates
the release of neuropeptide Y (NPY) and agouti-related protein (AgRP). The actions
of NPY and AgRP enhance appetite and thus, food intake.
109. Answer E:
The orexin peptides function to increase food consumption. However, in addition to
increased feeding behavior central orexin action increases wakefulness and
suppresses REM sleep. These latter observations demonstrate that orexins play a
causative role in the regulation of sleep-wake cycles. Indeed, loss of orexin function
results in a condition in animals that mimics the sleep disorder in humans known as
narcolepsy
110. Answer E:

PYY produced by and secreted from intestinal enteroendocrine L cells of the ileum
and colon. The release of PYY results in reduced gut motility, a delay in gastric
emptying, and an inhibition of gallbladder contraction. All of these actions are
associated with the ileal brake.
111. Answer B:
Ghrelin is produced and secreted by the X/A-like enteroendocrine cells of the
stomach oxyntic (acid-secreting) glands. The major effect of ghrelin is exerted within
the central nervous system at the level of the arcuate nucleus where it stimulates
the release of neuropeptide Y (NPY) and agouti-related protein (AgRP). The actions
of NPY and AgRP enhance appetite and thus, food intake.
112. Answer A:

The major biological actions of adiponectin are increases in insulin sensitivity and
fatty acid oxidation
113. Answer D:
The hallmark feature of the metabolic syndrome is indeed insulin resistance. The
hyperlipidemia typical in obese individuals leads to progressive insulin resistance,
particularly in adipose tissue and skeletal muscle.
114. Answer D:

The primary targets of insulin action, at the level of glucose homeostasis, are
adipose tissue and skeletal muscle. Both of these tissues express GLUT4 which is
stimulated to migrate to the plasma membrane in response to insulin action
resulting in increased glucose disposal from the blood. Since the overall cellular
mass of skeletal muscle is so large, in relation to all other tissues, insulin-mediated
glucose uptake into this tissue represents one of the major glucoselowering
effects of the hormone.