Biochemistry Flashcards
What are the essential amino acids? (9)
Histidine, Isoleucine, Leucine,
Methionine, Phenylalanine,
Threonine, Tryptophan,
Valine, Lysine
What are the conditionally non-essential amino acids? (7)
Arginine, Asparagine,
Glutamine, Glycine, Proline,
Serine, Tyrosine
What are the non-essential amino acids?
Alanine, Aspartate,
Cysteine, Glutamate
His
Histidine
Ile
Isoleucine
Leu
Leucine
Lys
Lysine
Met
Methionine
Phe
Phenylalanine
Thr
Threonine
Tro
Tryptophan
Val
Valine
Ala
Alanine
Arg
Arginine
Asn
Asparagine
Asx
Aspartic acid
Glu
Glutamic acid/glutamate
Gln
Glutamine
Gly
Glycine
Pro
Proline
Ser
Serine
Cys
Cysteine
Tyr
Tyrosine
In the biosynthesis of glucose from pyruvate by the liver, the first intermediate formed from pyruvate is
Oxaloacetate
A Mediterranean patient presents to your clinic, looking very pale and complaining of extreme fatigue. He was recently started on a pharmaceutical agent that is known to cause oxidative stress. You sample the patient’s blood and do a blood smear. In the blood smear, the erythrocytes have intracellular inclusions, and some are deformed. What enzyme is missing in this patient?
Glucose-6-phosphate dehydrogenase
T/F: Insulin induces decreased intracellular cyclic AMP
True
T/F: Insulin induces dephosphorylation (activation) of glycogen synthase A
True
T/F: Insulin induces decreased intracellular glucose-6-phosphate
False
T/F: Insulin induces dephosphorylation (inactivation) of glycogen phosphorylase
True
T/F: Insulin induces decreased phosphokinase A (PKA) activity
True
An increase in the activity of which of the following enzymes is most likely to increase the rate of metabolism of glucose-6-phosphate through glycolysis in the liver?
6-phosphofructose-1-kinase
The irreversibility of the pyruvate kinase reaction render hepatic glucogneogenesis dependent on which of the following two ATP or GTP requiring enzymes?
Pyruvate carboxylase and phosphoenolpyruvate carboxykinase
Two infants with separate deficiencies in fructose metabolism—one with deficiency of fructokinase, and the second with aldolase B deficiency—have very different prognoses. Which is worse and why?
Aldolase B deficiency due to sequestration of phosphate
The increase in the intracellular concentration of AMP in muscle after 15 minutes of strenouous exercise has which of the following effects?
Increased breakdown of glycogen
Fructose-2,6-bisphosphate regulates which step in the diagram?
C
After consumption of a carbohydrate-rich meal, the liver continues to convert glucose to glucose-6-phosphate. The liver’s ability to continue this processing of high levels of glucose is important in minimizing increases in blood glucose after eating. What is the best explanation for the liver’s ability to continue this conversion after eating a carbohydrate-rich meal?
The high Km of glucokinase.
T/F: Ionophore uncouplers (thermogenin, dinitrophenol, etc.) work by leaking protons into the intermembrane space
False
T/F: Oligomycin directly poisons the ATPase responsible for generating ATP from the proton gradient
True
T/F: Cyanide and carbon monoxide cause cell death by inducing the mitochondrial apoptosis mechanisms
False
T/F: Mitochondrial DNA mutations that cause lactic acidosis typically affect enzymes involved in the TCA cycle
False
T/F: FADH2 entering the electron transport chain yields 3 ATP, whereas NADH yields only 2 ATP
False
Galactosemia is a genetic error of metabolism associated with
A deficiency of UDP-glucose: galactose-1-phosphate uridylyltransferase
Which is the pathway taken by a bolus of glucose to reach its final home in a CNS neuron?
GI lumen
SGLT1
Enterocyte
GLUT2
Blood
GLUT1
Brain
Glucose is transported into human cells by two different families of membrane-associated carrier proteins: the glucose transporter facilitators (GLUT) and the sodium-coupled glucose transporters (SGLT). If a patient has a defect in the non-sodium-coupled glucose transporters, which cell line is still able to acquire glucose?
Enterocyte
The human body utilizes
D-sugars and L-amino acids
The Hexose Monophosphate Shuttle is required for the production of
Ribose, reduced glutathione, and testosterone
The electrochemical gradient established in the mitochondria is responsible for what two processes?
Production and export of ATP
For the health of your and your family’s colons, you should eat a feast rich in:
Cellulobiose
An alcoholic presents at your clinic with ataxia, confusion, and opthalmoplegia indicating encephalopathy. Blood tests reveal elevated levels of lactate and pyruvate. Based on your knowledge of biochemistry, which of his vitamin deficiencies is producing these symptoms and which associated enzymes or processes are inhibited?
Thiamin deficiency- Pyruvate oxidase particle
Pyruvate is converted to (3):
Alanine, lactate, and acetyl-CoA
What directly inhibits the F0/F1 ATPase?
Oligomycin
What two chemicals directly inhibit electron transport complexes?
Carbon monoxide and cyanide
Present in brown fat and generates heat by dissipating the proton gradient
Thermogenin (UCP1)
General class of compounds that uncouples by dissipating the proton gradient
Ionophore
An over-the-counter drug that acts as an uncoupler when taken in excess
Aspirin
Phosphofructokinase-1 is the rate-limiting enzyme in which pathway
Glycolysis
The rate-limiting step of glycolysis is regulated by
Inhibited by ATP and citrate, stimulated by fructose-2,6-bisphosphate
Glycogen synthase is the rate-limiting enzyme of what pathway?
Glycogen formation
The rate-limiting step of glycogen synthesis is upregulated by
Glucose-6-phosphate and insulin
Glucose-6-phosphate dehydrogenase is the rate-limiting enzyme of what pathway?
Pentose phosphate pathway
Glycogen phosphorylase is the rate-limiting enzyme of what pathway?
Glycogen breakdown
The rate-limiting step of glycogen breakdown is upregulated by what?
Glucagon and epinephrine
A hyperactive 6-year-old girl develops microcytic anemia, cerebral edema, and ataxia.
Determination of which of the following serum enzyme activities is most likely to confirm the
diagnosis?
5-aminolevulininc acid (ALA) dehydrogenase
A 10-year-old boy with light blond hair, pale skin, and significant mental retardation (IQ 50) is most
likely to have a defect at which of the following points in the biochemical pathway?
A
A 17-year-old boy is brought to the emergency department because of severe cramps in his calf
muscles that began after he ran a 1-mile race. His urine is burgundy color. Physical examination
shows tender calf muscles. Laboratory studies show an increased serum creatine kinase activity and
myoglobinuria. Following exercise of his ischemic left forearm, his serum lactic acid concentration
does not increase in blood obtained from the vein proximal to the exercised extremity. This patient
most likely has a deficiency of which of the following enzyme in his muscle?
Glycogen phosphorylase
During conversion of proinsulin to insulin, bonds between which of the following amino acid
residues keep the two chains of the insulin molecule together?
Cysteine
A new born with phenylketonuria is started on a strict phenylalanine-restricted diet. Which of the
following amino acids must be supplemented to avoid negative nitrogen balance?
Tyrosine
A 9-month-old boy is brought to the emergency department after his mother is unable to rouse him.
His past medical history is significant for the onset of seizures at the age of 4 months and for a delay
in reaching developmental milestones. On examination, the patient is found to have poor muscle
tone and an enlarged liver. Laboratory studies show a blood urea nitrogen level of 3.2mg/dL, a
creatinine level of 0.4 mg/dL, and a serum ammonia level of 300 mg/dL. A plasma amino acid
analysis fails to detect citrulline, while his urinary orotic acid level is increased. This patient suffers
from a deficiency of which of the following enzymes?
Ornithine transcarbamoylase
A healthy 30-year-old man is participating in a study of the effects of a competitive inhibitor of
endothelial nitric oxide synthase. After intravenous injection of the inhibitor, blood pressure
immediately increases. Supplementation with which of the following amino acids is most appropriate
to reverse this increase.
Arginine
The destruction of H2O2, which is a mildly toxic reduced oxygen species, is catalyzed by which of
the following enzymes?
Catalase
Uncooked cornstarch is given to patients with certain GSDs before bed for what reason?
Uncooked cornstarch functions like glycogen in that it takes hours to breakdown, thereby
maintaining blood glucose levels (to avoid hypoglycemia and ketosis.)
Patients with Glycogen Storage Diseases typically develop hyperuricemia for which two reasons?
Increased nucleotide breakdown due to hypoglycemia and excess lactate and/or ketones
inhibiting uric acid excretion
No. That is not apple juice… Choose the correct pairing of pathognomonic urine phenotype with
the associated enzyme defect. Sometimes the diagnosis is in the cup.
Black/Dark brown urine = defect in homogentisate oxidase
It is your first night covering the ED and a patient presents with seizures. To decide what drug to
prescribe, you remember back to your neurotransmitter production pathways, learned all those years
ago in HST. What drug will you prescribe and what protein does it inhibit?
Drug: Sodium Valproate. Inhibits: SSAD Dehydrogenase
You are working in Africa with Doctor’s Without Borders. A 10 year old girl, born of a
consanguineous marriage, presents at your clinic with skin eruptions, diarrhea, cerebellar ataxia, and
gross aminoaciduria. Which amino acid will you find in excess in her urine and which molecule is she
deficient in?
Excess Tryptophan with a deficiency of Niacin
Follow the nitrogen. The story of amino acid breakdown is complex. The body must remove
amino groups safely, without increasing ammonia levels. When a peripheral cell breaks down an
amino acid, which pathway will the amino group follow en route to the toilet?
Amino acid -> Transamination -> Glutamate -> Glutamine -> peripheral circulation ->
Liver -> Glutamine deamination -> Nh3 -> urea -> peripheral circulation -> kidney ->
urine -> toilet
An inpatient presents with disorientation, hallucinations, a dry burning mouth and hyperthermia.
Based on the patient’s medical history, you conclude that she has overdosed on Scopolamine.
Scopolamine competitively inhibits cholinergic signaling at muscarinic receptors, and when
administered in excess, results in amplified anti-cholinergic symptoms, as experienced by your patient.
Based on your knowledge of inhibitors and enzyme kinetics, which drug and mechanism is best for
treating the overdose?
Antidote: Physostigmine,
Mechanism: Reversible acetylcholinesterase inhibitor blocks acetylcholine breakdown
A baby born yesterday presents with failure to thrive. She is inactive, has difficulty feeding, and is
displaying signs of CNS dysfunction. Her urine also has an oddly sweet aroma. Which amino acid(s)
need to be limited in her diet to prevent brain damage and possible death?
Leucine, isoleucine, and valine
An older woman presents to your clinic with a history of arthritis and valvulopathies. You also
notice some brown discoloration to her ears and sclera. The patient remembers that she has an
inherited disorder in amino acid metabolism but cannot remember its name. Can you help remind her
of her metabolic diagnosis?
Alkaptonuria
Alpha Methyldopa is an adrenergic antagonist used to treat hypertension. Methyldopa lowers
blood pressure through two mechanisms. Centrally, it acts as a false neurotransmitter and binds
presynaptic alpha2-adrenergic receptors to inhibit sympathetic output. It also competitively inhibits
DOPA decarboxylase. In the presence of Methyldopa, which neurotransmitters do you expect to be
reduced, due to its inhibitory action on DOPA decarboxylase?
Dopamine, norepinephrine, and epinephrine
Barbituates, like several other pharmacologic agents, are contraindicated in patients with
intermittent porphyrias. What is the most likely reason for this contraindication?
Barbituates stimulate porphyrin synthesis, producing accumulation of toxic intermediates
and exacerbation of symptoms
What is the rate-determining enzyme of the Urea Cycle?
Carbamoyl Phosphate Synthase 1
This reflects the carb and amino acid state of the organism
N-acetyl glutamate
Defects in this protein cause the most common urea cycle defect
Ornithine Transcarbamoylase
Defects in this protein cause HHH disorder
Ornithine Transporter (ORTN1)
Defects in this protein are inherited in an X-linked fashion
Ornithine Transcarbamoylase
Requires N-acetyl Glutamate
Carbamoyl Phosphate Synthase 1
Defects in this protein are associated with elevated citrulline and
argininosuccinate
Arginosuccinase
A different form of this enzyme is required in nucleotide synthesis but does not
require N-acetyl glutamate
Carbamoyl Phosphate Synthase 1
Insulin stimulates lipogenesis by
Increasing levels of dephosphorylated pyruvate dehydrogenase
AND
Increasing glucose transport into adipose cells
During fasting, Ketogenesis provides an alternative energy source for tissues.
It is the predominant energy source during long fasts. However, when does
Ketogenesis first begin?
After 1-2 days of fasting
Statins are widely used cholesterol-lowering drugs. They inhibit HMG-CoA Reductase, causing the liver to sense low cholesterol due to decreased production. This results in increased LD receptor trafficking to the surface of hepatocytes, and increased uptake of VLDL, IDL, and LDL. This decreases circulating LDL, and lowers a patient’s LDL cholesterol level. Based on statin’s type of inhibition, what effect would you expect a statin to have on HMG-CoA reductase (in terms of Michaelis-Menten)?
Km to increase and Vmax to remain unchanged
Which two lysosomal storage disorders are associated with a cherry-red spot on the macula, have a high carrier rate among Ashkenazi Jews, and patients die as toddlers?
Niemann-Pick and Tay-Sachs
A patient, who is an Ashkenazi Jew, presents due to chronic fatigue, joint pain, and bruising. Upon exam, you note splenomegaly and hepatomegaly. Blood tests reveal anemia and thrombocytopenia. You decide to do a biopsy of his spleen to better understand disease etiology, and it reveals cells with “crinkled paper” cytoplasms. This patient’s condition would be best treated with:
Enzyme replacement therapy
A 30yo man presents to your clinic with severe limb pain, which developed recently. He believes it is related to the stress of his new job and baby. His chest has also developed a number of raised, purple lesions (angiokeratomas).
Recently, he has been unusually thirty and is urinating excessively. He remembers one great uncle and a cousin, also male, have a similar condition. His great uncle died in his 50’s from heart failure, after having gone blind from a
stroke. His cousin is doing well after receiving enzyme replacement therapy. Which enzyme is deficient in this patient and which intermediate is accumulating?
Enzyme: alpha-galactosidase A
Accumulation product: Ceramide Trihexoside
On Thanksgiving, you likely ate a lot of delicious food some carbohydrate, others protein, and dollop of lipids. Which of the traditional foods (turkey, gravy, crandberry sauce, stuffing, green beans) foods was most calorically dense/capable of generating the highest ATP yield per molecule?
Gravy
After your thanksgiving feast, your rear end’s adipocytes need to store some of your dietary bounty. Using which steps, in which order, will your adipocytes convert acetyl-coA into fatty acids?
Bond formation, Reduction, Dehydration, Reduction
As your new year’s resolution, you decide to get back on the horse and lose the extra pounds acquired over the holidays. In order for your fatty ass-ids to be broken down, beta-oxidation must occur in 3 phases. During the beta oxidation saturation phase, which steps, in which order, must occur?
Dehydration/oxidation, Hydration, Dehydration/oxidation, Thiolysis
You are a resident in the ED and you have a rotating medical student, from the new (new new) pathway. A patient with type 1 diabetes presents with diabetic ketoacidosis. You administer insulin immediately and the patient begins to recover. Shortly thereafter, the medical student takes a urine dipstick and the result shows that ketone levels have increased. The student is shocked at the result and asks you, “Why aren’t her ketones dropping since the patient is improving?” You explain:
During the early recovery phase, blood and urine beta hydroxybutyrate levels drop, while acetoacetate levels rise. The urine dipstick only shows the rise in acetoacetate
What shuttle is required for fatty acid biosynthesis, in addition to playing a role in carbohydrate metabolism?
The citrate shuttle
What is the rate-determining enzyme of fatty acid (FA) synthesis?
Acetyl-CoA Carboxylase
Ketone favored when there is high NADH
Beta-hydroxybutyrate
Location of fatty acid synthesis
Cytosol
Predominant end product of FA breakdown
Acetyl-CoA
Starting molecule for ketone synthesis
Acetyl-CoA
Starting molecule for FA synthesis
Acetyl-CoA
On section, diseased cells have an enlarged cytoplasm that looks like crinkled paper
Gaucher’s disease
Location of last step of urea cycle
Cytosol
Three Phases of Fatty Acid Beta-oxidation
Phase 1: C. Activation
Phase 2: E. Carnitine Shuttle
Phase 3: D. Beta-oxidation desaturation
Three phases of Fatty Acid Formation
Phase 1: A. Citrate Shuttle
Phase 2: F. Fatty acid synthesis
Phase 3: B. Microsomal Elongation and Desaturation
