Biochemistry - Metabolism Part 2 Flashcards
Where in the cell is the enzyme glucose-6-phosphatase found?
Endoplasmic reticulum
In which tissues are the enzymes of gluconeogenesis found?
Liver, kidney, and intestinal epithelium
What product of the pentose phosphate pathway (hexose monophosphate shunt) facilitates steroid and fatty acid synthesis?
NADPH
What is the function of NADPH in the erythrocyte?
It reduces glutathione
What are the two phases of the hexose monophosphate shunt (pentose phosphate pathway)?
Irreversible oxidative phase and reversible nonoxidative phase
What key enzyme regulates the oxidative phase of the hexose monophosphate shunt?
Glucose-6-phosphate dehydrogenase
How many adenosine triphosphate molecules are used and produced by the hexose monophosphate shunt (pentose phosphate pathway)?
0
What vitamin is required for the nonoxidative phase of the hexose monophosphate shunt?
The transketolases that catalyze the nonoxidative reactions require thiamine (vitamin B1) as a cofactor
What four products are formed after both phases of the hexose monophosphate shunt?
Ribose-5-phosphate, G3P, F6P, and NADPH are the products
Which product of the hexose monophosphate shunt is used in nucleotide synthesis?
Ribose-5-phosphate
How are G3P and F6P utilized in the cell following the hexose monophosphate shunt?
These are glycolytic intermediates and can enter glycolysis
Name three sites of fatty acid or steroid synthesis that show high pentose phosphate pathway (hexose monophosphate shunt) activity.
Lactating mammary glands, liver, adrenal cortex
Do the reactions of the hexose monophosphate shunt (pentose phosphate pathway) take place in the mitochondria or the cytosol of a cell?
The cytosol
Where would you find elevated activity of the pentose phosphate pathway, but no fatty acid or steroid synthesis?
In the red blood cells; the reducing equivalents formed are necessary to neutralize oxidative radicals
Name two cells that utilize NADPH for an oxidative burst.
Neutrophils, macrophages
During the oxygen-dependent respiratory burst used by neutrophils to destroy bacteria, what enzyme converts hydrogen peroxide to bleach (hypochlorite) in the presence of chloride ion?
Myeloperoxidase, which is found in neutrophil azurophilic granules
Why would you expect cells like neutrophils and macrophages to have high concentrations of NADPH oxidase?
It is important for the immune response, rapidly releasing reactive oxygen species to kill bacteria
What disease is caused by a deficiency of NADPH oxidase?
Chronic granulomatous disease; a genetic immunodeficiency
During the oxygen-dependent respiratory burst that is used by neutrophils to destroy bacteria, what enzyme converts oxygen to superoxide?
NADPH oxidase
Which form of glutathione must be readily available in the cell to remove reactive oxygen species to prevent cell lysis?
The reduced form (GSH); reducing equivalents are created in the hexose monophosphate shunt
Is glutathione reduced or oxidized when converting hydrogen peroxide to water in neutrophils?
Oxidised
Regarding the neutrophil oxygen-dependent respiratory burst, which electron carrier is used to reduce glutathione after the conversion of hydrogen peroxide to water?
NADPH
During the oxygen-dependent respiratory burst that is used by neutrophils to destroy bacteria, what enzyme converts superoxide to hydrogen peroxide?
Superoxidase dismutase
During the oxygen-dependent respiratory burst that is used by neutrophils to destroy bacteria, what enzyme converts hydrogen peroxide to water in the presence of glutathione?
Catalase
What enzyme uses NADPH to replenish reduced glutathione?
Glutathione reductase
What enzyme replenishes the NADPH used to reduce glutathione?
Glucose-6-phosphate dehydrogenase
What is the end product of the oxygen-dependent respiratory burst that is used to kill bacteria in the phagolysosome?
Bleach (HOCl, hypochlorite)
True or False? The white blood cells of patients with chronic granulomatous disease can utilize hydrogen peroxide generated by invading organisms and convert it to reactive oxygen intermediates.
True
Patients with chronic granulomatous disease are at an increased risk for infection by which microorganisms?
Catalase-positive species like Staphylococcus aureus and Aspergillus
What substance detoxifies free radicals and peroxides in the cell?
Glutathione
What molecule is required to maintain a store of reduced glutathione?
NADPH
What enzyme is required to produce and maintain NADPH within the cell?
Glucose-6-phosphate dehydrogenase
What might you find on the peripheral smear of someone with glucose-6-phosphate dehydrogenase deficiency after they consume fava beans?
Haemolytic anaemia (hence the reference to this condition as favism)
What property of fava beans, sulfonamides, primaquine, and antituberculosis drugs allows them to cause hemolytic anemia in persons with glucose-6-phosphate dehydrogenase deficiency?
They are all oxidizing agents, and cause oxidative stress to the erythrocyte
What are the precipitates of hemoglobin that are found on microscopy in the red blood cells of patients with glucose-6-phosphate dehydrogenase deficiency called?
Heinz bodies (remember: Heinz bodies = precipitated Hemoglobin)
Members of which populations are more likely to have glucose-6-phosphate dehydrogenase deficiency?
Mediterranean and African individuals
What is the most common human enzyme deficiency?
Glucose-6-phosphate dehydrogenase deficiency
Glucose-6-phosphate dehydrogenase deficiency shows what form of inheritance?
X-linked recessive; therefore, symptoms are largely seen in males
People with glucose-6-phosphate dehydrogenase deficiency have _____ (increased/decreased) malarial resistance.
increased; this likely accounts for the prevalence of the deficiency in African populations
Phagocytic removal of Heinz bodies from macrophages in patients with glucose-6-phosphate dehydrogenase deficiency results a specific appearance of red blood cells when viewed under a microscope termed ____ _____.
Bite cells
What disease is caused by a deficiency of aldolase B?
Fructose intolerance
What disease is caused by a defect in fructokinase?
Essential fructosuria
What type of disease inheritance is demonstrated in families with fructose intolerance?
Autosomal recessive
Patients with fructose intolerance accumulate what metabolic intermediate?
Fructose-1-phosphate
Which disorder of fructose metabolism involves the symptoms of hypoglycemia, jaundice, cirrhosis, and vomiting?
Fructose intolerance
Which causes milder symptoms: disorders of fructose metabolism or analogous disorders of galactose metabolism.
Disorders of fructose metabolism
Why does consumption of sucrose worsen the symptoms of fructose intolerance?
Sucrose is made of fructose and glucose
What is the mode of inheritance of fructose intolerance?
Autosomal recessive, as is the case with most enzyme deficiencies
What is the treatment for fructose intolerance?
Decreased fructose and sucrose intake
In fructose metabolism, the conversion of fructose into fructose-1-phosphate is catalyzed by what enzyme?
Fructokinase
Are patients with a deficiency of aldolase B (fructose intolerance) more likely to be hyperglycemic or hypoglycemic?
Hypoglycaemic
In fructose metabolism, the conversion of fructose-1-phosphate into dihydroxyacetone phosphate plus glyceraldehyde is catalyzed by what enzyme?
Aldolase B; the resulting molecules can enter glycolysis
Which disorder of fructose metabolism causes more serious clinical sequelae?
Fructose intolerance
What molecule becomes scarce in fructose intolerance, resulting in inhibition of glycogenolysis and gluconeogenesis?
Phosphate
Galactosemia is caused by an absence of what enzyme?
Galactose-1-phosphate uridyltransferase
Which has milder symptoms: classic galactosemia, or galactokinase deficiency?
Galactokinase deficiency
What is the inheritance pattern of galactokinase deficiency?
Autosomal recessive
What enzyme interconverts UDP-glucose and UDP-galactose?
4-Epimerase
Galactitol is formed from galactose using which enzyme?
Aldose reductase
In galactose metabolism, the conversion of galactose-1-phosphate to glucose-1-phosphate is catalyzed by which enzyme?
Galactose-1-phosphate uridyltransferase; deficiency causes classic galactosemia
In galactose metabolism, a block in the conversion of galactose to galactose-1-phosphate is caused by what disease?
Galactokinase deficiency
In galactosemia, the build-up of which substance causes damage to organs?
Galatitol
What is the treatment for galactosemia?
Removing galactose and lactose from the diet
Cataracts, hepatosplenomegaly, and mental retardation are symptoms of what disorder of galactose metabolism?
Galactosemia; it is more severe than galactokinase deficiency
In galactose metabolism, a block in the conversion of galactose-1-phosphate to glucose-1-phosphate is caused by what disease?
Galactosemia
Galactosemia demonstrates what type of inheritance pattern?
Autosomal recessive
Glucose is converted to its alcohol counterpart, sorbitol, and thus trapped in the cell via what enzyme?
Aldose reductase
Some tissues convert sorbitol to fructose via what enzyme?
Sorbitol dehydrogenase
List the organs that have both aldose reductase and sorbitol dehydrogenase
Liver, ovaries, and seminal vesicles
The enzymes aldose reductase and sorbitol dehydrogenase both require what cofactor?
NADPH
What organ has only aldose reductase and no sorbitol dehydrogenase?
Kidney
What type of cell in the nervous system has only aldose reductase and no sorbitol dehydrogenase?
Schwann cells
What parts of the eye have only aldose reductase and no sorbitol dehydrogenase?
Lens and retina
Why is sorbitol considered osmotically active?
Because of its inability to freely cross the membrane like glucose
In what disease is sorbitol accumulation common?
Diabetes
What three conditions are seen in chronic diabetes due to the osmotic damage caused by sorbitol?
Cataracts, retinopathy, peripheral neuropathy
What two sugars that are also converted to their respective alcohol forms via aldose reductase are considered osmotically active?
Fructose and galactose
Which populations tend to be lactase deficient in adulthood?
Asian and African-American populations
A woman gets bloating, cramps, and diarrhea after eating milk and ice cream. What enzyme is likely deficient in this patient?
Lactase
What is the treatment for lactase deficiency?
Lactase pills or dietary avoidance of lactose
Lactase deficiency causes what type of diarrhea when lactose is consumed?
Osmotic diarrhea due to undigested sugars that are not absorbed in the small intestine
The amino acids found in proteins in the human body are ______ (R-form/L-form).
L-form
Name the four amino acids that are both glucogenic and ketogenic.
Isoleucine, phenylalanine, threonine, and tryptophan
Name the two purely ketogenic amino acids.
Leucine and lysine
Name the four amino acids that are purely glucogenic.
Methionine, valine, arginine, and histidine
Which two amino acids become essential during periods of rapid growth?
Arginine and histidine
What type of amino acids make up histones? Why?
Basic amino acids; the positive charge interacts with the negatively charged DNA to bind it in coils
What is the significance of an amino acid being considered essential?
It must come from the diet
Name the two acidic amino acids.
Aspartate and glutamate
Through what process can glucogenic amino acids be converted to glucose?
Gluconeogenesis
Name the amino acids that are basic
Arginine, lysine and histidine
Which two amino acids are positively charged at body pH? Which are negatively charged?
Positive: arginine and lysine; Negative: aspartate and glutamate
The urea cycle ultimately yields ______, which is excreted in the urine, and _____, which can enter the citric acid cycle.
Urea; fumarate
In what organ does the urea cycle occur?
The liver
Does the urea cycle occur in the mitochondria, in the cytosol, or both?
Both
In the urea cycle, the formation of what substance occurs in the mitochondria (whereas the remaining steps occur in the cytosol)?
Carbamoyl phosphate
What amino acid is the immediate precursor to urea in the urea cycle?
Arginine
The urea cycle excretes an excess of which element generated by amino acid catabolism?
Nitrogen
What amino acid combines with citrulline to form arginosuccinate in the urea cycle?
Aspartate
What is the rate-limiting enzyme of the urea cycle?
Carbamoyl phosphate synthetase I
What reaction is catalyzed by carbamoyl phosphate synthetase I?
The conversion of CO2 and NH4 into carbamoyl phosphate, a process requiring 2 adenosine triphosphate
Where in the cell does the rate-limiting step of the urea cycle occur?
In the mitochondria
From which molecules are the nitrogen atoms in urea derived?
Ammonium and aspartate
What enzyme catalyzes the conversion of carbamoyl phosphate and ornithine into citrulline?
Ornithine transcarbamoylase
What are two metabolic fuels produced by amino acid catabolism?
Pyruvate and acetyl-CoA
What precursors are converted by arginosuccinate synthetase into arginosuccinate?
Citrulline and aspartate
What by-product of the urea cycle is released by arginosuccinase?
Fumarate, which may enter the tricarboxylic acid cycle, whereas arginine is converted into urea and ornithine in the urea cycle
What is the enzyme that creates urea from arginine in the urea cycle?
Arginase
Ammonia is transported by which amino acid from the muscle to the liver to participate in urea formation?
Alanine
Trace the pathway of an ammonium group from its creation by amino acid catabolism in muscle to excretion.
It is donated to pyruvate to form alanine, which travels to the liver via blood, where it is donated to -ketoglutarate to form glutamate, which can be excreted via the urea cycle
Ammonia groups are transported from muscle to liver via which molecule?
Alanine
What is the fate of alanine in the liver after it donates its ammonia group to the urea cycle?
It becomes pyruvate and goes through gluconeogenesis
The addition of an ammonia group to -ketoglutarate produces what substance?
Glutamate
The addition of an ammonia group to pyruvate produces what substance?
Alanine
Name two categories of hyperammonemia and examples of each.
Acquired, as in liver failure; hereditary, as in urea cycle enzyme deficiencies
Excess ammonium depletes _____, leading to inhibition of the citric acid cycle.
-Ketoglutarate
Describe the clinical presentation of hyperammonemia
Tremor, slurring of speech, somnolence, vomiting, cerebral edema, and blurring of vision
A patient presents with tremor, slurring of speech, somnolence, vomiting, cerebral edema, and blurring of vision, and is diagnosed with hyperammonemia. What two treatments could lower her serum ammonia levels?
Benzoate or phenylbutyrate
What is the most common urea cycle enzyme deficiency?
Ornithine transcarbamoylase deficiency
What is the inheritance pattern of ornithine transcarbamoylase deficiency?
X-linked recessive
You see a patient with a urea cycle enzyme deficiency, but have ruled out ornithine transcarbamoylase deficiency. What is the inheritance pattern?
Autosomal recessive (all urea cycle enzyme deficiencies except ornithine transcarbamoylase deficiency have this inheritance pattern)
How does ornithine transcarbamoylase deficiency present clinically?
Tremor, lethargy, vomiting in a neonate who may be found to have cerebral edema and elevated ammonia on lab studies
When would you most likely detect an ornithine transcarbamoylase deficiency in a patient?
Typically this is evident in the first days of life, but it may have later onset
What molecule is excess carbamoyl phosphate converted into?
Orotic acid
What serum finding is diagnostic of ornithine transcarbamoylase deficiency?
Elevated orotic acid
A newborn patient has a blood test which shows increased orotic acid, low BUN, and increased ammonia; what disease do you suspect?
Ornithine transcarbamoylase deficiency
Which amino acid is the parent compound of tyrosine, thyroxine, dopa, melanin, dopamine, norepinephrine, and epinephrine?
Phenylalanine
What amino acid is the parent compound of niacin, serotonin, and melatonin?
Tryptophan
From which amino acid is histamine derived?
Histidine
From which amino acid is haem derived?
Glycine
Which amino acid is the parent compound of creatine, urea, and nitric oxide?
Arginine
From which amino acid is γ-aminobutyric acid derived?
Glutamate
From which amino acid is porphyrin derived?
Glycine
From which amino acid are NAD+ and NADP+derived?
Tryptophan
The reaction in which GABA is derived from glutamate is catalyzed by which enzyme?
Glutamate decarboxylase; the reaction also requires vitamin B6
Dopa decarboxylase requires what cofactor? What inhibits this cofactor?
Vitamin B6; carbidopa
What cofactor does dopamine -hydroxylase require?
Vitamin C
What cofactor does phenylethanolamine N-methyltransferase require?
S-adenosylmethionine
Dopamine is broken down to homovanillic acid via what two enzymes?
Monoamine oxidase and catechol-O-methyltransferase
Monoamine oxidase and catechol-O-methyltransferase break down norepinephrine to what product?
Vanillymandelic acid
Epinephrine is broken down to what product via monoamine oxidase and catechol-O-methyltransferase?
Metanephrine
In a normal individual, is tyrosine an essential or a nonessential amino acid?
Nonessential
True or False? Phenylketonuria is a disorder of branched-chain amino acid metabolism.
False ; phenylketonuria is a disorder of aromatic amino acid metabolism (remember: aromatic amino acid metabolism = musty body odor)
What is an example of dietary phenylalanine?
Aspartame (eg, NutraSweet)
A woman with phenylketonuria learns she is pregnant; what would you advise her about her diet?
It is important to be strict about phenylalanine consumption, since it is a teratogen in women with phenylketonuria
Phenylketonuria can result from two defects: (1) decreased levels of the enzyme _____ _____ or (2) decreased levels of _____ _____.
Phenylalanine hydroxylase; tetrahydrobiopterin cofactor
In individuals with phenylketonuria, is tyrosine an essential or a nonessential amino acid?
Essential
An infant is found to have mental retardation and growth retardation. He has fair skin, eczema, and a musty body odor. What is this infant;s underlying metabolic disorder?
Phenylketonuria
What dietary modifications are used to treat phenylketonuria?
Decreasing phenylalanine and increasing tyrosine in the diet
A child has increased phenylacetate, phenyllactate, and phenylpyruvate in her urine. What is the underlying metabolic disorder?
Phenylketonuria
What type of inheritance pattern does phenylketonuria demonstrate?
Autosomal recessive
Normally, tyrosine can be made from what amino acid precursor?
Phenylalanine; however, patients with phenylketonuria lack the enzymes to carry out the reaction
What would a urinalysis show in a patient who has a deficiency of phenylalanine hydroxylase?
Elevated phenylketones
What might you see in an infant born to a mother with phenylketonuria and exposed to high in utero levels of phenylalanine?
Microcephaly, mental retardation, growth retardation, congenital heart defects
True or False? Phenylketonuria is screened for at birth.
True; it has a prevalence of 1:10,000 and is part of newborn screening in most states
A deficiency of which enzyme results in the disease alkaptonuria?
Homogentisic acid oxidase
Alkaptonuria results from a defect in the degradation of which amino acid?
Tyrosine
A patient submits a urine sample for routine urinalysis. A technician notes that it turns black upon standing. What is the underlying metabolic disorder?
Alkaptonuria
What are the signs and symptoms of alkaptonuria?
Dark connective tissue, debilitating arthralgias, pigmented sclerae
What is the prognosis for patients with alkaptonuria?
Alkaptonuria is a benign disease, although patients may suffer from arthralgias
What is the inheritance pattern of alkaptonuria?
Autosomal recessive
Albinism may be caused by a defect in the ability to synthesize melanin as a result of a deficiency in the enzyme _____, or it may result from a defect in the transporters of the amino acid _____.
Tyrosinase; tyrosine
Albinism involves decreased amounts of what substance and thus a lack of pigmentation?
Melanin
Which cells are the embryologic precursors of melanocytes?
Neural crest cells; failure of these cells to migrate results in albinism
Patients with albinism are at an increased risk for what type of cancer?
Skin cancer
How many parents must be carriers of a mutation for a child to have albinism secondary to mutated tyrosinase?
Two; this is an autosomal-recessive condition
Why does albinism show variable inheritance if it is an autosomal recessive disorder?
It exhibits locus heterogeneity
A patient with homocystinuria due to cystathionine synthase deficiency should be treated with which dietary modifications?
A diet that is low in methionine and high in cystine, vitamin B12, and folate
A patient has homocystinuria that is caused by a decreased affinity of cystathionine synthase for pyridoxal phosphate. What is the treatment?
Large doses of vitamin B6
Which amino acid, usually nonessential, becomes essential in patients with homocystinuria?
Cysteine
A defect in cystathionine synthase leads to what disorder?
Homocystinuria
A decrease in the affinity of cystathionine synthase for pyridoxal phosphate leads to what disorder?
Homocystinuria
A defect in homocysteine methyltransferase leads to what disorder?
Homocystinuria
Homocystinuria may be caused by which three defects?
A defect in cystathionine synthase, a decrease in the affinity of cystathionine synthase for its cofactor (pyridoxal phosphate), or a defect in homocystene methyltransferase
What test would you order in a patient who has advanced early atherosclerotic disease, tall stature, kyphosis, and lens subluxation?
Urine studies, looking for elevated homocysteine
A patient has mental retardation, osteoporosis, tall stature, lens subluxation, and a history of stroke and myocardial infarction. What is the underlying metabolic disorder?
Homocystinuria
What two amino acids can be produced from homocysteine?
Methionine and cysteine
The production of cysteine from homocysteine requires which vitamin as a cofactor?
Vitamin B6
What enzyme is required for the conversion of homocysteine to methionine?
Homocysteine methyltransferase
What enzyme is required for the conversion of homocysteine to cystathionine?
Cystathionine synthase
What cofactor is required for the conversion of homocysteine to methionine?
Vitamin B12
Cystinuria is a defect in an amino acid transporter that is located in which part of the body?
The proximal convoluted tubule of the kidney
What is the prevalence of cystinuria?
4.9027777778
Cystinuria is a defect in the transport of which four amino acids?
Cysteine, ornithine, lysine, and arginine
What is the major clinical sequela of cystinuria?
Increased risk of staghorn calculi
What medication is used to treat cystinuria?
Acetazolamide (carbonic anhydrase inhibitor)
What symptom is characteristic of cystinuria?
Cystine kidney stones (cystine staghorn calculi)
How does acetazolamide prevent cystine stone formation?
It alkalinizes the urine, increasing the solubility of cystine
What is the molecular structure of cystine?
Two cysteine molecules connected by a disulfide bond
What is the inheritance pattern of cystinuria?
Autosomal recessive
Maple syrup urine disease is caused by a defect in what enzyme?
-Ketoacid dehydrogenase
Maple syrup urine disease is the result of the blocked degradation of what type of amino acids?
Branched amino acids
Which three branched amino acids are elevated in the blood of a patient with maple syrup urine disease?
Isoleucine, leucine, and valine (remember: I Love Vermont maple syrup from maple trees, with branches)
What is the prognosis for a neonate diagnosed with maple syrup urine disease?
Most children with the disease die in infancy
What is Hartnup disease?
A disorder in which a defective neutral amino acid transporter leads to tryptophan wasting in the urine and gastrointestinal tract
What are the clinical signs and symptoms of Hartnup disease?
Hartnup disease causes pellagra due to inability to synthesize niacin; the result is diarrhea, dermatitis, and dementia
How is Hartnup disease inherited?
Autosomal recessive
Glucagon and epinephrine activate the second messenger cAMP via what enzyme?
Adenylyl cyclase
What two factors in muscle, by activating phosphorylase kinase, ensure that glycogenolysis is coordinated with muscle activity?
Calcium and calmodulin
What enzyme activates glycogen phosphorylase kinase?
Protein kinase A
