Biochem Flashcards
What is the deficiency in Niemann-Pickett Disease? What accumulates?
Sphingomyelinase deficiency. Sphingomylein accumulates.
What are the clinical features of Niemann-Pickett Disease?
Hepatosplenomegaly, neurologic regression, cherry-red macular spot in infancy
What causes HbC disease?
Missense mutation that results in glutamate residue being substituted by lysine in both beta globin chains
List the speeds of hemoglobin movement for hemoglobin A, S, and C in electrophoresis
Hemoglobin A > S > C
What causes sickle cell disease?
Missense mutation that result in nonpolar valine replacing a negatively charged glutamate in both beta globin chains
List the steps of the polyol pathway
- aldolase reductase coverts glucose into sorbitol
2. sorbitol slowly metabolized into fructose by sorbitol dehydrogenase
Which prokaryotic DNA polymerases have 3’ to 5’ exonuclease activity?
DNA polymerase I, II, and III
Which prokaryotic DNA polymerase has 5’ to 3’ exonuclease activity and can remove RNA primers?
DNA polymerase I
What do organophosphates do to acetylcholine?
Inhibit its breakdown, leading to state of cholinergic excess
How does 2,3-BPG effect hemoglobin’s affinity for oxygen? Consequences of this effect?
It allosterically decreases hemoglobin’s affinity for oxygen. In the presence of low oxygen, higher 2,3-BPG enables increased oxygen delivery to the tissues
What causes the rubber like properties of elastin?
Extensive cross-linking between elastin monomers, which is facilitated by lysyl oxidase
What forms abnormally in patients with Ehlers-Danlos Syndrome?
Collagen
How does Ehlers-Danlos Syndrome manifest?
Hypermobile joints, hyperelastic skin, and fragile tissue susceptible to bruising, wounding, and hemarthrosis
What causes Marfan syndrome?
Inherited defect in fibrillin-1, an extracellular glycoprotein that acts as a scaffold for elastin
Which enzyme is deficient in classic galactosemia?
Galactose-1-phosphate uridyl transferase
What are the symptoms of classic galactosemia?
Vomiting, lethargy, jaundice, E.coli sepsis
What is the treatment for classic galactosemia?
Cessation of breastfeeding and switching to soy based formula
Fibrates inhibit which enzyme?
Cholesterol 7alpha-hydroxylase. Can lead to cholesterol stones
What is deficient in hereditary fructose intolerance? What accumulates?
Aldolase-B is deficient. Toxic metabolite fructose-1-phosphate accumulates
What clinical effects are seen in hereditary fructose intolerance?
Hypoglycemia and vomiting when fructose or sucrose is consumed
Describe the Haldane effect
In the lungs, the binding of oxygen to hemoglobin drives the release of H+ and CO2 from hemoglobin
Describe the Bohr effect
In the peripheral tissues, high concentrations of CO2 and H+ facilitate oxygen unloading from hemoglobin
What causes porphyria cutanea tarda (PCT)?
Uroporphyrinogen decarboxylase deficiency
How does porphyria cutanea tara present?
Photosensitivity, which manifests as vesicle and blister formation on sun exposed areas as well as edema, erythema, pruritus, and pain
Which cofactor is used for carboxylase enzymes?
Biotin (Vitamin B7)
Ingestion of what has been associated with a biotin deficiency?
Excess ingestion of avidin, found in raw egg whites
What are the clinical features of a biotin deficiency?
Mental status changes, myalgias, anorexia, macular dermatitis, and lactic acidosis
What process does acidosis stimulate in the kidneys?
Renal ammoniagenesis, a process by which renal tubular epithelial cells metabolize glutamine to glutamate, generating ammonium
What is defective in maple syrup urine disease?
Breakdown of branched chain amino acids
Which co-enzymes are required by branched chain alpha-ketoacid dehydrogenase complex?
Thiamine, Lipoate, Coenzyme A, FAD, NAD
What are the clinical features of Maple Syrup Urine Disease?
Neurotoxicity that includes seizures, irritability, lethargy, and poor feeding. Sweet odor to urine (from metabolite of isoleucine)
How is Maple Syrup Urine Disease treated?
Some patients improve with high dose thiamine treatment but most require lifelong restriction of leucine, isoleucine, and valine
Which enzymes are inhibited by lead?
Ferrochelatase and ALA Dehydratase
What stimulates glycogenolysis in skeletal muscle?
Increased intracellular calcium
What causes homocystinuria?
Defect in cystathionine synthase
Which amino acid is essential in patients with homocystinuria?
Cysteine
Which inherited hyperlipoproteinemia is characterized by xanthomas and premature coronary and peripheral vascular disease
Familial dysbetalipoproteinemia
Describe the defect in familial dysbetalipoproteinemia
Defects in ApoE3 and ApoE4 lead to decreased clearance of chylomicrons and VLDL remnants causing elevated triglyceride and cholesterol levels
Which enzyme is deficient in propionic acidemia?
Propionyl-CoA Carboxylase
How does propionic acidemia present?
Lethargy, poor feeding, vomiting, and hypotonia 1-2 weeks after birth
Which enzyme is deficient in Fabry disease?
Alpha-galactosidase A
What accumulates in Fabry disease?
Globotriaosylceramide (Gb3)
Symptoms of Fabry disease?
Neuropathic pain, hypohidrosis, angiokeratomas, telangiectasias, cerebrovascular and cardiac diseases, renal failure
What makes up the transmembrane domain of a G protein-coupled receptor?
Nonpolar, hydrophobic amino acids (alanine, valine, leucine, isoleucine, phenylalanine, tryptophan methionine, proline, glycine)
What is the function of the amino acids that make up the transmembrane domain of a G protein coupled receptor?
Anchor the transmembrane region of the protein to the hydrophobic core of the phospholipid bilayer
What is a common cause of brown pigmented gallstones in East Asian countries?
The liver fluke sinensis
What are brown pigmented gallstones made up of?
Calcium salts and unconjugated bilirubin
What enzyme plays an important role in pathogenesis of brown pigment gallstones?
Beta-glucoronidase
What do proteins destined for the lysosome require?
Phosphorylation of specific mannose residues to ensure proper transit through the golgi apparatus
What enzyme catalyzes the phosphorylation of mannose residues on lysosome bound proteins?
Golgi body phosphotransferase enzyme
What are the symptoms of inclusion cell disease?
Failure to thrive, cognitive deficits in the first year of life, and characteristic facial features such as coarse facial features and corneal clouding
What cofactor is required for transaminase enzymes?
Pyridoxine (Vit B6)
What disorders are characterized by impaired ability to oxidize VLCFAs?
Peroxisomal disorders
How does Zellweger syndrome present?
Presents in early infancy with craniofacial abnormalities (widened sutures, large anterior fontanelle), hepatomegaly, and profound neurologic defects (hypotonia, seizures, developmental delay). Death usually occurs withing months of inital presentation
Why do maturing erythrocytes lose their ability to synthesize heme?
They lose their mitochondria, which are necessary for heme synthesis
What is the enzyme deficiency in PKU?
Phenylalanine hydroxylase or its cofactor tetrahydrobiopterin
How does PKU present?
Severe intellectual disability and seizures if left untreated. Hypopigmentation of the skin, hair, eyes, and catecholaminergic brain nuclei
What accumulates in PKU?
Phenylalanine accumulates in body fluids and the CNS
What causes methylmalonic acidemia?
Autosomal recessive complete or partial deficiency of the enzyme methylmalonyl-CoA mutase
How does methylmalonic acidemia present?
Lethargy, vomiting, and tachypnea in a newborn. Labs show metabolic acidosis, ketotic hypoglycemia, and hyperammonemia. Elevated urine methylmalonic acid and propionic acid
Which substance directly stimulates the first enzyme involved in gluconeogenesis?
Acetyl-CoA
What are the hallmark effects of phenylketonuria?
Intellectual disability, serotonin deficiency, and hyperphenylalanemia
Which enzyme is deficient in acute intermittent porphyris?
Porphobilinogen deaminase
What are the findings with acute intermittent porphyria?
Abdominal pain, neurological manifestations, and port wine colored urine. PBG & ALA in urine. No photosensitivity
How are acute intermittent porphyria attacks managed?
Glucose or hemin inhibits ALA synthase activity
What is used to treat cyanide poisoning?
Nitrites because they can induce methemoglobinemia (Fe3+ instead of Fe2+)
Why does pyruvate kinase deficiency result in splenomegaly?
Pyruvate kinase deficiency causes hemolytic anemia. Splenic hyperplasia results from increased work of the splenic parenchyma, which remove the deformed erythrocytes from circulation
What causes pellegra? What are the symptoms?
Deficiency of niacin (Vit B3). Dermatitis, diarrhea, and dementia
Niacin is synthesized endogenously from which what precursor?
Tryptophan
What is the most abundant amino acid in collagen?
Glycine. Occupies every 3rd amino acid position in the alpha chain
What are the symptoms of riboflavin (Vit B2) deficiency?
Angular stomatitis, cheilitis, glossitis, seborrheic dermatitis, keratitis, corneal neovascularization, and anemia
Who typically presents with riboflavin deficiency?
Chronic alcoholics and the severely malnourished
What are the symptoms of Vitamin C deficiency?
Capillary bleeding, poor wound healing, periodontal disease. Bony deformities and subperiosteal hemorrhages in children.
What is Vitamin C required for?
Hydroxylation of proline and lysine resides in pro-collagen
What causes alkaptonuria?
Autosomal recessive disorder of tyrosine metabolism leading to accumulation of homogentistic acid
What are clinical features of alkaptonuria?
Black urine color when exposed to air, a blue-black pigment to the face, and ochronotic arthropathy
What amino acid is esswntial in PKU?
Tyrosine
What are the clinical features of PKU?
Intellectual disability, seizures, light pigmentation, and a “musty” odor
Nutritional restriction of which of the following substances can improve ornithine translocase deficiency?
Protein restriction improves the condition by reducing the amount of amino acid turnover
How does Pompe disease present?
Presents in early infancy with cardiomegaly, macroglossia, and profound muscular hypotonia
What enzyme deficiency causes Pompe disease?
Acid maltase (acid alpha-glucosidase)
What is seen on muscle biopsy in Pompe disease?
Glycogen accumulation within lysosomal vesicles
What can cause hyperhomocysteinemia?
MTHFR deficiency or deficiencies of B vitamins cobalamin, pyridoxine, and folate
Name the antioxidant enzymes
Superoxide dismutase, glutathione peroxidase, catalase
Describe pellagra
Photosensitive dermatitis, diarrhea, and dementia occurring secondary to vitamin B3 (Niacin) deficiency
What is Niacin a precursor for? Where are these used as cofactors?
Precursor for NAD and NADP which are important co-enzymes for many dehydrogenase and reductase enzymes
Which enzyme converts pyruvate to acetyl coenzyme A?
Pyruvate dehydrogenase
Which motor protein mediates anterograde axonal transport?
Kinesin
What conditions promote sickling in sickle cell anemia?
Low oxygen levels, increased acidity, or low blood volume
Which disorders are associated with a mutation in JAK2 and activation of STAT proteins?
Chronic myeloproliferative disorders (Polycythemia vera, essential thrombocytosis, primary myelofibrosis)
Which amino acids can provide energy without increasing lactate production?
Exclusively ketogenic amino acids - lysine and leucine
How do patients with essential fructosuria metabolize fructose?
Some is converted by hexokinase to fructose-6-phosphate, which can enter glycolysis
Which hormone contributes to glucose homeostasis during prolonged fasting and has receptors found within the cytoplasm?
Cortisol
What deficiency can cause Ehlers-Danlos syndrome?
Procollagen peptidase deficiency, which results in impaired cleavage of terminal propeptides in the extracellular space
Which pathway does glucose-6-phosphate dehydrogenase participate in?
Rate-limiting enzyme in pentose phosphate pathway, the major source of cellular NAPDH. NADPH is necessary for reducing glutathione and for biosynthesis of cholesterol, fatty acids, and steroids
What causes the greenish color to develop in bruises?
Heme oxygenase converts heme to biliverdin
If subunits of hemoglobin are separated, what does their oxygen-dissociation curve look like?
Hyperbolic, similar to that of myoglobin
How can thiamine deficiency be diagnosed?
If baseline erythrocyte transketolase activity is low but increased after addition of thiamine pyrophosphate
What step in the citric acid cycle synthesis GTP?
Synthesized by succinyl-CoA synthetase during conversion of succinyl-CoA to succinate in the citric acid cycle
What are the clinical manifestations of homocystinuria?
Ectopic lentis, intellectual disability, marfanoid habitus. Pts are at high risk for thromboembolic occlusion, especially in brain, heart, and kidneys
Cause of homocystinuria
Autosomal recessive deficiency of cystathionine beta-synthase, an enzyme requiring pyridoxine (B6) as a cofactor.
How is homocystinuria treated?
~50% of affected patients respond to high doses of pyridoxine. Additional treatment includes dietary restriction of methionine
During catabolism of proteins, where are amino acid groups transferred?
To alpha-ketoglutarate
Increased levels of which substance inhibits beta oxidation of fatty acids?
Malonyl-CoA
What does ethanol inhibit?
Gluconeogenesis - can cause hypoglycemia once hepatic glycogen stores are depleted
Intellectual disability, gait or posture abnormality, eczema, musty body odor
Phenylketonuria (PKU)
PKU mutation
The gene that codes for phenylalanine hydroxylase
Deficiency in maple syrup urine disease?
Branched chain alpha-ketoacid dehydrogenase complex
How is maple syrup urine disease diagnosis confirmed?
Presence of elevated branched-chain amino acid levels
Therapy for maple syrup urine disease
Dietary restriction of branched chain amino acids - leucine, isoleucine, valine
Describe the PI3K/Akt/mTOR pathway
Intracellular signaling pathway important for anti-apoptosis, cellular proliferation, and angiogenesis. Mutations that enhance this pathway contribute to cancer pathogenesis
What sequence on tRNA is used as a recognition sequence by proteins?
CCA
Thiamine deficiency
Vit B1. Deficiency causes beriberi and Wernicke-Korsakoff syndrome.
What causes essential fructosuria?
Fructokinase deficiency
How is some of the fructose load converted in pts with essential fructosuria?
By hexokinase to fructose-6-phosphate
Elevated levels of methylmalonic acid and homocysteine
Vit B12 deficiency
Ras is only active when bound by which substance?
GTP
Which enzyme is usually deficient with impaired beta oxidation of fatty acids?
Acyl-CoA dehydrogenase
