Biochem Flashcards
1
Q
What is the deficiency in Niemann-Pickett Disease? What accumulates?
A
Sphingomyelinase deficiency. Sphingomylein accumulates.
2
Q
What are the clinical features of Niemann-Pickett Disease?
A
Hepatosplenomegaly, neurologic regression, cherry-red macular spot in infancy
3
Q
What causes HbC disease?
A
Missense mutation that results in glutamate residue being substituted by lysine in both beta globin chains
4
Q
List the speeds of hemoglobin movement for hemoglobin A, S, and C in electrophoresis
A
Hemoglobin A > S > C
5
Q
What causes sickle cell disease?
A
Missense mutation that result in nonpolar valine replacing a negatively charged glutamate in both beta globin chains
6
Q
List the steps of the polyol pathway
A
- aldolase reductase coverts glucose into sorbitol
2. sorbitol slowly metabolized into fructose by sorbitol dehydrogenase
7
Q
Which prokaryotic DNA polymerases have 3’ to 5’ exonuclease activity?
A
DNA polymerase I, II, and III
8
Q
Which prokaryotic DNA polymerase has 5’ to 3’ exonuclease activity and can remove RNA primers?
A
DNA polymerase I
9
Q
What do organophosphates do to acetylcholine?
A
Inhibit its breakdown, leading to state of cholinergic excess
10
Q
How does 2,3-BPG effect hemoglobin’s affinity for oxygen? Consequences of this effect?
A
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
11
Q
What causes the rubber like properties of elastin?
A
Extensive cross-linking between elastin monomers, which is facilitated by lysyl oxidase
12
Q
What forms abnormally in patients with Ehlers-Danlos Syndrome?
A
Collagen
13
Q
How does Ehlers-Danlos Syndrome manifest?
A
Hypermobile joints, hyperelastic skin, and fragile tissue susceptible to bruising, wounding, and hemarthrosis
14
Q
What causes Marfan syndrome?
A
Inherited defect in fibrillin-1, an extracellular glycoprotein that acts as a scaffold for elastin
15
Q
Which enzyme is deficient in classic galactosemia?
A
Galactose-1-phosphate uridyl transferase
16
Q
What are the symptoms of classic galactosemia?
A
Vomiting, lethargy, jaundice, E.coli sepsis
17
Q
What is the treatment for classic galactosemia?
A
Cessation of breastfeeding and switching to soy based formula
18
Q
Fibrates inhibit which enzyme?
A
Cholesterol 7alpha-hydroxylase. Can lead to cholesterol stones
19
Q
What is deficient in hereditary fructose intolerance? What accumulates?
A
Aldolase-B is deficient. Toxic metabolite fructose-1-phosphate accumulates
20
Q
What clinical effects are seen in hereditary fructose intolerance?
A
Hypoglycemia and vomiting when fructose or sucrose is consumed
21
Q
Describe the Haldane effect
A
In the lungs, the binding of oxygen to hemoglobin drives the release of H+ and CO2 from hemoglobin
22
Q
Describe the Bohr effect
A
In the peripheral tissues, high concentrations of CO2 and H+ facilitate oxygen unloading from hemoglobin
23
Q
What causes porphyria cutanea tarda (PCT)?
A
Uroporphyrinogen decarboxylase deficiency
24
Q
How does porphyria cutanea tara present?
A
Photosensitivity, which manifests as vesicle and blister formation on sun exposed areas as well as edema, erythema, pruritus, and pain
25
Which cofactor is used for carboxylase enzymes?
Biotin (Vitamin B7)
26
Ingestion of what has been associated with a biotin deficiency?
Excess ingestion of avidin, found in raw egg whites
27
What are the clinical features of a biotin deficiency?
Mental status changes, myalgias, anorexia, macular dermatitis, and lactic acidosis
28
What process does acidosis stimulate in the kidneys?
Renal ammoniagenesis, a process by which renal tubular epithelial cells metabolize glutamine to glutamate, generating ammonium
29
What is defective in maple syrup urine disease?
Breakdown of branched chain amino acids
30
Which co-enzymes are required by branched chain alpha-ketoacid dehydrogenase complex?
Thiamine, Lipoate, Coenzyme A, FAD, NAD
31
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)
32
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
33
Which enzymes are inhibited by lead?
Ferrochelatase and ALA Dehydratase
34
What stimulates glycogenolysis in skeletal muscle?
Increased intracellular calcium
35
What causes homocystinuria?
Defect in cystathionine synthase
36
Which amino acid is essential in patients with homocystinuria?
Cysteine
37
Which inherited hyperlipoproteinemia is characterized by xanthomas and premature coronary and peripheral vascular disease
Familial dysbetalipoproteinemia
38
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
39
Which enzyme is deficient in propionic acidemia?
Propionyl-CoA Carboxylase
40
How does propionic acidemia present?
Lethargy, poor feeding, vomiting, and hypotonia 1-2 weeks after birth
41
Which enzyme is deficient in Fabry disease?
Alpha-galactosidase A
42
What accumulates in Fabry disease?
Globotriaosylceramide (Gb3)
43
Symptoms of Fabry disease?
Neuropathic pain, hypohidrosis, angiokeratomas, telangiectasias, cerebrovascular and cardiac diseases, renal failure
44
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)
45
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
46
What is a common cause of brown pigmented gallstones in East Asian countries?
The liver fluke sinensis
47
What are brown pigmented gallstones made up of?
Calcium salts and unconjugated bilirubin
48
What enzyme plays an important role in pathogenesis of brown pigment gallstones?
Beta-glucoronidase
49
What do proteins destined for the lysosome require?
Phosphorylation of specific mannose residues to ensure proper transit through the golgi apparatus
50
What enzyme catalyzes the phosphorylation of mannose residues on lysosome bound proteins?
Golgi body phosphotransferase enzyme
51
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
52
What cofactor is required for transaminase enzymes?
Pyridoxine (Vit B6)
53
What disorders are characterized by impaired ability to oxidize VLCFAs?
Peroxisomal disorders
54
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
55
Why do maturing erythrocytes lose their ability to synthesize heme?
They lose their mitochondria, which are necessary for heme synthesis
56
What is the enzyme deficiency in PKU?
Phenylalanine hydroxylase or its cofactor tetrahydrobiopterin
57
How does PKU present?
Severe intellectual disability and seizures if left untreated. Hypopigmentation of the skin, hair, eyes, and catecholaminergic brain nuclei
58
What accumulates in PKU?
Phenylalanine accumulates in body fluids and the CNS
59
What causes methylmalonic acidemia?
Autosomal recessive complete or partial deficiency of the enzyme methylmalonyl-CoA mutase
60
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
61
Which substance directly stimulates the first enzyme involved in gluconeogenesis?
Acetyl-CoA
62
What are the hallmark effects of phenylketonuria?
Intellectual disability, serotonin deficiency, and hyperphenylalanemia
63
Which enzyme is deficient in acute intermittent porphyris?
Porphobilinogen deaminase
64
What are the findings with acute intermittent porphyria?
Abdominal pain, neurological manifestations, and port wine colored urine. PBG & ALA in urine. No photosensitivity
65
How are acute intermittent porphyria attacks managed?
Glucose or hemin inhibits ALA synthase activity
66
What is used to treat cyanide poisoning?
Nitrites because they can induce methemoglobinemia (Fe3+ instead of Fe2+)
67
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
68
What causes pellegra? What are the symptoms?
Deficiency of niacin (Vit B3). Dermatitis, diarrhea, and dementia
69
Niacin is synthesized endogenously from which what precursor?
Tryptophan
70
What is the most abundant amino acid in collagen?
Glycine. Occupies every 3rd amino acid position in the alpha chain
71
What are the symptoms of riboflavin (Vit B2) deficiency?
Angular stomatitis, cheilitis, glossitis, seborrheic dermatitis, keratitis, corneal neovascularization, and anemia
72
Who typically presents with riboflavin deficiency?
Chronic alcoholics and the severely malnourished
73
What are the symptoms of Vitamin C deficiency?
Capillary bleeding, poor wound healing, periodontal disease. Bony deformities and subperiosteal hemorrhages in children.
74
What is Vitamin C required for?
Hydroxylation of proline and lysine resides in pro-collagen
75
What causes alkaptonuria?
Autosomal recessive disorder of tyrosine metabolism leading to accumulation of homogentistic acid
76
What are clinical features of alkaptonuria?
Black urine color when exposed to air, a blue-black pigment to the face, and ochronotic arthropathy
77
What amino acid is esswntial in PKU?
Tyrosine
78
What are the clinical features of PKU?
Intellectual disability, seizures, light pigmentation, and a "musty" odor
79
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
80
How does Pompe disease present?
Presents in early infancy with cardiomegaly, macroglossia, and profound muscular hypotonia
81
What enzyme deficiency causes Pompe disease?
Acid maltase (acid alpha-glucosidase)
82
What is seen on muscle biopsy in Pompe disease?
Glycogen accumulation within lysosomal vesicles
83
What can cause hyperhomocysteinemia?
MTHFR deficiency or deficiencies of B vitamins cobalamin, pyridoxine, and folate
84
Name the antioxidant enzymes
Superoxide dismutase, glutathione peroxidase, catalase
85
Describe pellagra
Photosensitive dermatitis, diarrhea, and dementia occurring secondary to vitamin B3 (Niacin) deficiency
86
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
87
Which enzyme converts pyruvate to acetyl coenzyme A?
Pyruvate dehydrogenase
88
Which motor protein mediates anterograde axonal transport?
Kinesin
89
What conditions promote sickling in sickle cell anemia?
Low oxygen levels, increased acidity, or low blood volume
90
Which disorders are associated with a mutation in JAK2 and activation of STAT proteins?
Chronic myeloproliferative disorders (Polycythemia vera, essential thrombocytosis, primary myelofibrosis)
91
Which amino acids can provide energy without increasing lactate production?
Exclusively ketogenic amino acids - lysine and leucine
92
How do patients with essential fructosuria metabolize fructose?
Some is converted by hexokinase to fructose-6-phosphate, which can enter glycolysis
93
Which hormone contributes to glucose homeostasis during prolonged fasting and has receptors found within the cytoplasm?
Cortisol
94
What deficiency can cause Ehlers-Danlos syndrome?
Procollagen peptidase deficiency, which results in impaired cleavage of terminal propeptides in the extracellular space
95
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
96
What causes the greenish color to develop in bruises?
Heme oxygenase converts heme to biliverdin
97
If subunits of hemoglobin are separated, what does their oxygen-dissociation curve look like?
Hyperbolic, similar to that of myoglobin
98
How can thiamine deficiency be diagnosed?
If baseline erythrocyte transketolase activity is low but increased after addition of thiamine pyrophosphate
99
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
100
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
101
Cause of homocystinuria
Autosomal recessive deficiency of cystathionine beta-synthase, an enzyme requiring pyridoxine (B6) as a cofactor.
102
How is homocystinuria treated?
~50% of affected patients respond to high doses of pyridoxine. Additional treatment includes dietary restriction of methionine
103
During catabolism of proteins, where are amino acid groups transferred?
To alpha-ketoglutarate
104
Increased levels of which substance inhibits beta oxidation of fatty acids?
Malonyl-CoA
105
What does ethanol inhibit?
Gluconeogenesis - can cause hypoglycemia once hepatic glycogen stores are depleted
106
Intellectual disability, gait or posture abnormality, eczema, musty body odor
Phenylketonuria (PKU)
107
PKU mutation
The gene that codes for phenylalanine hydroxylase
108
Deficiency in maple syrup urine disease?
Branched chain alpha-ketoacid dehydrogenase complex
109
How is maple syrup urine disease diagnosis confirmed?
Presence of elevated branched-chain amino acid levels
110
Therapy for maple syrup urine disease
Dietary restriction of branched chain amino acids - leucine, isoleucine, valine
111
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
112
What sequence on tRNA is used as a recognition sequence by proteins?
CCA
113
Thiamine deficiency
Vit B1. Deficiency causes beriberi and Wernicke-Korsakoff syndrome.
114
What causes essential fructosuria?
Fructokinase deficiency
115
How is some of the fructose load converted in pts with essential fructosuria?
By hexokinase to fructose-6-phosphate
116
Elevated levels of methylmalonic acid and homocysteine
Vit B12 deficiency
117
Ras is only active when bound by which substance?
GTP
118
Which enzyme is usually deficient with impaired beta oxidation of fatty acids?
Acyl-CoA dehydrogenase
