One Word_Biochemistry Flashcards Preview

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Flashcards in One Word_Biochemistry Deck (148):
1

α-amanitin

(found in death cap mushrooms) inhibits RNA polymerase II. Causes liver failure if ingested

2

Zinc

Function: Essential for the activity of 100+ enzymes. Important in the formation of zinc fingers (transcription factor motif) Deficiency: Delayed wound healing, hypogonadism, ↓ adult hair (axillary, facial, pubic), dysgeusia, anosmia. May predispose to alcoholic cirrhosis.

3

Type IV collagen (3)

Basement membrane or basal lamina (maybe lens?)

4

Type III collagen - Reticulin (5)

skin, blood vessels, uterus, fetal tissue, granulation tissue

5

Type II collagen (3)

Cartilage (including hyaline), vitreous body, nucleus pulposus

6

Type I collagen (7)

Bone, Skin, Tendon, dentin, fascia, cornea, late wound repair

7

Trinucleotide repeat expansion diseases

Huntington's disease = (CAG)n Myotonic dystrophy = (CTG)n Fragile X syndrome = (CGG)n Friedreich's ataxia = (GAA)n

8

Treatment: Pyruvate dehydrogenase deficiency

Lysine and Leucine - the only purely ketogenic amino acids

9

Treatment: Orotic aciduria

Oral uridine administration

10

Transversion

Substituting purine for pyrimidine or vice versa

11

Transition

Substituting purine for purine or pyrimidine for pyrimidine

12

Toxicity: Arsenic

inhibits lipoic acid, causes vomiting, rice water stools, garlic breath

13

Rate-determining enzymes of metabolic processes - Urea cycle

Carbamoyl phosphate synthetase I

14

Rate-determining enzymes of metabolic processes - TCA cycle

Isocitrate dehydrogenase

15

Rate-determining enzymes of metabolic processes - Ketogenesis

HMG-CoA synthase

16

Rate-determining enzymes of metabolic processes - HMP shunt

Glucose-6-phosphate dehydrogenase (G6PD)

17

Rate-determining enzymes of metabolic processes - Glycolysis

Phosphofructokinase-1 (PFK-1)

18

Rate-determining enzymes of metabolic processes - Glycogenolysis

Glycogen phosphorylase

19

Rate-determining enzymes of metabolic processes - Glycogen synthesis

Glycogen synthase

20

Rate-determining enzymes of metabolic processes - Gluconeogenesis

Fructose-1,6-biphosphatase

21

Rate-determining enzymes of metabolic processes - Fatty acid synthesis

Acetyl-CoA carboxylase (ACC)

22

Rate-determining enzymes of metabolic processes - Fatty acid oxidation

Carnithine acyltransferase I

23

Rate-determining enzymes of metabolic processes - De novo pyrimidine synthesis

Carbamoyl phosphate synthetase II

24

Rate-determining enzymes of metabolic processes - De novo purine synthesis

Glutamine-PRPP amidotransferase

25

Rate-determining enzymes of metabolic processes - Cholesterol synthesis

HMG-CoA reductase

26

Pyruvate dehydrogenase complex

The complex contains 3 enzymes that require 5 cofactors: 1. Pyrophosphate (B1); 2. FAD (B2); 3. NAD (B3); 4. CoA (B5); 5. Lipoic acid Activated by exercise: ↑NAD+/NADH ratio, ↑ADP, ↑Ca2+

27

Pyrimidines are made from?

Orotate precursor, with PRPP added later

28

Purines are made from?

IMP precursor

29

Prader-Willi syndrome

Deletion of normally active Paternal allele Mental retardation, hyperphagia, obesity, hypogonadism, hypotonia

30

Ornithine transcarbamoylase deficiency

(↓urea cycle), leads to an accumulation of carbamoyl phosphate, which is then converted to orotic acid

31

Octamer subunit amino acids

Lysine and Arginine

32

Nucleotide that has a methyl

Thymine

33

Nucleotide that has a ketone

Guanine

34

mRNA start codons code for?

Eukaryotes: Methionine Prokaryotes: Formyl-methionine (f-Met)

35

Molecular motor proteins: Kinesin

anterograde to microtubule

36

Molecular motor proteins: Dynein

retrograde to microtubule

37

Modes of inheritance - Mitochondrial myopathies

Mitochondrial inheritance

38

Modes of inheritance - Leber's hereditary optic neuropathy

Mitochondrial inheritance, degeneration of retinal ganglion cells and axons. Leads to acute loss of central vision.

39

Modes of inheritance - Hypophosphatemic rickets

formerly known as vitamin D resistant rickets. Inherited X-linked dominant disorder resulting in ↑ phosphate wasting at proximal tubule. Results in rickets-like presentation.

40

MOA: Trimethoprim

inhibits bacterial dihydrofolate reductase (↓dTMP)

41

MOA: Tetracyclines

bind 30S subunit, preventing attachment of aminoacyl-tRNA

42

MOA: Quabain

inhibits by binding to K+ site

43

MOA: Orotic aciduria

Inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway) due to defect in either orotic acid phosphoribosyltransferase or ototidine 5'-phosphate decarboxylase. Autosomal recessive.

44

MOA: Methotrexate (MTX)

inhibits dihydrofolate reductase (↓dTMP)

45

MOA: Macrolides

bind 50S, blocking translocation

46

MOA: Hydroxyurea

inhibits ribonucleotide reductase

47

MOA: Clindamycin

binds 50S, blocking translocation

48

MOA: Chloramphenicol

inhibits 50S peptidyltransferase

49

MOA: Cardiac glycosides (digoxin and digitoxin)

directly inhibit the Na+-K+ ATPase, which leads to indirect inhibition of Na+/Ca2+ exchange. ↑ [Ca2+]i → ↑ cardiac contractility.

50

MOA: Aminoglycosides

inhibit formation of the initiation complex and cause misreading of mRNA

51

MOA: 6-mercaptopurine (6-MP)

blocks de novo purine synthesis

52

MOA: 5-fluorouracil (5-FU)

inhibits thymidylate synthase (↓dTMP)

53

Metabolism sites - Mitochondria (4)

Fatty acid oxidation (β-oxidation), acetyl-CoA production, TCA cycle, oxidative phosphorylation

54

Metabolism sites - Cytoplasm (5)

Glycolysis, fatty acid synthesis, HMP shunt, protein synthesis (RER), steroid synthesis (SER)

55

Metabolism sites - Both (3)

Heme synthesis, Urea cycle, Gluconeogenesis (HUGs takes two)

56

Marfan's syndrome

caused by a defect in fibrillin

57

Marasmus

energy malnutrition resulting in tissue and muscle wasting, loss of subcutaneous fat, and variable edema.

58

Major apolipoproteins - E

Mediates extra (remnant) uptake

59

Major apolipoproteins - C-II

Cofactor for lipoprotein lipase

60

Major apolipoproteins - B-48

Mediates chylomicron secretion

61

Major apolipoproteins - B-100

Binds to LDL receptor, mediates VLDL secretion

62

Major apolipoproteins - A-I

Activates LCAT

63

Lysosomal storage diseases - Tay-Sachs disease

Findings: Progressive neurodegeneration, developmental delay, cherry-red spot on macula, lysosomes with onion skin, no hepatosplenomegaly (vs. Niemann-Pick) Deficient enzyme: Hexosaminidase A Accumulated substrate: GM2 ganglioside Inheritance: AR

64

Lysosomal storage diseases - Niemann-Pick disease

Findings: Progressive neurodegeneration, hepatosplenomegaly, cherry-red spot on macula, foam cells Deficient enzyme: Sphingomyelinase Accumulated substrate: Sphingomyelin Inheritance: AR

65

Lysosomal storage diseases - Metachromatic leukodystrophy

Findings: Central and peripheral demyelination with ataxia, dementia Deficient enzyme: Arylsulfatase A Accumulated substrate: Cerebroside sulfate Inheritance: AR

66

Lysosomal storage diseases - Krabbe's disease

Findings: Peripheral neuropathy, developmental delay, optic atrophy, globoid cells Deficient enzyme: Galactocerebrosidase Accumulated substrate: Galactocerebroside Inheritance: AR

67

Lysosomal storage diseases - Hurler's syndrome

Findings: Developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly Deficient enzyme: α-L-iduronidase Accumulated substrate: Heparan sulfate, dermatan sulfate Inheritance: AR

68

Lysosomal storage diseases - Hunter's syndrome

Findings: Mild Hurler's + aggressive behavior, no corneal clouding Deficient enzyme: Iduronate sulfatase Accumulated substrate: Heparan sulfate, dermatan sulfate Inheritance: XR

69

Lysosomal storage diseases - Gaucher's disease (most common)

Findings: Hepatosplenomegaly, aseptic necrosis of the femur, bone crisis, Gaucher's cells (macrophages that look like crumpled tissue paper) Deficient enzyme: β-glucocerebrosidase Accumulated substrate: Glucocerebroside Inheritance: AR

70

Lysosomal storage diseases - Fabry's disease

Findings: Peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular/renal disease Deficient enzyme: α-galactosidase A Accumulated substrate: Ceramide trihexoside Inheritance: XR

71

Liver enzyme - Pancreatic lipase

degradation of dietary TG in small intestine

72

Liver enzyme - Lipoprotein lipase (LPL)

degradation of TG circulating in chylomicrons and VLDLs

73

Liver enzyme - Hormone-sensitive lipase

degradation of TG stored in adipocytes

74

Liver enzyme - Hepatic TG lipase (HL)

degradation of TG remaining in IDL

75

Lesch-Nyhan syndrome

X-linked recessive, defective purine salvage owing to absence of HGPRT, which converts hypoxanthine to IMP and guanine to GMP. Results in excess uric acid production. Findings: retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis

76

Kwashiokor

protein malnutrition resulting in skin lesions, edema, liver function (fatty change due to ↓ apolipoprotein synthesis). Clinical picture is a small child with swollen belly. Malnutrition, Edema, Anemia, fatty Liver.

77

Kartagener's syndrome

immotile cilia due to a dynein arm defect. Results in male and female infertility (sperm immotile), bronchiectasis, and recurrent sinusitis (bacteria and particles not pushed out); associated with situs inversus

78

Imprinting

At a single locus, only 1 allele is active; the other is inactive (imprinted / inactivated by methylation). Deletion of the active allele → disease Both syndromes due to inactivation or deletion of genes on chromosome 15 Can also occur as a result of uniparental disomy

79

Immunohistochemical stains: Vimentin

Connective tissue

80

Immunohistochemical stains: Neurofilaments

Neurons

81

Immunohistochemical stains: GFAP

Neuroglia

82

Immunohistochemical stains: Desmin

Muscle

83

Immunohistochemical stains: Cytokeratin

Epithelial cells

84

I-cell disease

(inclusion cell disease) - inherited lysosomal storage disorder; failure of addition of mannose-6-phosphate to lysosome proteins (enzymes are secreted outside the cell instead of being targeted to the lysosome). Results in coarse facial features, clouded corneas, restricted joint movement, and high plasma levels of lysosomal enzymes. Often fatal in childhood.

85

Heterochromatin

Condensed, transcriptionally inactive, sterically inaccessible

86

Hardy-Weinberg law assumptions (4)

1. No mutation occuring at the locus 2. No selection for any of the genotypes at the locus 3. Completely random mating 4. No migration

87

Glycogen storage diseases - Von Gierke's disease (type I)

Findings: severe fasting hypoglycemia, ↑↑ glycogen in liver, ↑ blood lactate, hepatomegaly Deficient enzyme: Glucose-6-phosphatase

88

Glycogen storage diseases - Pompe's disease (Type II)

Findings: Cardiomegaly and systemic findings leading to early death Deficient enzyme: Lysosomal α-1,4-glucosidase (acid maltase)

89

Glycogen storage diseases - McArdle's disease (type V)

Findings: ↑ glycogen in muscle, but cannot break it down, leading to painful muscle cramps, myoglobinuria with stenuous exercise Deficient enzyme: Skeletal muscle glycogen phosphorylase

90

Glycogen storage diseases - Cori's disease (type III)

Findings: milder form of type I with normal blood lactate levels Deficient enzyme: Debranching enzyme (α-1,6-glucosidase)

91

Genetic terms: Variable expression

Nature and severity of phenotype vary from 1 individual to another

92

Genetic terms: Uniparental disomy

Offspring receives 2 copies of a chromosome from 1 parent and no copies from the other parent

93

Genetic terms: Pleiotropy

1 gene has > 1 effect on an individual's phenotype

94

Genetic terms: Mosaicism

Occurs when cells in the body have different genetic makeup. Can be a germ-line mosaic, which may produce disease that is not carried by parent's somatic cells

95

Genetic terms: Loss of heterozygosity

If a patient inherits or develops a mutation in a tumor suppressor gene, the complementary allele must be deleted/mutated before cancer develops. This is not true of oncogenes.

96

Genetic terms: Locus heterogeneity

Mutations at different loci can produce the same phenotype

97

Genetic terms: Linkage disequilibrium

Tendency for certain alleles at 2 linked loci to occur together more often than expected by chance. Measured in a population, not in a family, and often varies in different populations.

98

Genetic terms: Incomplete penetrance

Not all individuals with a mutant genotype show the mutant phenotype

99

Genetic terms: Imprinting

Differences in phenotype depend on whether the mutation is of maternal or paternal origin

100

Genetic terms: Heteroplasmy

Presence of both normal and mutated mtDNA, resulting in variable expression in mitochondial inherited disease.

101

Genetic terms: Dominant negative mutation

Exerts a dominant effect. A heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning.

102

Genetic terms: Codominance

Neither of 2 alleles is dominant

103

Genetic terms: Anticipation

Severity of disease worsens or age of onset of disease is earlier in succeeding generations

104

Genetic code features: Universal

Genetic code is conserved throughout evolution

105

Genetic code features: Unambiguous

Each codon specifies only 1 amino acid

106

Genetic code features: Degenerate / redundant

More than 1 codon may code for the same amino acid

107

Genetic code features: Commaless, nonoverlapping

Read from a fixed starting point as a continuous sequence of bases

108

Findings: Orotic aciduria

↑ orotic acid in urine, megaloblastic anemia (does not improve with administration of vitamin B12 or folic acid), failure to thrive. No hyperammonemia (vs. OTC deficiency - ↑ orotic acid with hyperammonemia)

109

Euchromatin

Less condensed, transcriptionally active, sterically accessible

110

Ethanol metabolism: Fomepizole

inhibits alcohol dehydrogenase and is an antidote for methanol of ethylene glycol poisoning

111

Ethanol metabolism: Disulfiram (Antabuse)

inhibits acetaldehyde dehydrogenase (acetaldehyde accumulates, contributing to hangover symptoms)

112

Emphysema

can be caused by α1-antitrypsin deficiency, resulting in excess elastase activity

113

Elastin

Stretchy protein within lungs, large arteries, elastic ligaments, vocal cords, ligamenta flava (connect vertebrae → relaxed and stretched conformations). √. Rich in proline and glycine, nonglycosylated forms. √. Tropoelastin with fibrillin scaffolding. √. Broken down by elastase, which is normally inhibited by α1-antitrypsin.

114

Drugs that act on microtubules

1. Mebendazole / thiabendazole (antihelminthic) 2. Griseofulvin (antifungal) 3. Vincristine / vinblastine (anti-cancer) 4. Paclitaxel (anti-breast cancer) 5. Colchicine (anti-gout)

115

DNA replication: Single-stranded binding proteins

Prevent strands from reannealing

116

DNA replication: Replication disk

Y-shaped region alond DNA template where leading and lagging strands are synthesized

117

DNA replication: Proofreads

DNA polymerase III has 5' → 3' synthesis and proofreads with 3' → 5' exonuclease DNA polymerase I excises RNA primer with 5' → 3' exonuclease

118

DNA replication: Primase

Makes an RNA primer on which DNA polymerase III can initiate replication

119

DNA replication: Origin of replication

Particular sequence in genome where DNA replication begins. May be single (prokaryotes) or multiple (eukaryotes)

120

DNA replication: Helicase

Unwinds DNA template at replication fork

121

DNA replication: DNA topoisomerases

Create a nick in the helix to relieve supercoils created during replication

122

DNA replication: DNA polymerase III

Prokaryotic only. Elongates leading strand by adding deoxynucleotides to the 3' end. Elongates lagging strand until it reaches primer of preceeding fragment. 3' → 5' exonuclease activity "proofreads" each added nucleotide

123

DNA replication: DNA polymerase I

Prokaryotic only. Degrades RNA primer and fills in the gap with DNA

124

DNA replication: DNA ligase

Seals

125

DNA repair: Nucleotide excision repair

Specific endonucleases release the oligonucleotide containing damaged bases; DNA polymerase and ligase fill and reseal the gap, respectively. Mutated in xeroderma pigmentosum

126

DNA repair: Nonhomologous end joining

Brings together 2 ends of DNA fragments. No requirement for homology

127

DNA repair: Mismatch repair

Unmethylated, newly synthesized string is recognized, mismatched nucleotides are removed, and the gap is filled and resealed. Mutated in Hereditary nonpolyposis colorectal cancer (HNPCC)

128

DNA repair: Base excision repair

Specific glycosylases recognize and remove damaged bases, AP endonuclease cuts DNA at apyrimidinic site, empty sugar is removed, and the gap is filled and resealed.

129

Cytoskeletal elements: Microtubule (5)

Cilia, flagella, mitotic spindle, neurons, centrioles

130

Cytoskeletal elements: Intermediate filaments (5)

Vimentin, desmin, cytokeratin, glial fibrillary acid proteins (GFAP), neurofilaments

131

Cytoskeletal elements: Actin and myosin (4)

Microvilli, muscle contraction, cytokinesis, adherens junctions

132

Chédiak-Higashi syndrome

microtubule polymerization defect resulting in ↓ phagocytosis. Results in recurrent pyogenic infections, partial albinism, and peripheral neuropathy

133

Carbamoyl phosphate is involved in which 2 metabolic pathways?

1. de novo pyrimidine synthesis 2. urea cycle

134

Autosomal dominant diseases - von Hippel-Lindau disease

Findings: hemangioblastomas of retina/cerebellum/medulla; about half of affected individuals develop multiple bilateral renal cell carcinomas and other tumors. Associated with deletion of VHL gene (tumor suppressor) on chromosome 3 (3p). Results in constitutive expression of HIF (transcription factor) and activation of angiogenic growth factors. Von Hippel-Lindau = 3 words for chromosome 3.

135

Autosomal dominant diseases - Tuberous sclerosis

Findings: facial lesions (adenoma sebaceum), hyperpigmented "ash leaf spots" on skin, cortical and retinal hamartomas, seizures, mental retardation, renal cysts and renal angiomyolipomas, cardiac rhabdomyomas, ↑ incidence of astrocytomas. Incomplete penetrance, variable presentation.

136

Autosomal dominant diseases - Neurofibromatosis type 2

Bilateral acoustic schwannomas, juvenile cataracts. NF2 gene on chromosome 22; type 2 = 22.

137

Autosomal dominant diseases - Neurofibromatosis type 1 (von Recklinghausen's disease)

Findings: café-au-lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas). Also marked by skeletal disorders (e.g., scoliosis) and optic pathway gliomas. On long arm of chromosome 17; 17 letters in von Recklinghausen.

138

Autosomal dominant diseases - Marfan's syndrome

Fibrillin gene mutation → connective tissue disorder affecting skeleton, heart, and eyes. Findings: tall with long extremities, pectus excavatum, hyperextensive joints, and long, tapering fingers and toes (arachnodactyly); cystic medial necrosis of aorta → aortic incompetence and dissecting aortic aneurysms; floopy mitral valve. Subluxation of lenses.

139

Autosomal dominant diseases - Huntington's disease

Findings: depression, progressive dementia, choreiform movements, caudate atrophy, and ↓ levels of GABA and ACh in the brain. Symptoms manifest in affected individuals between the ages 20 and 50. Gene located on chromosome 4; trinucleotide repeat disorder: (CAG)n. "Hunting 4 food"

140

Autosomal dominant diseases - Hereditary spherocytosis

Spheroid erythrocytes due to spectrin or ankyrin defect; hemolytic anemia; ↑ MCHC. Splenectomy is curative.

141

Autosomal dominant diseases - Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)

Inherited disorder of blood vessels. Findings: telangiectasia, recurrent epistaxis, skin discolorations, arteriovenous malformations (AVMs).

142

Autosomal dominant diseases - Familial hypercholesterolemia (hyperlipidemia type IIA)

Elevated LDL due to defective or absent LDL receptor. Heterozygotes (1:500) have cholesterol ≈ 300mg/dL. Homozygotes (very rare) have cholesterol ≈ 700+mg/dL, severe atherosclerotic disease early in life, and tendon xanthomas (classically in the Achilles tendon); MI may develop before age 20.

143

Autosomal dominant diseases - Familial adenomatous polyposis

Colon becomes covered with adenomatous polyps after puberty. Progresses to colon cancer unless resected. Mutation on chromosome 5 (APC gene); 5 letters in "polyp".

144

Autosomal dominant diseases - Autosomal-dominant polycystic kidney disease (ADPKD)

Formerly known as adult polycystic kidney disease. Always bilateral, massive enlargement of kidneys due to multiple large cysts. Patients present with flank pain, hematuria, hypertension, progressive renal failure. 90% of cases are due to mutation in APKD1 (chromosome 16; 16 letters in "polycystic kidney"). Associated with polycystic liver disease, berry aneurysms, mitral valve prolapse. Infantile form is recessive.

145

Autosomal dominant diseases - Achondroplasia

Cell-signaling defect of fibroblast growth factor (FGF) receptor 3. Results in dwarfism; short limbs, but head and trunk are normal size. Associated with advanced paternal age.

146

Angelman's syndrome

Deletion of normally active maternal allele Mental retardation, seizures, ataxia, inappropriate laughter ("happy puppet")

147

Amino acids necessary for purine synthesis

Glycine, Aspartate, Glutamine

148

Adenosine deaminase deficiency

Excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase → prevents DNA synthesis and thus ↓ lymphocyte count. One of the major causes of SCID.