Biochem Flashcards Preview

Step 1 > Biochem > Flashcards

Flashcards in Biochem Deck (125)
1

Orotic aciduria

Inability to convert orotic acid --> UMP (pyrimidine synthesis)

Sx: Inc orotic acid in urine
megaloblastic anemia (does NOT improve w/ B12)
NO hyperammonemia (vs. OTC)

2

Adenosine deaminase deficiency

AR

Accumulation of adenosine, ATP, dATP
dATP inhibits Ribonucleotide reductase --> inhibits DNA synthesis --> dysfxn T & B-cells

SCID

3

SELF-MUTILATION
Gout
Choreoathetosis
Retardation

Lesch-Nyan syndrome
- HGPRT deficiency
- Guanine & hypoxanthine can't --> GMP & IMP = Gets degraded to uric acid --> hyperuricemia
- Excess IMP & GMP --> excess purines --> CNS damage

4

Nucleotide excision repair defect

Xeroderm pigmentosum

5

Mutation of DNA mismatch repair

Hereditary Nonpolyposis Colorectal Cancer (HNPCC)
- AD
- recognizes UNmethylated new strand mismatches
- 80% --> CRC
- PROXIMAL colon alway involved

6

Cerebellar (ataxia)
Spider angiomas
IgA deficiency

Ataxia telangiectasia
- ATM gene - DNA repair enzymes

7

alpha-amantin

Inhibits RNA Pol II (mRNA)

Found in death cap mushrooms --> liver failure

8

Aminoglycosides

Bind 30S
Inhibits formation of initiation --> misread mRNA

9

Chloramphenicol

Inhibits 50S peptidyl transferase

10

Macrolides

Binds 50S --> Blocks translocation

11

Clindamycin & Chloramphenicol block?

Peptide bond formation

12

Tetracyclines

Bind 30S
Prevent aminoacyl-tRNA synthetase attachment

13

I-Cell Disease

Inherited lysosomal storage disorder

Failure to + Mannose-6-Phosphate --> secrete enzymes vs. --> lysosome

Sx:
Coarse facial features
Clouded corneas
Restricted joints

Fatal in childhood

14

Pyogenic infections - staph, strep
Albinism
Peripheral neuropathy

Chediak-Higashi Syndrome
- Failure of phagosome & lysosome fusion
- Defect Lysosomal Regulator Trafficking gene (LYST) = microtubule polymerization
- AR

15

Kartagener's Syndrome

Dynein arm defect (retro --> -)
Immoble cilia

Infertility
Bronchiectasis
Recurrent sinusitis
Assoc w/ situs inversus

16

Oubain

Inhibits binding to K+ site --> inhibits Na/K pump

17

Cardiac glycoside MOA

Inhibit Na/K pump --> inhibits Na/Ca exchange --> Inc Ca --> Inc contractility

18

Scurvy

Lack of Vit C

Required for hydroxylation of collagen w/ proline or lysine

19

Type I collagen defect

Osteogenesis imperfecta
Type I = AD
Type II = Fatal

Type I collagen (glycosylation)
1. Multiple fx
2. Blue sclera
3. Hearing loss
4. Dental imperfections

20

Type III Collagen defect

Ehlers-Danlos
Type III collagen defect (cross-linking)

1. Hyperextensible joints
2. Easy bruising
3. Berry anyuerysms
4. Hyper mobile joints/dislocation

21

Basket-weave GBM, Type IV collagen defect

Alport syndrome

1. Deafness
2. Nephritis
3. Ocular disturbances

22

Defect in Fibrillin

Marfan's Syndrome
- Tall w/ long extremities
- Pectus excavatum
- Long, tapering fingers & toes (Arachnodactyly)
- Medial necrosis of aorta --> dissecting AAs & aortic insufficiency
- Floppy mitral valve
- Subluxation of lens

Locus heterogeneity w/ MEN 2B, homocystinuria

23

alpha-1 anti-trypsin deficiency

Misfolded protein aggregates in heptocyte ER --> cirrhosis
PAS + globules in liver

Dec elastic tissu in lungs --> PANACINAR emphysema

Codominant trait

24

Southern Blot

DNA

25

Southwestern Blot

DNA-binding proteins (transcription factors)

26

Microarray

Level of gene expression

27

ELISA

Ag-Ab reactivity

28

FISH

Localization of genes & visualize anomalies

Fluorescence = gene present

29

Incomplete penetrance

Not everyone w/ mutation shows sx

30

Pleiotropy

1 gene >1 effect

PKU

31

Loss of heterogeneity

Mutation in tumor suppressor gene - complimentary allele must be deleted --> cancer

32

Mosaicism

Cells in body differ d/t POST-fertilization loss of genetic material

germ-line --> disease not in parent's cells

33

Hyperphagia, hypogonadism, hypotonia, Paternal deletion

Prader-Willi
- should be active

Maternal in inactivated

34

Seizures, ataxia, inappropriate laughter "happy puppet," maternal deletion

Angleman Syndrome
- should be active

Paternal inactive

35

AR trait

1 generation
2-carrier parents

36

XR trait

No male-to-male
More severe in males

Sons of heterozygous mothers = 50%

37

XD trait

ALL females of affected father
Both MF affected

38

FGFR3 mutation

Achondroplasia
- enchondral ossification

Dwarfism
Short limbs
NORMAL trunk & head
Normal lifespan & fertility

Assoc w/ advanced paternal age
AD & sporadic

39

AD Polycystic Kidney Disease

Adults
BILATERAL MASSIVE kidneys

PKD1 - Chr16
Polycystic liver
Berry aneurysm
MVP

40

AR Polycystic Kidney Disease

Infantile
Congenital hepatic fibrosis & Liver cysts
Portal HTN
HTN

41

Familial Adenomatous Polyposis

APC gene - chr5 (5 letters in polyp)

Polyps after puberty --> cancer

42

Familial hypercholesterolinemia

Defect/absent LDL receptor --> inc LDL

Achilles tendon xanthomas
Severe atherosclerosis -->MI b4 20

43

Osler-Weber-Rendu (Herediatry telangiectasia)

Telangiectasias
Recurrent epistaxis
Skin discolorations
AVMs

44

Hereditary spherocytosis

Spectrin or Ankyrin defect

Inc MCHC

Cure = splenectomy

45

Huntington

CAG expansion
Chr4 (hunting 4 food)

caudate atrophy --> dec GABA & Ach
Choreiform movements, progressive dementia

46

Multiple endocrine neoplasias (MEN) gene mutation

MEN 2A/B - RET gene

47

Lisch-nodules
Cafe-au-lait
Neural tumors
Scoliosis

Neurofibromatosis Type I

48

B/L Acoustic schwannoma
Juvenile cataracts

Neurofibromatosis Type II
NF2 gene - chr22

2 ears - NF2 - Chr22

49

Facial acne, hypopigmented lesion mainly on trunk, Hammartomas, Renal angiomyolipomas, Cardiac rhabdomyomas

Tuberous sclerosis
- adenoma sebaceum
- "ash leaf" spots
- Inc astrocytomas

50

B/L renal cell carcinomas
Hemangioblastomas of retina, cerebellum, medulla

Von Hippel-Lindau Disease
- VHL gene on Chr3p

51

Recurrent pulmonary infections w/ PA & SA, Pancreatic insufficiency --> malabs of fat soluble vitamins, steatorrhea, FTT

AR CFTR gene
Chronic bronchitis
Bronchiectasis
Infertility

Inc Cl- sweat test

Tx = *NAC* to loosen mucus plugs

52

Pelvic girdle --> superiorly
Hypertrophy of calves
Gower's maneuver

Duchenne's Muscular dystrophy
- Frame-shift --> Deleted Dystrophin gene (DMD) --> muscle breakdown
- longest gene in body = high mutation rate

Dx: inc CPK & biopsy

53

MACRO-orchidism, long face, large jaw, MR

Fragile-X syndrome
- FMR1 gene methylation & expression
- CGG repeat

2nd most common cause of MR (Down)

Fragile-X - Xtra large testes

54

Down syndrome

Trisomy 21

Flat facies
Prominent epicathal folds
Simian crease
Duodenal atresia
ASD
Inc ALL & Alzheimer

Inc beta-hCG

US = Inc nuchal translucency

55

Trisomy 18

Edward's syndrome (Election age 18)

Rocker-bottom feet
Micrognathia
Clenched hands

Death w/in 1yr

DEC beta-hCG

56

Trisomy 13

Patau syndrome (Puberty 13)

Rocker-bottom feet
MicroOPHTHALMIA
Cleft liP/Palate
HoloProsencephaly
Polydactyly

NORMAL enzyme levels

57

Robertsonian

Chr 13, 14, 15, 21, 22

2 acrocentric long arms fuse
2 short arms lost

58

Cri-du-chat

Deletion of short arm of chr5 (46, XX or XY, 5p-)

High pitched cry/mew
Epicanthal folds
VSD
Microcephaly

59

Williams syndrome

Deletion of long chr7

"Elfin" facies
HyperCa
EXTREME FRIENDLINESS w/ strangers

60

Vitamin A (retinol)

Source: liver, leafy vegetables

Deficiency: night blindness

Excess: Teratogenic, alopecia, fatigue

61

Vitamin B1

Thiamine

decarboxylation rxns --> ATP synthesis

Wernicke-korsakoff
Ber1-Ber1

62

Wernicke-Korsakoff

B1 (thiamine) deficiency

Ophthalmoplegia + ataxia + confabulation
Memory loss

Dorsal medial nucleus of thalamus & mamillary body damage

63

Wet Beri-Beri

High output cardiac failure (dilated cardio myopathy), edema

64

Dry Beri-Beri

Polyneuritis, symmetrical muscle wasting

65

Vitamin B2

Riboflavin

Cheilosis
Corneal vascularization

66

Vitamin B3

Niacin

NAD derived from B3 (B3 = 3ATP)
From tryptophan & requires B6

3 D's of B3:
1. Diarrhea
2. Dermatitis
3. Dementia

Tx hyperlipidemia --> FLUSHING

67

Vitamine B5

Pantothenate (5 = "pent")

Component of CoA & FA synthesis

Deficiency: dermatitis, enteritis, alopecia, adrenal insufficiency

68

Vitamin B6

Pyridoxine

Impaired Hb synthesis + Fe excess --> Sideroblastic anemia
Convulsions
Hyper-irritability
Peripheral neuropathy

69

Vitamin B12

Cobalamin

Co-factor for homocysteine methytransferase
Animal products + microorganisms
Large reserve in liver

Deficiency causes:
1. spure
2. D. latum
3. pernicious anemia
4. No terminal ileum (Crohn's)

Dx etiology = Schilling test

Sx:
Macrocytic, megaloblastic anemia (MCV >100)
Hypersegmented PMNs
Subacute combined degeneration

70

Folic Acid

--> THF (co-factor w/ B12 in methyl transfer)
DNA & RNA synthesis
Foliage
Small reserves

Deficiency causes:
1. Phenytoin, sulfas, MTX

Sx
Macrocytic, megaloblastic anemia (MCV >100)
Hypersegmented PMNs
Most common vitamin deficiency
Alcoholism & pregnancy

71

Biotin deficiency

excess egg whites - AVIDIN binds biotin

72

Vitamin C

Ascorbic acid

Oxidized Fe3 --> Fe2 = Iron abs
Hydroxylation of proline & lysine --> collagen synthesis

Deficiency causes:
1. Scurvy - collagen synthesis defect

Sx:
Swollen gums, bruising, hemarthrosis, anemia, poor wound healing

Excess:
N/V/D, iron toxicity, fatigue

73

Vitamin D

D2 = ergo = plants
D3 = cholecalciferol = milk, sun
25-OH = storage
1,25-OH = active

Function = intestinal Ca+ & Phos abs, bone mineralization

Deficiency:
Rickets
Osteomalacia
INADEQUATE AMOUNT IN BREAST MILK

Excess:
Loss of appetite, stupor
Seen in sarcoid

74

Vitamin E

Protects erythrocytes from ROS

Deficiency:
Hemolytic anemia
Muscle weakness
Post column, spinocerebellar demyelination

75

Vitamin K

synthesized by intestinal flora

Required for clotting factor synthesis - II, VII, IX, X

Deficiency:
Inc PT & aPTT
Normal bleeding time
Neonates = sterile intestines = can't make
NOT in breast milk = injection to prevent hemorrhage
After prolonged antibiotics

76

Zinc

Essential for many enzymes
Zinc fingers - transcription factor motif

Deficiency:
Delayed wound healing
Hypogonadism
Ded adult hair
Dysgeusia
ANOSMIA

77

Fomepizole

Inhibits alcohol dehydrogenase (0-order kinetics)

***antidote for methanol or ethylene glycol OD***

78

Disulfram (antabuse)

Inhibits acetaldehyde dehydrogenase --> acedalhedhye accumulates = hangover

79

Kwashiorkor

Protein malnutrition

Edema
Fatty liver change d/t dec APO synthesis

80

Marasmus

ENERGY malnutrition

Tissue & muscle wasting
Loss of subq fat

81

Electron transport inhibitors

Rotenone
CN-
Antimycin A
CO

82

ATPsynthase inhibitors

Oligomycin

83

Uncoupling agents

Inc membrane permeability --> dec H+ gradient
Produces heat

2,4-DNP
Aspirin

84

G6PD Deficiency

NADPH required to keep glutathione reduced
Glutathione detoxifies ROA & peroxides
Dec NADPH --> HEMOLYTIC ANEMIA

Most common human enzyme deficiency
XR
Common among Blacks
Inc malarial resistance

*Heinz bodies*
*Bite cells*

85

Essential fructosuria

Defect in fructokinase
AR
Benign, Asx condition

Fructose appears in urine

86

Fructose Intolerance

AR deficiency of ALDOLASE B

Fruc-1-P accumulates --> less phis --> inhibits glycogenolysis & gluconeogenesis

Sx:
Hypoglycemia
Jaundice
Cirrhosis
Vomiting

87

Galactokinase deficiency

AR deficiency in galactokinase

Galactitol accumulates

Sx:
Galactose in urine
*Infantile cataracts*
Failure to tract objects or develop smile

88

Classic galactosemia

AR absence of Galactose-1-P Uridyltransferase

Sx:
FTT
Jaundice
Hepatomegaly
*Infantile cataracts*

Tx = exclude galactose & lactose

89

Lactase deficiency

Age or hereditary loss (Blacks & Asians)
Loss of brush border enzyme

90

Oxidizing agents for G6PD deficiency

Oxidizing agents:
1. Fava beans
2. Sulfonamides
3. Primaquine
4. Anti-TB

91

Sorbitol dehydrogenase deficiency

Glucose --> sorbitol (aldose reductase)
Sorbitol --> Fructose (sorbitol dehydrogenase)

Sorbitol accumulates
- cataracts
- retinopathy
- peripheral neuropathy

92

Acidic A.A.

Asp
Glu

Negatively charged at body pH

93

Basic A.A.

Arg
Lys
His

Arg & His = growth
Arg & Lys = histones
His = no charge at body pH

94

Rate-limiting step in Urea Cycle

NH4 --> Carbamoyl Phos

Carbamoyl phosphate synthetase I

95

Cori cycle

Lactate produced from pyruvate in anaerobic conditions instead of ATP

Transported to liver to undergo gluconeogenesis back to glucose

96

Hyperammonemia

Excess NH4+ --> depletes alpha-KG --> inhibits TCA

Tx:
Limit protein
Lactulose acidifies GI & traps NH4+ for excretion

97

Ammonia intoxication

tremor
slurring
somnolence
vomiting
cerebral edema
blurred vision

98

OTC deficiency

XR

Can't eliminate ammonia (urea cycle)

Excess carbamoyl phos --> orotic acid

99

*Musty odor*
MR
Growth retardation
Seizures
Fair skin
Eczema

PKU
- AR Dec Phenylalanine hydroxylase
- Tyrosine become essential
- Excess phenylketones in urine

100

Dark CT
Brown sclera
*Urine turns black on exposure to air*

Alkaptonuria
- Congenital deficiency of homogentisic acid
(no degradation of Tyr --> fumarate)

101

Albinism

Lack of:
1. Tyrosinase (no melanin from Tyr)
2. Defective tyrosine transporters (dec Tyr = dec melanin)

102

Lens subluxation
atherosclerosis
MR
Tall w/ kyphosis

Homocystinuria
1. Cystathione synthase deficiency
- Inc cysteine, B12, Folate

2. Dec affinity of cystathione synthase
- Inc B6

3. Homocysteine methyltransferase deficiency
- B12

103

Cystinuria

AR
Defect in PCT Cysteine, ornithine, lys, arg transporter

Can --> cystine kidney stones (staghorn calculi)
Tx: = acetazolamide to alkalinize urine

104

Maple syrup urine disease

Blocked degradation of BRANCHED A.A.
Ile
Leu
Val
"I Love Vermont maple syrup"

Severe CNS, MR, death

105

Hartnup disease

AR
Defective NEUTRAL A.A. transporter
Renal or intestinal epithelial cells

Tryptophan excretion
Dec abs in gut
PELLAGRA

106

Von Gierke's Disease (Type I glycogen)

Deficiency = Glu-6-Phosphatase

Severe fasting hypoglycemia
Hepatomegaly (glycogen storage)
Inc blod lactate

107

Pompe's Disease (Type II glycogen)

Deficiency = Lysosomal alpha-1,4-glucosidase

Pompe-Pump
Cardiomegaly

108

Cori's Disease (Type II glycogen)

Deficiency = Debranching alpha-1,6-glucosidase

Milder type I w/ NORMAL lactate

109

McArdle's Disease (type IV glycogen)

Deficiency = skeletal muscle glycogen phosphorylase

McArdle-Muscle
Painful muscle cramps w/ exercise
Myoglobinuria
High glycogen in muscle that can't be broken-down

110

Fabry's

Deficiency = alpha-galactosidase
Accumulate = Ceramide trihexose

ONLY non AR lysosomal storage disorder = XR

Sx:
Peripheral neuropathy
Angiokeratomas

111

Aseptic necrosis of femur, crumpled MOs, hepatosplenomegaly

Gaucher's
- Deficiency = Glucocerebrosidase
- Accumulate = Glucocerebroside

****Gaucher's cells = crumpled tissue paper MO***

112

Cherry-red spot on the macula + Hepatosplenomegaly (vs. Tay-Sachs)
Foam Cells

Niemann-Pick
- Deficiency = Sphingomyelinase
- Accumulate = Sphingomyelin
"No man Picks his nose with his Sphinger"

113

Cherry-red sopt on the macula W/O hepatosplenomegaly
Lysosomes w/ onion skin

Tay-SaX
- Deficiency = HeXosamidase A
- Accumulate = GM2 ganglioside
- hepatosplenomegaly (vs. Niemann-Pick)

114

Peripheral neuropathy
Optic atrophy
Globoid cells

Krabbe's Disease
- Deficiency = B-Klactocerebrosidase
- Accumulate = Kalactocerebroside

115

Central + peripheral demyelination w/ ataxia
Dementia

Metachromatic Leukodystrophy
- Deficiency = Arylsulfatase A
- Accumulates = Cerebroside sulfate

116

Gargoylism
Corneal clouding
Airway obstruction
Corneal clouding

Hurler's
- Deficiency = alpha-L-iduronidase
- Accumulate = Heparan sulfate, dermatan sulfate
- Corneal clouding (vs. Hunter's)

117

Hunter's Syndrome

Deficiency = Iduronate sulfatase
Accumulate = Heparan sulfate, dermatan sulfate

Sx:
Mild Hurler's + AGGRESSIVE BEHAVIOR
NO corneal clouding (vs. Hurler's)

118

Abetalipoproteinemia

Hereditary inability to synthesize lipoproteins
- deficiencies in apoB-100 & apoB-48

Accumulation in enterocytes - can't export lipids as chylomicrons

Sx:
FTT
Steatorrhea
Night blindness
Acanthocytosis
Ataxia

119

Hypertriglyceridemia

Inc VLDL
Inc blood TGs

Hepatic OVERPRODUCTION of VLDL --> pancreatitis

120

Familial Hypercholesterolinemia

Inc LDL
Inc blood cholesterol

AD dec/absent LDL receptors
--> accelerated atherosclerosis
--> tendon xanthomas (achilles)
--> corneal arcus

121

Hyperchylomicronemia

Inc Chylomicrons
Inc blood cholesterol & TGs

LPL deficiency OR
altered aopC-II

Sx:
Pancreatitis
Hepatosplenomegaly
Eruptive/pruritic xanthomas (NO risk for atherosclerosis)

122

DNA Methylation

Mute transcription

123

DNA Methylation

Mute transcription

124

Histone Acetylation

Euchromatin = active

125

Histone Acetylation

Euchromatin = active