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Flashcards in BioChem Deck (149):
1

Tuberous Sclerosis
What kind of inheritance?
Manifestations?

Autosomal Dominant w/ incomplete penetrance
Harmatomas of CNS and Retina, Adenoma Sebaceum (cutaneous angiofibroma), Mitral Reg, Ash-Leaf Spots on skin, Cardiac Rhabdomyomas, Mental Retardation, Renal Angiomyolipomas and Renal Cysts, Seizures, Increased incidence of astrocytomas

2

Histones?
Charge
Amino Acids
What do they form?
What ties it together?

Positively charged
Lysine and Arginine
Octamer tied together by H1

3

DNA methylation
Which Nucleotides
When in cell cycle?
Function
What organisms

C and A
Template strand is methylated during DNA replication which allows mismatch repair enzymes to distinguish between old and new strands
Prokaryotes

4

What does Histone Methylation do?

Inactivates DNA

5

What does Histone Acetylation do?

Relaxes DNA coiling allowing for transcription

6

Purines
Names
Rings
What is it made from?

"PURe As Gold"
Adenine, Guanine
2 rings
Glycine, Aspartate, Glutamine

7

Pyrimidines
Names

"CUT the PY"
Cytosine, Uracil, Thymine

8

Molecular group on Guanine

Ketone

9

Molecular group on Thymine

MeTHYl

10

How is Uracil made?

Cytosine gets Deaminated

11

RNA Nucleotides?

G-C, A-U

12

DNA Nucleotides

G-C, A-T

13

Which nucleotide bond is strongest

G-C has 3 hydrogen bonds

14

How is DNA melting point affected

↑ GC content --> ↑ melting temperature

15

Nucleoside

Base + Ribose

16

Nucleotide

Base + Ribose + Phosphate linked by 3'5' phosphodiester bond

17

What makes up Pyrimidines

Aspartate and Carbamoyl Phosphate

18

Basic schematic of de novo purine synthesis

Start with sugar + phosphate (PRPP)
Then add base

19

Basic schematic of de novo pyrimidine synthesis

Make temporary base (orotic acid)
Add sugar + phosphate (PRPP)
Modify base

20

Purine synthesis pathway

Ribose 5-P --> PRPP ->->-> IMP --> AMP and GMP

21

Inhibition of de novo purine synthesis

6-mercaptopurine blocks de novo purine synthesis

22

Production of deoxyribonucleotides

Ribonucleotide reductase converts ribonucleotides into deoxyribonucleotides

23

CTP synthesis

Ribose 5-P --> PRPP
PRPP + Orotic Acid --> UMP --> UDP --> CTP

24

dTMP synthesis

Ribose 5-P --> PRPP
PRPP + Orotic Acid --> UMP --> UDP --> [Ribonucleotide reductase] --> dUDP --> dUMP --> [Thymidylate Synthase] --> dTMP

25

What pathways is Carbamoyl Phosphate involved with?

de novo pyrimidine synthesis and urea cycle

26

Ornithine transcarbamoylase deficiency
What is it?
Findings

OTC is a key enzyme in the urea cycle
Deficiency leads to accumulation of carbamoyl phosphate which is then converted into orotic acid
↑ Orotic acid with hyperammonemia

27

What inhibits Ribonucleotide reductase

Hydroxy Urea

28

What inhibits Thymidylate Synthase?

5-Fluorouracil

29

What inhibits human Dihydrofolate reductase
Net result?

Methotrexate
↓ dTMP

30

What inhibits bacterial Dihydrofolate reductase
Net result?

Trimethoprim
↓ dTMP

31

THF and dTMP synthesis

THF --> N5N10 methylene THF --> [Thymidylate Synthase] --> DHF --> [Dihydrofolate reductase] --> THF

32

Orotic Aciduria
What is it?
Pathway involved?
Where is the defect?
Genetics
Findings
Treatment

Inability to convert orotic acid to UMP
de novo pyrimidine synthesis pathway
UMP synthase
Autosomal Recessive
↑ orotic acid in urine, Megaloblastic anemia (does not improve with B12 or folic acid), Failure to thrive, No hyperammonemia
Oral uridine administration

33

Adenine salvage pathway

Adenine + PRPP --> [APRT] --> AMP
AMP can become Nucleic acids, Adenosine, or IMP

34

Fate of Adenosine in salvage pathway

Adenosine can become AMP or Adenosine deaminase (ADA) can turn it into Inosine

35

Fate of IMP in purine salvage pathway

Hypoxanthine + PRPP --> [HGPRT] --> IMP
IMP can become inosine, AMP, or GMP

36

Fate of Inosine in Purine salvage pathway

Adenosine --> Inosine
Inosine --> Hypoxanthine

37

Fate of Hypoxanthine in Purine salvage pathway

Hypoxanthine can become IMP, Inosine, or Xanthine

38

Fate of Guanine in Purine salvage pathway

Guanine +PRPP --> [HGPRT] --> GMP
Guanine --> Guanosine
Guanine --> Xanthine

39

Fate of Guanosine in Purine salvage pathway

GMP --> Guanosine
Guanine ↔ Guanosine

40

Fate of GMP in Purine salvage pathway

GMP can be come Nucleic Acids, IMP or Guanosine

41

Adenosine Deaminase Deficiency
PathoPhys
Genetics
What does it lead to
Treatment

Excess ATP and dATP leads to an imbalance in nucleotide pool via feedback inhibition of ribonucleotide reductase thus preventing DNA synthesis thus ↓ Lymphocyte count
Autosomal recessive
SCID
1st disease to be treated by experimental human gene therapy

42

Lesch-Nyhan Syndrome
Deficiency
Metabolic result
Genetics
Findings

"He's Got Purine Recovery Trouble"
HGPRT mutation which converts hypxanthine into IMP and Guanine into GMP
Excessive uric acid production and de novo purine synthesis
X linked recessive
Retardation, Self-Mutilation, Aggression, Hyperuricemia, Gout, Choreoathetosis

43

Genetic Code Features
Unambiguous
Degenerate
Commaless
Universal

Each codon = 1 AA
Most AA are coded by multiple codons except for Methionine (AUG) and Tryptophan (UGG)
Nonoverlapping: fixed starting point at a continuous sequence of bases except in some viruses
Conserved throughout evolution except in human mitochondria

44

Silent mutation

Same AA usually at 3rd position of condon (tRNA wobble)

45

Missense mutation

Changed AA to a similar AA

46

Nonsense mutation

Early stop codon

47

Frameshift

Misreading of all downstream nucleotides resulting in truncated, nonfunctional protein

48

DNA topoisomerases
Function
What inhibits it

Creates a nick in the helix to relieve supercoil created during replication
Fluoroquinolones inhibit prokaryotic topoisomerase II

49

DNA pol III
What organisms?
Direction of synthesis
Other functions?

Prokaryotic only
5' --> 3'
Proofreads 3' to 5'

50

DNA pol I
What organisms
Function
Functions with directions

Prokaryotic only
Degrades RNA primer and replaces it with DNA
Synthesis 5' --> 3'
Proofreading 3' --> 5'
Exonuclease 5' --> 3'

51

DNA ligase

Catalyzes the formation of phosphodiesterase bonds within strand of dsDNA. Joins Okazaki fragments

52

Telomerase

Adds DNA to 3' end of chromosome to avoid loss of genetic material with every duplication

53

Nucleotide Excision repair
Process
What kind of lesions does it repair
Disease involving this pathway

Specific endonucleases release the oligonucleotide-containing damaged bases. Then DNA pol and Ligase fill and reseal the gap
Repairs bulky helix distorting lesions
Xeroderma pigmentosum: Prevents repair of pyrimidine dimers because of UV light

54

Base Excision repair
Process
What kind of lesions does it repair?

Specific glycosylases recognize and remove damaged bases. Apurinic/Apyrimidinic endonucleases cut DNA at both sites. Empty sugar is removed. Gap is filled in and resealed
Important in reapir of spontaneous/toxic deamination

55

Mismatch Repair
Process
Disease

Newly synthesized strand is recognized, mismatched nucleotides are removed and gap is filled and resealed
Mutated in Hereditary NonPolyposis Colorectal Cancer (HNPCC)

56

Nonhomologous end joining
Process
Requirements
Disease

Brings together 2 ends of DNA fragments to repair double stranded breaks
No requirement for homology
Mutated in ataxia telangiectasia

57

Direction of DNA and RNA synthesis?
Energy source?

5' --> 3'
5' end of dNTP

58

In which direction is mRNA read?

5' --> 3'

59

Direction of Protein Synthesis

N to C

60

Most abundant type of RNA

rRNA

61

Ways to remember types of RNA?

"Rampant, Massive, Tiny"

62

Eukaryotic start codon

"AUG inAUGurates protein synthesis"
AUG (rarely GUG) which codes for Methionine

63

Prokaryotic start codon

AUG which codes for formylmethionine

64

mRNA stop codons

UGA: U Go Away
UAA: U Are Away
UAG: U Are Gone

65

Promoter code

TATA Box
TATAAT and CAAT

66

Start of transcription numbering

+1

67

Termination signal

AATAAA

68

Eukaryotic RNA pol
I, II, III
Functions

Numbered in order that they are used in protein synthesis
I: rRNA
II: mRNA - can open DNA at promoter site
III: tRNA
No proofreading function but can initate chains

69

Prokaryotic RNA pol

1 RNA pol (multisubunit complex) makes all 3 kinds of RNA

70

What inhibits RNA pol II
What does it lead to

α-amanitin (from mushroom)
Hepatotoxicity if ingested

71

RNA processing in eukaryotes
What is initial transcript called?
What is it called if destined for transcription?
Where does processing occur?

Heterogenous nuclear RNA
pre-mRNA
Processing occurs in the nucleus

72

RNA processing in eukaryotes

Capping on 5' end with 7-methylguanosine
Polyadenylation an 3' end
Splicing out of introns

73

What is required for RNA to be transported out of the nucleus

Only processed RNA can be transported out of the nucleus

74

Polyadenylation
What enzyme does it?
Template?
Signal

Poly-A polymerase
Does not require a template
AAUAAA

75

Steps of Splicing pre-mRNA

Primary transcript combines with snRNPs (small nuclear ribonucleoproteins) and other proteins to form a spliceosome
Lariat shaped (looped) intermediate is generated
Lariat is released to remove intron precisely and join 2 exons

76

Disease involving snRNPs

Lupus: autoAbs to spliceosomal snRNPs

77

tRNA
Length
Secondary structure
What is on end?
Which end binds AAs

75-90 NTs
Cloverleaf form
On 3' end is 5' CCA 3' along with a high percentage of chemically modified bases
3' is bound to AA

78

tRNA Charging
Enzyme
Proofreading
Energy

Aminoacyl-tRNA synthetase
Scrutinizes AA before and after it binds tRNA
If incorrect, bond is hydrolyzed
AA-tRNA bond has energy for formation of peptide bond

79

Tetracyclines

Bind 30S subunit and prevents attachment of aminoacyl tRNA to A site

80

Eukaryote Ribosomes

Even #s
40S and 60S

81

PrOkaryote Ribosomes

Odd #s
30S and 50S

82

Protein synthesis initiation

Activated by GTP hydrolysis
Initiation Factors help assemble 40S ribsomal subunit with the initiator tRNA and are then released

83

Protein synthesis Elongation

"Going APE"
1. Aminoacyl-tRNA binds A site (except initiator methionine)
2. rRNA catalyzes peptide bond formation transferring polypeptide into A site
3. Peptidyl tRNA moved into P site and empty tRNA moves to E site

84

Protein synthesis Termination

Stop codon recognized by release factors and complete protein is released from ribosome

85

Aminoglycosides

Bind 30S and inhibit formation of initiation complex and cause misreading of mRNA

86

Chloramphenicol

Binds 50S and inhibits peptidyl transferase

87

Macrolides

Bind 50S and prevent release of uncharged tRNA after it has donated its AA

88

Process of Proteasomal degradation

Attachment of Ubiquitin tags them for breakdown

89

Stages of cell cycle

G1 --> [Rb, p53] --> S --> G2 --> Mitosis

90

Interphase

G1, S, and G2

91

Stages of mitosis

Prophase, Metaphase, Anaphase, Telophase

92

Regulation of Cell Cycle
CDKs
Cylcins
Cyclin-CDK complexes

CDKs are constitutively present and inactive
Cyclins are regulatory and are produced in a phase specific manner
Cyclin-CKD complexes activate and the inactivate for cell cycle to progress

93

Tumor Suppressors
Names
Function

p53 and Hypophosphorylated Rb
Normally inhibit G1 to S progression

94

Permanent cell type
Phase
What do they form
Examples

Remain in G0
Regenerate from stem cells
Neurons, Skeletal muscle, Cardiac muscle, RBCs

95

Stable cell types
Name
Phase
Examples

Quiescent
Enter G1 from G0 when stimulated
Hepatocytes and Lymphocytes

96

Labile cells
Phase
Examples

Never go to G0. Divide rapidly with a short G1
Bone marrow, Gut epithelium, Skin, Hair follicles, Germ cells

97

Rough Endoplasmic Reticulum
What kind of proteins are synthesized here?
Protein modifications

Site of synthesis of secretory (exported) proteins
N linked oligosaccharide addition to many proteins

98

Nissl Bodies

RER in neurons
Synthesizes ChAT (choline acetyltransferase) to make ACh and peptide NTs

99

What do free ribosomes produce

Cytosolic and organellar proteins

100

Which kind of cells are rich in RER?

Mucus-secreting goblet cells of SI and Ab secreting plasma cells

101

Smooth Endoplasmic Reticulum
What is synthesized here?
Which cells are rich in it?

Site of steroid synthesis and detoxification of drugs and poisons
Liver hepatocytes and steroid hormone-producing cells of adrenal cortex are rich in SER

102

Modifications that take place in Golgi?

Modifies N-oligosaccharides on Asparagine
Adds O-oligosaccharides on Serine and Threonine

103

What directs proteins to lysosomes

Mannose-6-Phosphate added in lysosomes

104

I cell disease
Genetics
PathoPhys
Presentation

Inherited lysosomal storage disorder
Failure of addition of mannose-6-phosphate in golgi means enzyme are directed outside of cell instead of lysosomes
Coarse facial hair, Clouded corneas, Restricted joint movement, High plasma levels of lysosomal enzymes. Often fatal in childhood

105

Vesicle trafficking proteins
COPI
COPII
Clathrin

COPI: Retrograde (Golgi --> Golgi, Golgi --> ER)
COPII: Anterograde (Golgi --> Golgi, ER --> Golgi)
Clathrin: trans-Golgi --> lysosomes, Plasma membrane --> Endosomes (receptor mediated endocytosis)

106

Peroxisomes

Membrane enclosed organelle involved in catabolism of very long fatty acids and AA

107

Proteasomes

Barrel shaped protein complex that degrades damaged or unnecessary proteins tagged for destruction by ubiquitin

108

Microtubules
Composition
What is each dimer bound to?
What cellular structures does it make up? What functions are they involved with?
How does it grow and collapse?

α and β subunits
Each dimer has 2 GTPs bound to it
Flagella, Cilia, Mitotic spindles, Centrioles
Slow Axonal Transport and Cell Movement
Grows slowly, collapses quickly
Involved in slow axoplasmic transport in neurons

109

Molecular motor proteins

Dynein: retrograde in MTs (+ --> -)
Kinesin: anterograde in MTs (- --> +)

110

Drugs that act on MTs

Mebendazole/Thiabendazole: antihelminthic (prevents polymerization)
Griseofulvin: antifungal (prevents polymerization)
Vincristine/Vinblastine: anticancer (prevents polymerization)
Paclitaxel: anti-breast cancer (Stabilizes MTs)
Colchicine: antigout (prevents polymerization)

111

Chediak-Higashi Syndrome
Where is the mutation?
PathoPhys
Presentation

Mutation in lysosomal trafficking regulator gene (LYST)
LYST required for MT dependent sorting of endosomal proteins into late multivesicular endosomes
Recurrent pyogenic infections, Partial albinism, Peripheral neuropathy

112

Cilia
Structure
Motor proteins
Disease

9+2 arrangement of MTs. 9 doublets of MTs + 2 individual MT in middle
Dynein links peripheral 9 doublets
Kartagener's Syndrome

113

Kartagener's Syndrome
PathoPhys
Presentation
Associated with what developmental defect

Immotile cilia due to dynein arm defect
Male infertility, ↓ female fertility, Bronchiectasis, Recurrent sinusitis
Associated with sinus inversus

114

Actin and Myosin functions

Microvilli, Muscle contraction, Cytokinesis, Adherens junctions

115

Intermediate filament names and stains

Vimentin: Connective tissue
Desmin: Muscle
Cytokeratin: Epithelial cells
Glial Fibrillary Acid Protein (GFAP): NeuroGlia
Neurofilaments: Neurons

116

Plasma Membrane composition

Cholesterol, Phospholipids, Sphingolipids, Glycolipids, and Proteins

117

When is Na/K APTase phosphorylated

When open to extracellular side

118

Ouabain

Inhibits Na/K ATPase by binding to K site

119

Cardiac Glycosides
Names
MoA

Digoxin and Digitoxin
Inhibits Na/K ATPase leading indirectly to increased Ca --> increased contractility

120

Most abundant protein in the human body

Collagen

121

Type I collagen
Frequency
Where is it present?
Disease

Most common collagen (90%)
Bone, Skin, Tendon, Dentin, Fascia, Cornea, Late Wound Repair
Defective in Osteogenesis Imperfecta

122

Where is type II collagen

Cartilage (including hyaline, Vitreous body, Nucleus pulposus

123

Type III collagen
Where is it present
Disease

Reticulin - skin, blood vessels, uterus, fetal tissue, granulation tissue
Ehlers-Danlos (vascular type)

124

Type IV collagen
Where is it present
Disease

Basement membrane (basal lamina)
Alport Syndrome

125

Collagen mnemonic

"Be (So Totally) Cool, Read Books"
I: Bone, Skin, Tendon
II: Cartilage
III: Reticulin
IV: Basement Membrane

126

Collagen synthesis inside the fibroblasts

1. RER: translation of α chains (preprocollagen)
2. ER: Hydroxylation of specific proline and lysine residues (requires VitC)
3. ER: Glycosylation of pro-α-chain hydroxylysine residues
4. Formation of procollagen via hydrogen and disulfide bonds (triple helix of 3 α chains)
5. Exocytosis

127

Osteogenesis imperfecta
Type of collagen
PathoPhys
Genetics
Presentation

Type I collagen defect
Problem forming triple helix of collagen α chains
Genetic bone disorder caused by a variety of gene defects but most common form is Autosomal Dominant
Brittle bones (multiple fractures with minimal trauma), Blue sclerae (translucent connective tissue over choroidal veins), Hearing loss (abnormal middle ear bones), Dental imperfections (lack of dentin)

128

Collagen synthesis outside of fibroblasts

1. Cleavage of disulfide rich terminal regions of procollagen forming insoluble tropocollagen
2. Reinforcement of many staggered tropocollagen molecules by covalent lysine-hydroxylysine cross linkage (by Cu2+ containing lysyl oxidase)

129

Ehlers-Danlos
Type of collagen involved?
PathoPhys
Presentation
# of types
Inheritance
Associations
Don't confuse w/

Type III or V defect
Problems with cross linking by Cu2+ containing lysyl oxidase
Hyperextensible skin, Easy bleeding and bruising, Hypermobile joints
6 types
Can be AD or AR
Joint dislocation, berry aneurysm, organ rupture
Marfan's

130

VitC deficiency

Scurvy

131

Alport Syndrome
Type of collagen involved
Inheritance
Presentation

Type IV
Variety of genetic defects but most commonly X linked recessive
Progressive hereditary nephritis, deafness, and ocular disturbances

132

Elastin
What is it? Where is it?
What is it made of?
Scaffolding?
Where does cross-linking take place?
What does cross-linking accomplish?
What breaks it down?

Stretchy protein within skin, lungs, large arteries, elastic ligaments, vocal cords, ligamenta flava (connect verbetrae --> relaxed and stretched conformations)
Rich in proline and glycine (nonhydroxylated forms)
Tropoelastin with fibrillin scaffolding
Cross-linking takes place extracellularly and gives elastin its elastic properties
Broken down by elastase (which is normally inhibited by α1 antitrypsin)

133

What causes wrinkles of aging?

Reduced collagen and elastin production

134

Southern Blot

DNA electrophoresed, transfered to filter, denatured, labeled with probe

135

Blots mnemonic

SNoW DRoP
Southern - DNA
Northern - RNA
Western - Protein

136

Northern Blot

RNA used

137

Western Blot

Protein used

138

Southwestern Blot

Identifies DNA-Binding Proteins using labeled oligonucleotide probes

139

Microarrays

Nucleic acid sequences arranged on a grid and samples hybridize to the chip
Can detect SNPs

140

Enzyme-Linked Immunosorbent Assay
Indirect
Direct

Indirect: Test antigen to see if specific Ab is in pt's blood. Secondary Ab coupled to a color generating enzyme is added to detect 1st Ab
Direct: Test Ab coupled to a color generating enzyme to see if a specific antigen is present in pt's blood

141

Fluorescence in situ Hybridization (FISH)

Fluorescent DNA or RNA probes bind to specific gene sites on chromosomes.
Used for specific localization of genes and direct visualization of anomalies at molecular level (when deletion is too small to be karyotyped)

142

Karyotyping
What is it?
What tissue can it be gotten from?
Uses

Metaphase chromosomes are stained, ordered, and numbered according to morphology, size, arm-length ratio and banding pattern
Blood, Bone marrow, Amniotic fluid, Placental tissue
Used to diagnose chromosomal imbalances

143

16S ribosome
Where is it?
Function

30S ribosome
Binds complimentary mRNA to initiate translation - Shine Delgarno Sequence

144

Lac Operon when Glucose is added

Glucose --/ AC, leading to a decrease in cAMP
When glucose is not present, cAMP is high and cAMP-CAP complex promotes transcription

145

Septic Shock Acidosis
What kind of acidosis
Impairment

Lactic Acidosis with an Anion Gap
Tissue Hypoxia --> Anaerobic Respiration and impairment of OxPhos

146

How does TNF alpha affect glucose uptake

TNF --> Serine phosphorylation which decreases the activity of the Insulin RTK

147

Floppy baby with jaundice, enlarged tongue, hypotonia, umbilical hernia, hoarse cry, constipation...
What do they have
What are they at risk for?

Hypothyroidism
Congenital heart defects

148

How does Radiation kill tumor cells?

dsDNA breaks and free radicals

149

Rasburicase
Mechanism
Use

Metabolizes Uric Acid into Allantoin which is more soluble
Tumor Lysis Syndrome