Usmle - Biochem 1/4

Front 1

(1) What are the proportions of lipid-subtypes in the cell membrane?

(2) How does cholesterol effect the structure of a lipid membrane?

Back 1

(1)
50% phospholipids

50% cholesterol

Traces of others

Hint 1

(2)
Cholesterol stiffens and weakens the bilipid membrane because it interferes with the fluid interaction of phospholipids.

Front 2

Location of Vimentin

Back 2

Intermediate filament found in connective tissue

Front 3

Location of Desmin

Back 3

Intermediate filament found in muscle

Front 4

Location of Cytokeratin

Back 4

Intermediate filament found in epithelial cells

Front 5

Location of GFAP

Back 5

Intermediate filament found in found in Neuroglia

Front 6

Location of Neurofilaments

Back 6

Intermediate filament found in neurons.

Front 7

How does knowing the 5 intermediate filaments help us?

Back 7

Because they're very large and abundant cytoskeletal structures, a stain specific for one of them will light up the tissue it lives in.

Front 8

Ouabain
Mech:

Back 8

This toxin is found in leaves and bark in Africa and was used to poison arrow and spear-tips.

It blocks the K+ side of Na/K ATPase.

Front 9

Cardiac glycosides
Mech:

Back 9

Directly inhibit Na/K ATPase (slightly), decreasing the cells ability to pump out Ca2+.

Result: increased intracellular Ca2+ = increased cardiac contractility!

Front 10

Where are types II and III collagen found?

Back 10

Type II collagen: found in cartilage.

Type III collagen: found in blood vessels, lymph nodes, dermis, and early wound healing. AKA reticulin

Front 11

Ehler Danlos?
Path & Presentation:

Back 11

Path: Type III collagen is defective d/t alpha chain mutation.

Hint 11

Presentation: joint hypermobility, hyperelastic skin, heart valve issues

Front 12

Types of Collagen disorders:

Back 12

Type I: Osteogenesis imperfecta, scurvy

Type III: Ehler Danlos

Type IV: Alport's (defective) & Goodpastures (auto-antigenic)

Front 13

Describe Collagen Structure:

Back 13

Triple helix made of Gly-X-Y repeats!

X and Y can be proline, hydroxyproline, or hydroxylysine!

The Glycine residues line up axially, stabilizing the structure by their hydrophobic interactions.

Front 14

Steps of Collagen Synthesis:

Back 14

(1) Intracellular steps:
1. Translation of Gly-X-Y polypeptide.
[preprocollagen]

2. Hydroxylation of lysin and proline residues
(requires vitamin C)

3. Glycosylation of hydroxylysine residues

Hint 14

(2) Extracellular steps:

4. Proteolytic processing: cleavage of terminal regions of procollagen
[Tropocollagen, the basic monomer]

5. Tropocollagen strands link to eachother via lysine-hydroxylysine crosslinkages for enhanced strength.
[Collagen fibril]

Front 15

Steps of Collagen Synthesis:

Back 15

(1) Intracellular steps:
1. Translation of Gly-X-Y polypeptide.
[preprocollagen]

2. Hydroxylation of lysin and proline residues
(requires vitamin C)

3. Glycosylation of hydroxylysine residues

Hint 15

(2) Extracellular steps:

4. Proteolytic processing: cleavage of terminal regions of procollagen
[Tropocollagen, the basic monomer]

5. Tropocollagen strands link to eachother via lysine-hydroxylysine crosslinkages for enhanced strength.
[Collagen fibril]

Front 16

How does intracellular collagen differ from extracellular collagen? Why must we finish making this stuff outside the cells?

Back 16

As pro- and preprocollagen, the molecule is still soluble.

Once the hydrophilic end segments are cleaved in the RER lumen, the molecule becomes insoluble, and would be lethal to cells.

Front 17

What are the most common and most deadly forms of osteogenesis imperfecta? How do they differ?

Back 17

Osteogenesis Imperfecta Type I:
Mildest form
Autosomal dominant

Osteogenesis Imperfecta Type II:
autosomal recessive
Lethal, perinatally

Front 18

Steps of PCR:

Back 18

1. Denaturation:
Add lots of mRNA primers, dNTPs, and heat-stabile DNA Polymerase from geyser bacterium to your sample, and heat to denature it.

2. Reanneal: cool enough for RNA primers to anneal, and for special DNA-P to do its work.

Repeat, repeat, repeat

Hint 18

Concept: we use RNA primers that we know to be flanking the gene we want to amplify.

After several cycles, we'll have tons of DNA from that gene only.

Front 19

How do we visualize our PCR results?

Back 19

This lab test is visualized using gel electrophoresis on agarose gel.

Shorter pieces of DNA travel further.

We then compare the gel against a DNA ladder.

Front 20

Which Blotting Technique does what?

Back 20

SNoW
DRoP

Southern Blot: used to separate DNA

Northern Blot: used to separate RNA

Western Blot: used to separate Protein

Front 21

Materials for a Laboratory Blot:

Back 21

1. DNA/RNA/Protein is electrophoresed on agarose gel, then transferred to a filter.

2. Denaturant is applied and radiolabeled primers are added
[nucleic acid primers for Noorthern and Southern blots, and antibody primers for Western blot]

3. Read by exposing to film

Front 22

Laboratory Blot Techniques:

Back 22

1. DNA/RNA/Protein is electrophoresed on agarose gel, then transferred to a filter.

2. Denaturant is applied and radiolabeled primers are added
[nucleic acid primers for Noorthern and Southern blots, and antibody primers for Western blot]

3. Read by exposing to film

Front 23

How does microarray work?

Back 23

We immobilize thousands of DNA fragments from known genes on a chip, then add radiolabeled primers from our patient sample.

I have no idea how we get radiolabeled primers from a patients blood/CSF/urine sample, but we do.

Front 24

How do ELISA's work?

Back 24

If we're testing for the presence of an antibody in the patient's serum, add its antigen with peroxidases specially attached.

If we're testing for presence of an antigen in the patient's serum, add specific antibodies with peroxidases attached to the sample.

Either way, if the patient is sero-positive, there'll be an intense color reaction.

Front 25

Pleiotropy

Back 25

1 gene has more than 1 effect on an individual's phenotype.

i.e. PKU: it's a monogenic disorder, but causes MR, hair and skin changes, and a bunch of other seemingly unrelated problems.

Front 26

Loss of heterozygosity

Back 26

The 2nd hit of the 2-hit hypothesis.

Front 27

Dominant negative mutation
Give an example

Back 27

When a heterozygote produces 1 mutant allele that doesn't only fail to work, but also interferes with the function of the other, normal allele.

Hint 27

Example: a mutation of a Transcription factor allele in its allosteric site: allele can still bind its target, blocking out the good copy of the TF from acting!

Front 28

Lyonization

Back 28

Random X inaction in females, resulting in one normal X chromosome and one Barr body.

Perfectly normal, but it means that any mutations on the normal X chromosome will be dominant.

Front 29

Locus heterogeneity

Back 29

When mutations at two different loci cause the same phenotype.

Hint 29

Occurs in Marfan's, MEN 2B, and homocystinuria, all of which result in clinical marfan's syndrome.

Front 30

Heteroplasma

Back 30

Inheritance of both normal and mutant mitochondrial DNA (mtDNA), resulting in variable expression of mitochondrial disease.

Hint 30

Depends upon which mitochondria were inherited by the lucky germ cell!

Front 31

Achondroplasia
Etiology and biochem
Inheritance pattern

Back 31

FGFR3 (fibroblast growth factor 3) defect resulting in dwarfism, short limbs, but head and trunk are normal size.

Autosomal-dominant

Hint 31

Autosomal Dominant

Front 32

Autosomal Dominant Polycystic Kidney Disease (ADPKD)
[the adult form]
Etiology:

Back 32

Always bilateral, massive enlargement of kidneys d/t multiple large cysts.

Presents with flank pain, flank swelling, hematuria.

Hint 32

Autosomal dominant

**Associated with berry aneurisms
An infantile recessive form exists that's much worse.

Front 33

Familial Hypercholesterolemia

Back 33

Elevated LDL d/t defective or absent LDL receptor.

Presents with MI, very hi cholesterol. Homozygotes are rare and don't live long.

Hint 33

Autosomal Dominant

Front 34

Familial Adenomatous Polyposis

Back 34

Colon becomes covered in polyps. Colorectal cancer is inevitable.

APC mutation on chromosome 5.
[5 letters in polyp]

Hint 34

Autosomal Dominant

Front 35

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)
Etiology:
Pattern of Inheritance:

Back 35

Inherited disorder of blood vessels. Findings include telangiectasia, recurrent epistaxis, arteriovenous malformations.

Presents with purpura, nosebleeds, telangiectasia on tongue.

Hint 35

Autosomal Dominant

Front 36

Hereditary spherocytosis
Etiology:
Pattern of Inheritance:

Back 36

Spheroid eryhthrocytes d/t ankyrin or spectrin defect.

Presents with hemolytic anemia, increased MCHC.

This is the disorder in which the wire mesh of the normal spleen is responsible for your hemolysis.

Hint 36

Autosomal Dominant

Front 37

Marfan's Syndrome
Etiology:
Pattern of Inheritance:

Back 37

Fibrillin gene mutation resulting in connective tissue abnormalities.

Hint 37

Autosomal Dominant

Front 38

MEN
Etiology:
Pattern of Inheritance:

Back 38

Familial tumors of the endocrine glands.

Types 2A and 2B are caused by RET mutation.

Hint 38

All 3 syndromes are autosomal dominant

Front 39

Neurofibromatisis type 1
Etiology:
Pattern of Inheritance:

Back 39

Cafe Au lait spots
neural tumors
blindness

Lisch nodules are ubiquitous

Mutation on long arm of chromosome 17

Hint 39

Autosomal Dominant

Front 40

Neurofibromatosis type 2

Back 40

Bilateral acoustic schwannomas
Juvenile cataracts
NF2 on Chromosome 22

[2's disease: Type 2 on chrom. 22]

Hint 40

Autosomal dominant

Front 41

Tuberous sclerosis

Back 41

Facial lesions
Hamartomatous masses in cortex and retina
Increased incidence of astrocytomas

Hint 41

Autosomal dominant

Front 42

von Hippel-Lindau disease

Back 42

Hemangioblastomas of retina/cerebellum/medulla.

Half of these individuals also develop renal cell carcinoma.

Familial form is caused by VHL gene mutation on p arm of chromosome 3.

Hint 42

Autosomal dominant

There is also a sporadic form caused by loss of p arm of chromosome 3.

Front 43

VHL
(1) Genetics & biomolecular changes
(2) Path

Back 43

(1)
Gene located on 3p. Can be lost d/t del(3p) or mutation to the VHL gene on 3p.

VHL normally degrades the transcription factor HIF-1α, preventing it from triggering PDGF and VEG-2F expression.

Hint 43

Disease consists of medulloblastomas, hemangiomas of the retina/cerebellum/medulla.

Half of these individuals also will get renal cell carcinoma.

Bottom line: when VHL is knocked out, we'll see cancerous expansion of many small blood vessels.

Front 44

Cystic Fibrosis
Normal vs. pathological pulmonary biochem:

Back 44

Normal Lungs:

CFTR is a Cl- channel that actively secretes chloride in lungs

CFTR regulates ENaC, preventing excessive Na+ absorption by the lung epithelium.

Hint 44

Lungs in CF:

1. Cl- channel is absent or defective, so less Cl- is secreted from lung epithelium.

2. Cl- channel cannot, under these circumstances, downregulate ENaC activity, and Na+ is reabsorbed into lung epithelium too vigorously

3. H2O follows Na+ out of the airways and into the epithelium

4. Result: thick, stagnant mucous in airways that forms plugs and invites bacterial colonization.

so it can't regulate ENaC, and lots of Na+ (and therefore H2O) is reabsorbed.

Front 45

Genetics of CF & Location of Cystic Fibrosis gene

Back 45

CFTR is located on the long arm of Chromosome 7

Autosomal recessive inheritance pattern

Front 46

Complications of Cystic Fibrosis

Back 46

Lung:
1. recurrent infections by pseudomonas and staph aureaus
2. chronic bronchitis, bronchiectasis

GI: pancreatic insufficiency

Front 47

Compare CF pathophys in skin vs. lung

Back 47

In lung, CF is caused by defect in a Cl- channel that normally actively SECRETES Cl-.

In the skin, CF is caused by defect in a Cl- channel that actively REABSORBS Cl-

In both cases, pathological buildup of Cl- is mirrored by pathological buildup of Na+ and H2O, because CFTR regulates ENaC.

Front 48

Cystic fibrosis
Normal vs. pathological biochem in skin:

Back 48

Normal Skin:

1. CFTR is a Cl- transporter that actively *reabsorbs* Cl- from sweat

2. CFTR upregulates ENaC activity, and therefore Na+ reabsorption.

Hint 48

Skin in CF:

1. CFRT is absent or defective, so less Cl- is reabsorbed by the skin.

2. Cl- channel cannot regulate ENaC, so Na+ isn't reabsorbed either.

3. Lots of NaCl is lost in sweat.

Front 49

Treatment of CF

Back 49

Palliative:
1. Give N-Acetylcysteine to loosen mucous plugs
2. Give lots of electrolytes. LOTS!

Gene modification therapy is in the works but not yet ready.

Front 50

List the X-Linked Recessive disorders

Back 50

B W F G O L D H H
(Be Wise, Fool's GOLD Heeds Silly Hopes)

Bruton's aggamaglobulinemia
Wiskott-Aldrich syndrome
Fabry's Disease
G6PD Deficiency
Ocular Albinism
Lesch-Nyhan syndrome
Duchenne's muscular dystrophy
Hunter's Syndrome
Hemophilia A and B

Front 51

Duchenne's Muscular dystrophy
Genetics & Biochem

Back 51

(1)
X-linked Recessive

Deletion/frameshift mutations in Dystrophin protein

Hint 51

(2) Biochem:

Dystrophin connects Actin of cytoskeleton to sarcolemmal membrane of myocytes.

Result of deletion: force of muscle fiber contraction is not transferred to cell membrane; the cell doesn't contract, only its organelle does.

Front 52

Becker's Muscular Dystrophy
Genetics & Biochem

Back 52

(1)
X-linked recessive

Missense/nonsense Mutation (*NOT* frameshift/deletion) to dystrophin gene.

Hint 52

(2) Biochem:

Some dystrophin is made, but it's abnormal to a greater or lesser degree.

The result is a disorder that's less severe and has a later onset than in Duchenne's.

Front 53

Muscular dystrophies
Presentation & Diagnostics

Back 53

These disorders are inherited and present at anytime from childhood to early adulthood wiht progressive muscle wasting and myocyte degredation.

Histological abnormalities include:
Muscle tissue can become replaced with fat.
Muscle fibers will vary in size and diameter.

Hint 53

Diagnose via increased serum Creatinine Kinase and muscle biopsy.

Front 54

Fragile X
Path & Presentation

Back 54

X-linked defect in methylation and expression of the FMRI gene.

Results in trinucleotide expansion repeat of CGG

Hint 54

Second most common cause of MR!

X-linked, X-tra long gene, Xtra large testes, jaw, and ears!!

Front 55

List the trinucleotide repeat diseases and their repeated sequences.

Back 55

1. Fragile X: CCG
2. Friedrich's ataxia: GAA
3. Huntington's Disease: CAG
4. Myotonic Dystrophy: CTG