USMLE - BioChem Part 2

Site of steroid synthesis and detoxification of drugs and poisons

Liver hepatocytes and steroid hormone-producing cells of adrenal cortex are rich in SER

Modifies N-oligosaccharides on Asparagine

| Adds O-oligosaccharides on Serine and Threonine

Mannose-6-Phosphate added in lysosomes

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

COPI: Retrograde (Golgi --> Golgi, Golgi --> ER)

COPII: Anterograde (Golgi --> Golgi, ER --> Golgi)

Clathrin: trans-Golgi --> lysosomes, Plasma membrane --> Endosomes (receptor mediated endocytosis)

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

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

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

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

Kinesin: anterograde in 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)

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

9+2 arrangement of MTs. 9 doublets of MTs + 2 individual MT in middle

Dynein links peripheral 9 doublets

Kartagener's Syndrome

Immotile cilia due to dynein arm defect

Male infertility, ↓ female fertility, Bronchiectasis, Recurrent sinusitis

Associated with sinus inversus

Microvilli, Muscle contraction, Cytokinesis, Adherens junctions

Vimentin: Connective tissue

Desmin: Muscle

Cytokeratin: Epithelial cells

Glial Fibrillary Acid Protein (GFAP): NeuroGlia

Neurofilaments: Neurons

Cholesterol, Phospholipids, Sphingolipids, Glycolipids, and Proteins

When open to extracellular side

Inhibits Na/K ATPase by binding to K site

Digoxin and Digitoxin

| Inhibits Na/K ATPase leading indirectly to increased Ca --> increased contractility

Collagen

Most common collagen (90%)

Bone, Skin, Tendon, Dentin, Fascia, Cornea, Late Wound Repair

Defective in Osteogenesis Imperfecta

Cartilage (including hyaline, Vitreous body, Nucleus pulposus

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

Ehlers-Danlos (vascular type)

Basement membrane (basal lamina)

Alport Syndrome

"Be (So Totally) Cool, Read Books"

I: Bone, Skin, Tendon

II: Cartilage

III: Reticulin

IV: Basement Membrane

RER: translation of α chains (preprocollagen)

ER: Hydroxylation of specific proline and lysine residues (requires VitC)

ER: Glycosylation of pro-α-chain hydroxylysine residues

Formation of procollagen via hydrogen and disulfide bonds (triple helix of 3 α chains)

Exocytosis

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)

Cleavage of disulfide rich terminal regions of procollagen forming insoluble tropocollagen

Reinforcement of many staggered tropocollagen molecules by covalent lysine-hydroxylysine cross linkage (by Cu2+ containing lysyl oxidase)

Type III or V defect

Problems with cross linking by Cu2+ containing lysyl oxidase

Hyperextensible skin, Easy bleeding and bruising, Hypermobile joint 6 types

Can be AD or AR

Joint dislocation, berry aneurysm, organ rupture

Marfan's

Scurvy

Type IV

Variety of genetic defects but most commonly X linked recessive

Progressive hereditary nephritis, deafness, and ocular disturbances

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)

Reduced collagen and elastin production

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

SNoW DRoP

Southern - DNA

Northern - RNA

Western - Protein

RNA used

Protein used

Identifies DNA-Binding Proteins using labeled oligonucleotide probes

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

Can detect SNPs

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

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)

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

30S ribosome

| Binds complimentary mRNA to initiate translation - Shine Delgarno Sequence

Glucose --/ AC, leading to a decrease in cAMP

| When glucose is not present, cAMP is high and cAMP-CAP complex promotes transcription

Lactic Acidosis with an Anion Gap

| Tissue Hypoxia --> Anaerobic Respiration and impairment of OxPhos

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

Hypothyroidism

| Congenital heart defects

dsDNA breaks and free radicals

Metabolizes Uric Acid into Allantoin which is more soluble

| Tumor Lysis Syndrome