Cellular Biochemistry

Question 1

Which are the cell cycle phases?

Answer 1

M (mitosis [prophase, promethaphase, metaphase, anaphase, telophase] and cytokinesis [cytoplasm splits in two]).
M=menor, shortest.

G1 & G0 = Growth, variable duration.

S = DNA Synthesis.

Cell cycle is regulated by cyclins, CDK and tumor suppressors.

Question 2

What are CDK?

Answer 2

Families of protein kinases, involved in regulating transcription, mRNA processing, and the differentiation of nerve cells. They are present in all known eukaryotes.
They are constitutive and inactive.

Question 3

What are cyclins?

Answer 3

Regulatory proteins, phase specific, activate CDK.

Question 4

What are the tumor suppressors?

Answer 4

p53 induces p21 to inhibit CDK

Hypophosphorylation of Rb (activation)
Inhibition of G1-S progression.

Unrestrained cell division if alterations (Li-Fraumeni Sx).

The growth factors bind tyrosine kinase receptors to transition from G1 to S.

Question 5

How are cells classified?

Answer 5

Permanent, stable/quiescent and labile.

Question 6

How does the RER work?

Answer 6

It synthesizes the secretory proteins and adds N-linked oligosaccharides to lysosomal and proteins.

In neurons it’s called Nissl body, creates peptide neurotransmitters for secretion.

The free ribosomes (unattached) synthesize cytosolic, peroxisomal and mitochondrial proteins.

They are abundant in mucus-secreting goblet cells in intestine and antibody-secreting plasma cells.

Question 7

How does the SER work?

Answer 7

It synthesizes steroids and detox drugs and poisons. No surface ribosomes.

Abundant in sites of steroid hormone production (hepatocytes, adrenal cortex and gonads).

Question 8

What does the Golgi complex do?

Answer 8

Distribution center for proteins and lipids from ER to vesicles and plasma membrane.

It modifies the N-oligosaccharides on asparagine, the O-oligosaccharides on serine and threonine.

It adds mannose-6-phosphate to proteins that go to lysosomes.

Question 9

What are the endosomes?

Answer 9

Sorting centers from material from the outside or from the Golgi to lysosomes or back to the membrane. Transport.

Question 10

What is the Signal Recognition Particle (SRP)?

Answer 10

A cytosolic nucleoprotein that takes polypeptide-ribosome complexes from cytosol to RER. If alteration: accumulation in cytosol.

Question 11

What are the Vesicular trafficking proteins?

Answer 11

Membrane proteins that regulate movement of molecules across the vesicle membrane.

Question 12

Which are the vesicular trafficking proteins pathways?

Answer 12

COP 1: (Cytosolic coat protein complex). Retrograde, cis-Golgi to ER.

COP 2: RER to cis-Golgi (anterograde).

Clathrin: Trans Golgi to lysosomes, plasma membrane to endosomes (receptor mediated endocytosis).

Question 13

What are peroxisomes?

Answer 13

Membrane organelles that participate in:
ß-oxidation of VLCFA
alpha-oxidation (strictly peroxisomal process)
Catabolism of ethanol, branched fatty acids and aa.
Synthesis of cholesterol, bile acids and plasmalogens (membrane phospholipid in brain white matter).

Question 14

What are microfilaments for?

Answer 14

Actin, microvilli. Muscle contraction and cytokinesis.

Question 15

What do intermediate filaments do?

Answer 15

They maintain the cell structure.

Vimentin, desmin, cytokeratin, lamins, glial fibrillary acidic protein (GFAP), neurofilaments.

Question 16

What is the microtubules structure?

Answer 16

Cylindrical structure of helical array of polymerized heterodimers of alpha and beta tubulin. 
Each dimer has 2 GTP bound.
Into flagella, cilia, mitotic spindles.
Grows slowly, collapses quickly.
Slow axoplasmic transport in neurons.

Question 17

Drugs that act on microtubules?

Answer 17

[Microtubules Get Constructed Very Poorly]

Mebendazole
Griseofluvin
Colchicine
Vincristine/Vinblastine
Paclitaxel

Question 18

What are the molecular motor proteins in microtubles?

Answer 18

They transport cargo toward opposite ends of microtubule tracks.

Dynein: retrograde to microtubule.
Kinesin: aterograde to microtubule.

Negative are Near to Nucleus.
Positive end Points to Periphery.

Question 19

What is the cilia structure?

Answer 19

9 doublets + 2 singlet arrangement of microtubules.

Basal body: below cell membrane. 9 microtubule triplets, no central microtubules.

Axonemal dynein-ATPase links peripheral 9 doublets and cause bending of cilium by differential sliding of doublets.

Gap junctions enable coordinated ciliary movement.

Question 20

What is the Kartagener syndrome?

Answer 20

1º ciliary dyskinesia. Cilia are immobile due to a dynein arm defect. AR. Low fertility in both sexes (immotile sperm and dysfunctional fallopian tubes cilia).
Major risk of ectopic pregnancy.
Bronchiectasis, recurrent sinusitis, chronic ear infections, conductive hearing loss, situs inversus.
As screening test: low nasal nitric oxide.

No dynein.

Question 21

How does the Na-K pump work?

Answer 21

In plasma membrane, ATP side on cytosol.
Each ATP consumed, 3Na go out the cell (pump phosphorylated) and 2K enter (dephosphorylated).

Pumpkin Pump K In.
Ouabain (cardiac glycoside) inhibits it by binding to K site.

Digoxin and digitoxin inhibit the pump, causing an indirect inhibition of Na/Ca exchange, augmenting Ca concentration and therefore cardiac contractility.

Question 22

What is collagen and which are the types?

Answer 22

Is the most abundant protein, modified by posttranslational modification.

I : 90%, Bone, Skin, Tendons, dentin, fascia, cornea, late wound repair.
Low in osteogenesis imperfecta I.

II: Cartilage, vitreous body, nucleus pulposus.
(Cartwolage)

III: Reticulin-skin, blood vessels, uterus, fetal tissue, granulation tissue.
Deficit in uncommon, Vascular type of Ehlers-Danlos (ThreE D). III

IV: Basement membrane, lens.
Defective in Alport sx, targeted by autoantibodies in Goodpasture.

(Be So Totally Cool, Read Books).

Question 23

How is the collagen synthesis?

Answer 23

Collagen is 1/3 glycine.
It starts with the translation of alpha chains (preprocollagen).
Gly-X-Y (X and Y are proline or lysine).

Hydroxylation: of specific X and Y residues, requieres vitamin C (scurvy when deficit).

Glycosylation: pro-alpha-chain hydroxylysine residues and formation of procollagen via hydrogen and disulfide bonds. Triple helix of 3 collagen α chains.
If trouble in forming the triple helix: osteogenesis imperfecta.

Exocytosis: Procollagen into extracellular space.

Proteolytic processing: Cleavage of disulfide rich terminal regions: insoluble tropocollagen.
If problems with cleavage: Ehlers-Danlos.

Cross-linking: reinforcement of staggered tropocollagen by covalent lysine-hydroxylysine cross-linkage (by copper lysyl oxidase) to make collagen fibrils.
If problem: Ehlers-Danlos or Menkes disease.

Question 24

What is Osteogenesis imperfecta?

Answer 24

The brittle bone disease.
AD mostly, low production of type I collagen.
Mutations in COL1A1, COL1A2.

Fractures and bone deformities with minimal trauma, blue sclerae (translucent connective tissue over choroidal veins), teeth deformities like opalescent teeth that wears easily (lack of dentin, dentinogenesis imperfecta), hearing loss due to abdnormal ossicles.

Biphosphonates reduce risk of fractures.

Patients can’t BITE
Bone
I (eye)
Teeth
Ear

Question 25

What is the Ehlers-Danlos syndrome?

Answer 25

Multiple types, varying severity and inheritance.
AD or AR.

Hypermobility type: the most common.
Joint instability.

Classical type: joint and skin. type V (COL5A1, COL5A2).

Vascular type: fragile vessels, muscles, organs (rupture, aneurisms…) type III procollagen (COL3A1).

Question 26

What is Menkes disease?

Answer 26

X linked recessive. Impaired copper absorption and transport, defective Menkes protein (ATP7A) (Wilson is ATP7B).
Low activity of lysyl oxidase (uses copper as cofactor): defective collagen.
Brittle, kinky hair, growth retardation and hypotonia.

Question 27

What is elastin? What does it do?

Answer 27

Skin, lungs, large arteries, elastic ligaments, vocal cords, ligamenta flava.

Rich in nonhydroxylated proline, gly, lysine residues vs hydroxylated residues of collagen.

Tropoelastin with fibrillin scaffolding.

Cross-linking extracellularly, gives its elastic properties.

Broken down by elastase, inhibited by α1-antitrypsin.
Its deficit cause elastase overactivity: emphysema.

With age: less dermal collagen and elastin, less synthesis of collagen fibrils, crosslinking normal.

Question 28

What is the Marfan syndrome?

Answer 28

AD, affects skeleton, heart, eyes.
FBN1 gene mutation on 15 cromosome: defective fibrillin (glycoprotein that sheaths around elastin).
Tall, long extremities, pectus carinatum or excavatum, hypermobile joints, long tapering fingers, arachnodactyly, cystic medial necrosis of aorta, aortic incopetence and dissecting aortic aneurysms, mitral prolapse.
Subluxation of lenses, upward and temporally (in homocystinuria is downward and medially).