Biochemistry- Cellular

cylcin-dependent kinases

constitutively expressed but inactive when not bound to cylcin

clyclin-CDK complexes

phosphorylate other proteins to coordinate cell cycle progession

cyclins

phase-specific regulatory proteins that activate CDKs when stimulated by growth factors

tumor suppressors

p53 inducts p21 which inhibits CDK which leads to Rb hypophosphorylation (activation) which leads to G1-S progression inhibition

permanent cell

remain in G knot; regenerate from stem cells; ex. neurons, skeletal and cardiac muscle, RBCs

stable (quiescent) cell

enter G1 when stimulated; ex. hepatocytes, lymphocytes, PCT, periosteal cells

labile cell

never go to G knot, divide rapidly with a short G1; most affected by chemotherapy; ex. bone marrow, gut epithelium, skin, hair follicles, germ cells

rough endoplasmic reticulum

site of exported protein synthesis and N-linked oligosaccharide addition to lysosomal and other proteins

nissl bodies

RER in neurons; make peptide neurotransmitters for secretion

free ribosomes

unattached to any membrane; site of synthesis of cytosolic, peroxisomal, and mitochondrial proteins

what areas are rich in RER

mucus-secreting goblet cells of small intestine and antibody-secreting plasma cells

smooth endoplasmic reticulum

site of steroid synthesis and detoxification; location of G6P

what areas are rich in SER

hepatocytes and steroid hormone-producing cells of adrenal cortex and gonads

i-cell disease (inclusion cell disease/ mucolipidosis type II)

inheritaed lysosomal storage disorder (autosomal recessive); defect in N-acetylglucosaminyl-1-phosphotransferase leads to failure of golgi to phosphorylate mannose residues (less mannose-6-phosphate) on glycoproteins leading to enzymes secreted etracellulary rather than to lysosomes; lysosomes are deficient in digestive enzymes which leads to buildup of cellular debris in lysoosmes (inclusion bodies); fatal in childhood

symptoms of i-cell disease

coarse facial features, gingival hyperplasia, corneal clouding, restricted joint movements, claw hand deformities, kyphoscoliosis, and increase plasma levels of lysosomal enzymes

single recognition particle (SRP)

abundant, cytosolic ribonucleoprotein that traffics polypeptide-ribosome complex from the cytosol to the RER

absent/dysfunctional SRP

accumulation of protein in cytosol

COPI

golgi → golgi (retrograde); cis Golgi → ER (one step back- retrograde)

COPII

ER → cis Golgi (anterograde); two steps forward (anterograde)

clathrin

trans golgi → lysosomes; plasma membrane → endosomes (receptor-mediated endocytosis)

peroxisome

membrane enclose organelle involved in:

• beta oxidation of very-long chain fatty acids (VLCFA)

• alpha oxidation of branches-chain fatty acids

• catabolism of amino acids and ethanol

• synthesis of bile acids and plasmalogens

zellwegeer syndrome

autosomal recessive disorder of peroxisome biogenesis due to mutated PEX genes (accumulation of pipecolic acid in peroxisomes)

symptoms of zellweger syndrome

hypotonia, seizures, jaundice, craniofacial dysmorphia, hepatomegaly, early death

refsum disease

autosomal recessive disorder of alpha oxidation; buildup of phytanic acid due to inability to degrade it; treatment: diet, plasmapheresis

symptoms of refsum disease

vision loss (retinitis pigmentosa), anosmia, hearing loss, peripheral neuropathy, icthyosis, and cardiac conduction defects

adrenoleukodystrophy

X-linked recessive disorder of beta oxidation due to mutation in ABCD1 gene; VLCFA buildup in adrenal glands, white (leuko) matter of brain, testes

symptoms of adrenoleukodystrophy

adrenal gland crisis, progressive loss of neurologic function, death

proteasome

barrel-shaped proteon complex that degrades polyubiquitin-tagged proteins; role in MHC mediated immune response

cytoskeletal elements

network of protein fibers within the cytoplasm that supports cell structure, cell, and organelle movement, and cell division

microfilaments

function in muscle contraction, cytokinesis, and phagocytosis

intermediate filaments

maintain cell structure

ex of microfilaments

actin, microvilli

ex of intermediate filaments

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

microtubules

movement, cell division

ex of microtubules

cilia, flagella, mitotic spindle, axonal trafficking, centrioles

microtubule

cylindrical outer structure composed of a helical array of polymerized heterodimers of alpha and beta tubulin; each dimer has 2 GTP bound; incorporated into flagella, cilia, mitotic spindles; involved in slow axoplasmic transport in neurons

molecular motor proteins

transport cellular cargo toward opposite ends of microtubule

dyenin

retrograde to microtubule (towards nucleus)

kinesin

anterograde to microtubule ( to periphery of cell)

viruses that use dyenin

clostridium tetani toxin, poliovirus, rabies virus, herpes simplex virus (HSV)

HSV reactivation occurs via

anterograde transport from cell body (kinesin mediated)

rate limiting step of peripheral nerve regeneration

slow anterograde transport

drugs that act on microtubules

microtubules get constructed very terribly

• mebendazole (antiheminthic)

• griseofulvin (antifungal)

• cochicine (antigout)

• vinca alkaloids (anticancer)

• taxane (anticancer)

motile cilia

9 doublet + 2 single arrangement of microtubules (axoneme)

basal body

base of iclium below cell membrane; 9 microtubule triplets with no central microtubules

nonmotile (primary) cilia

work as chemical signal sensors; role in signal transduction and cell growth control

dysgenesis of primary cilia leads to

polycystic kidney disease, mitral valve prolapse, retinal degeneration

axonemal dynein

ATPase that links peripheral 9 doublets and causes bending of cilium by differential sliding of doublets

gap junctions

enable coordinated ciliary movement

primary ciliary dyskinesia

autosomal recessive; dynein arm defect → immotile cilia→ dysfuncitonal ciliated epihelia

symptoms of primary ciliary dyskinesia

developmental abnormalities due to impaired migration and orientation, recurrent infections (impaired ciliary clearance of debris/pathogens), infertility (increased risk of ectopic pregnancy due to dysfunctional fallogian tube cilia, immotile spermatozoa)

lab findings of primary ciliary dyskinesia

decrease nasal nitric oxide (used as screening test)

digoxin

inhibits Na+/K+-ATPase → indirect inhibition of Na+/Ca2+ exchange → increased intracellular calcium → increase cardiac contractility

collagen

most abundant protein in human body; modified by posttranslational modification; organizes and strengthens extracellular matrix; types : SCAB

type 1 collagen

most common; Skeleton (bone, skin, tendon, dentin, fascia, cornea, late wound repair)

type 2 collagen

Cartilage, vitreous body, nucleus pulposus

type 3 collagen

Arteries (reticulin- skin, blood vessels, uterus, fetal tissue, early wound repair)

type 4 collagen

Basement membrane/ basal lamina (glomerulus, cochlea), lens

osteogenesis imperfecta

genetic bone disorder caused by variety of gene defects (most ocmmon COL1A1 and COL1A2); most common form is autosomal dominant with decrease i nproduction of normal type 1 collagen (altered triple helix formation)sy

symptoms of osteogenesis imperfecta

BITE (Bones, I (eye), Teeth, Ear)

• multiple fractures and bone deformities after minimal trauma

• blue sclerae due to thin, translucent scleral collagen revealing chroidal veins

• opalescent teeth that wear easily due to lack of dentin (dentinogenesis imperfecta)

• hearing loss (abnormal ossicles)

ehlers-danlos syndrome

faulty collagen synthesis causes skin to be hyperextensible and often thin or transparent, joints to be hypermobile, and tendency to bleed; multiple types; can be caused by procollagen peptidase deficiency; inheritance and severity vary

hypermobility ehlers-danlos syndrome

joint instability; most common

classical type ehlers-danlos syndrome

joint and skin symptoms; caused by mutation in type 5 collagen (ex COL5A1, COL5A2)

vascular ehlers-danlos syndrome

fragile tissues including vessels, muscles, and organs that are prone to rupture; mutations in type 3 procollagen ( ex. COL3A1)

Menkes disease

X-linked recessive connective tissue disease caused by impaired copper absorption and transport due to defective ATP7A

symptoms of menkes disease

leads to decrease activity of lysyl oxidase → defective collagen cross-linking → brittle/kinky hair, grwoth and developmental delay, hypotonia, increased risk of cerebral aneurysms

elastin

stretchy protein within skin, lungs, large arteries, elastic ligaments, vocal cords, epiglottis, ligamenta flaval rich in nonhydroxylated proline, glycine, and lysine

ligamenta flava

connect vertebrae → relaxed and stretched conformations

marfan syndrome

autosomal dominant connective tissue disorder affecting skeleton, heart, and eyes; FBN1 gene mutation of chromosome fifteennresults in defective fibrillin-1

symptoms of marfan syndrome

tall wiht long extremities, chest wall deformity (pectus carinatum or excavatum), hypermobile joints, long/tapering fingers and toes, cystic medial necrosis of aorta, aortic root aneurysm rupture or disection, mitral volve prolapse, increased risk of spontaneous pneumothorax

arachnodactyly

long, taperin fingers and toes

pectus carinatum

pigeon chest

homocystinuria

most commonly due to cystathionine synthase deficiency leading to homocysteine buildup; autosomal recessive

symptoms of homocystinuria

pectus deformity, tall stature, increase arm: height ratio, decreased upper:lower body segment ratio, arachnodactyly, joint hyperlaxity, skin hyperelasticity, scoliosis, fair complexion, decreased intellect, thrombosis