Day 2 - Albumin, protein aggregation, chaperones, autophagy, protein misfolding diseases, PDIs, p53

Albumin is a what kind of carrier

Low affinity, low specificity, and high-capacity

Functions of Albumin (5)

Nutrient transport

Transporting hormones and extending half-life

Transporting drugs

Calcium ion homeostasis

Protecting plasma volume and cardiac output*

Protein aggregation causes neurological diseases such as (4)

Alzheimer’s, Parkinson’s, Huntington’s, Prior diseases

Pharmacological chaperones can be used to treat

diseases due to impaired degradation of proteins

Chaperones and aging

Can effect proteostasis and lead to protein aggregation if not working properly

Phagocytosis

Large molecules and pathogens can be engulfed to form phagosomes

Micropinocytosis

Nonspecific uptake of fluids containing micromolecules

Endocytosis

Macromolecules from ECF can be taken up by endosomes

Autophagy

Digestion of damaged organelles, macromolecules, and protein aggregatesA

Autophagy activated during

Starvation or cells deprived or nutrients

Selective Autophagy

Degrades damaged or unwanted cell organelle such as mitochrondria, ER, ribosomes, and invading pathogens

Major portion of cargo packaged into autophagosome with less amount of cytoplasm

Nonselective Autophagy

Large amount of cytoplasm is sequestered along with macromolecules into autophagosomeN

Nonselective autophagy happens during

starvation

Ubiquitin attaches itself to

target lysine of substrate

Parkinson’s Mutation

Pink1 or parkin cause form of early onset parkinson’s

Tay-Sachs Disease mutation

Point mutations in the HEXA gene

Cystic Fibrosis mutation

Lose phenylalanine following the deletion of three nucleotides in the CFTR gene

Munhmeyer disease mutation

Histidine replaces argining in the ACVR1 enzyme-linked receptor

Scurvy mutation

Hydroxylation of proline residues decreased

Huntington’s disease mutation

formation of repeated polyglutamine tract

Gaucher’s disease mutation

N370S or L444P to beta-Glucocerebrosidase

PDIs stand for

Protein Disulfide Isomerases

PDIs do what

Mediate disulfide bond formation during protein folding

PDIs: occurs between

cysteine residues

PDIs can also catalyze

Disulfide bond rearrangment and formation

p53

Tumor suppressor

Leads to the inhibition of S phase in cell cycle

Cycle stops at G1