Page last updated: 2024-10-24

lysosomal protein catabolic process

Definition

Target type: biologicalprocess

Any cellular protein catabolic process that takes place in a lysosome. [GO_REF:0000062, GOC:bf, GOC:PARL, GOC:TermGenie, PMID:24334770]

Lysosomal protein catabolic process is a fundamental cellular pathway responsible for the breakdown of proteins within lysosomes, specialized membrane-bound organelles found in eukaryotic cells. It involves a series of tightly regulated steps that ensure the efficient and specific degradation of proteins that are no longer needed, damaged, or misfolded.

**1. Protein Targeting:** Proteins destined for lysosomal degradation are first tagged with ubiquitin, a small protein that acts as a signal for protein turnover. This tagging process is carried out by a complex of enzymes known as E1, E2, and E3 ligases. Ubiquitination is a crucial step as it directs the tagged protein towards the lysosome.

**2. Transport to Lysosomes:** Ubiquitinated proteins are then transported to lysosomes via a variety of pathways. One common route is through the endocytic pathway, where proteins are internalized from the cell surface and delivered to early endosomes. From there, they are sorted and transported to late endosomes, which eventually fuse with lysosomes. Another pathway involves autophagy, a process where cellular components, including proteins, are enclosed in double-membrane vesicles called autophagosomes. These autophagosomes then fuse with lysosomes for degradation.

**3. Lysosomal Entry:** Once inside the lysosome, proteins encounter a harsh acidic environment (pH 4.5-5.0) and a diverse array of hydrolytic enzymes, collectively known as lysosomal hydrolases. These enzymes are capable of breaking down various macromolecules, including proteins, carbohydrates, lipids, and nucleic acids.

**4. Protein Degradation:** The lysosomal hydrolases cleave peptide bonds within proteins, breaking them down into smaller peptides and amino acids. This breakdown is highly specific, with different hydrolases targeting specific amino acid sequences. The precise mechanism of protein degradation within the lysosome depends on the nature of the protein and the specific hydrolases involved. Some proteins may require unfolding or denaturation before being degraded, while others may be directly hydrolyzed.

**5. Recycling and Exocytosis:** The breakdown products of protein catabolism, primarily amino acids, are transported out of the lysosome and utilized for various cellular processes, such as protein synthesis or energy production. Lysosomes are also involved in the recycling of other cellular components, such as lipids and carbohydrates. In addition, some lysosomal contents can be released through exocytosis, a process where vesicles fuse with the plasma membrane and release their contents outside the cell.

**Overall, the lysosomal protein catabolic process is essential for maintaining cellular homeostasis, eliminating damaged or misfolded proteins, and providing building blocks for new protein synthesis. Its dysregulation can lead to various diseases, including lysosomal storage disorders, cancer, and neurodegenerative diseases.**'
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Proteins (1)

ProteinDefinitionTaxonomy
Dipeptidyl peptidase 2A dipeptidyl peptidase 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9UHL4]Homo sapiens (human)

Compounds (14)

CompoundDefinitionClassesRoles
valine-pyrrolididevaline-pyrrolidide: structure given in first source
sitagliptinsitagliptin : A triazolopyrazine that exhibits hypoglycemic activity.triazolopyrazine;
trifluorobenzene
EC 3.4.14.5 (dipeptidyl-peptidase IV) inhibitor;
environmental contaminant;
hypoglycemic agent;
serine proteinase inhibitor;
xenobiotic
vildagliptinamino acid amide
talabostattalabostat: an antineoplastic agent; structure in first source
nvp-dpp728
linagliptinlinagliptin : A xanthine that is 7H-xanthine bearing (4-methylquinazolin-2-yl)methyl, methyl, but-2-yn-1-yl and 3-aminopiperidin-1-yl substituents at positions 1, 3, 7 and 8 respectively (the R-enantiomer). Used for treatment of type II diabetes.

Linagliptin: A purine and quinazoline derivative that functions as an INCRETIN and DIPEPTIDYL-PEPTIDASE IV INHIBTOR. It is used as a HYPOGLYCEMIC AGENT in the treatment of TYPE II DIABETES MELLITUS.
aminopiperidine;
quinazolines
EC 3.4.14.5 (dipeptidyl-peptidase IV) inhibitor;
hypoglycemic agent
alanylpyrrolidine-boronic acid
uamc00039UAMC00039: dipeptidyl peptidase II inhibitor; structure in first source
bms 477118adamantanes;
azabicycloalkane;
monocarboxylic acid amide;
nitrile;
tertiary alcohol
EC 3.4.14.5 (dipeptidyl-peptidase IV) inhibitor;
hypoglycemic agent
alogliptinalogliptin : A piperidine that is 3-methyl-2,4-dioxo-3,4-dihydropyrimidine carrying additional 2-cyanobenzyl and 3-aminopiperidin-1-yl groups at positions 1 and 2 respectively (the R-enantiomer). Used in the form of its benzoate salt for treatment of type 2 diabetes.

alogliptin: structure in first source
nitrile;
piperidines;
primary amino compound;
pyrimidines
EC 3.4.14.5 (dipeptidyl-peptidase IV) inhibitor;
hypoglycemic agent
gosogliptinamino acid amide
anagliptinanagliptin: anagliptin hydrochloride salt is the active compoundamino acid amide
mk-3102pyrrolopyrazole
rpx7009RPX7009: a beta-lactamase inhibitor; structure in first source