What is Oxphos in cancer?
Oxidative phosphorylation (OXPHOS) occurs in mitochondria and leads to efficient generation of ATP. OXPHOS is an active pathway in tumors and cancer stem cells. Several inhibitors or the various subunits of the mitochondrial electron transport complexes can serve as candidates for tumor therapy.
What is ADH and ALDH?
Ethanol is metabolized to acetaldehyde by alcohol dehydrogenase (ADH). The enzyme responsible for oxidation of acetaldehyde is aldehyde dehydrogenase (ALDH). Both formation and degradation of acetaldehyde depends on the activity of these enzymes.
Which organelle contains the enzymes ADH and ALDH?
The mitochondria play an important role in the alcohol metabolism via the enzyme ALDH; this enzyme catalyzes the conversion of acetaldehyde into acetate.
How does alcohol dehydrogenase break down alcohol?
Most alcohol is broken down, or metabolised, by an enzyme in your liver cells known as alcohol dehydrogenase (ADH). ADH breaks down alcohol into acetaldehyde, and then another enzyme, aldehyde dehydrogenase (ALDH), rapidly breaks down acetaldehyde into acetate.
What are inhibitors of oxidative phosphorylation?
Inhibitors
| Compounds | Use | Effect on oxidative phosphorylation |
|---|---|---|
| Malonate and oxaloacetate | Poisons | Competitive inhibitors of succinate dehydrogenase (complex II). |
| Antimycin A | Piscicide | Binds to the Qi site of cytochrome c reductase, thereby inhibiting the oxidation of ubiquinol. |
What is a hallmark of cancer cells?
The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis.
What type of enzyme is ADH?
Alcohol dehydrogenases (ADH) (EC 1.1. 1.1) are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+) to NADH.
What does ALDH stand for?
ALDH
| Acronym | Definition |
|---|---|
| ALDH | Aldehyde Dehydrogenase |
What is peroxisome and its function?
Peroxisomes are organelles that sequester diverse oxidative reactions and play important roles in metabolism, reactive oxygen species detoxification, and signaling. Oxidative pathways housed in peroxisomes include fatty acid β-oxidation, which contributes to embryogenesis, seedling growth, and stomatal opening.
Why do alcoholics have more smooth ER?
Large amounts of smooth ER are found in liver cells where one of its main functions is to detoxify products of natural metabolism and to endeavour to detoxify overloads of ethanol derived from excess alcoholic drinking and also barbiturates from drug overdose.
What inhibits alcohol dehydrogenase?
Alcohol dehydrogenase is an important enzyme in the visual cycle, being involved in the retinol–retinal conversion, and in this communication it has been established that this thiol-containing enzyme is competitively inhibited by chloroquine.
What type of enzyme is alcohol dehydrogenase?
Alcohol dehydrogenases are a class of zinc enzymes which catalyse the oxidation of primary and secondary alcohols to the corresponding aldehyde or ketone by the transfer of a hydride anion to NAD+ with release of a proton.
How are OXPHOS inhibitors used in the treatment of cancer?
OXPHOS inhibitors could therefore be used to target cancer subtypes in which OXPHOS is upregulated and to alleviate therapeutically adverse tumor hypoxia. Several drugs including metformin, atovaquone, and arsenic trioxide are used clinically for non-oncologic indications, but emerging data demonstrate their potential use as OXPHOS inhibitors.
How is OXPHOS downregulation related to cancer?
OXPHOS downregulation is associated with poor clinical outcome across all cancer types and correlates with a gene signature characteristic of invasive and metastatic tumors ( 11 ).
Is there an inhibitor of oxidative phosphorylation that exploits cancer vulnerability?
An inhibitor of oxidative phosphorylation exploits cancer vulnerability. Extensive efforts have focused on therapeutic targeting of glycolysis, whereas drugging mitochondrial oxidative phosphorylation (OXPHOS) has remained largely unexplored, partly owing to an incomplete understanding of tumor contexts in which OXPHOS is essential.
Can a mtDNA mutation cause a decrease in OXPHOS?
It is also important to note that many mtDNA mutations do not simply cause a decrease in OXPHOS but may facilitate adaptation to the bioenergetic demands of the tumor microenvironment without altering OXPHOS ( 6 ).