The oxidative stress caused by these rapidly proliferating cancer cells induces glycolysis and autophagy in the surrounding stromal cells that generates catabolites, such as lactate or ketones, which in turn are taken up by anabolic cancer cells, and used to fuel mitochondrial metabolism and ATP production (reverse Warburg effect).
Cursory consideration of the TCA cycle (Chap. 9) reminds us that absent NADH and FADH2 reoxidation, this cycle would quickly become substrate-limited and would promptly cease to function. Likewise, ATP is essential to drive biosynthesis and fuel the molecular motors that translocate macromolecules and transport metabolites. How then do cells prevent massive accumulation of NADH and FADH2, while continually resupplying sufficient ATP? This conundrum is circumvented in mitochondria, not by substrate-level reactions analogous to glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase within the cytosol, but by a series of redox reactions that electrochemically generate transmembrane proton gradients that are ultimately mechanochemically coupled to ATP synthesis. The latter reactions take place within mitochondria, and this chapter focuses on the logical arrangement and operation of the electron transport system and oxidative phosphorylation. A similar system allows chloroplasts to harvest photic energy electrochemically, again generating transmembrane proton gradients that are likewise coupled to ATP synthesis (Chap. 15).
THF-derived carbon units are primarily used for nucleotide synthesis in the cytosol, new methods for tracing NAPDH compartmentalization indicate that serine is predominantly utilized in the mitochondria of mammalian cells to generate NADPH[,,].
The folate cycle is essential for synthesis of adenosine, guanosine and thymidylate, and can contribute to mitochondrial NADH, NADPH and ATP regeneration.
Most cells default to the mitochondrial-to-cytosol directionality of the folate cycle, but when the mitochondrial pathway is inhibited, the cytosolic pathway can work in reverse to support nucleotide synthesis and proliferation.
A major role of ATP is
in , supplying the needed energy to synthesize the
multi-thousands of types of macromolecules that the cell needs to exist.
When the ATP converts to ADP, the ATP is said to be .
Then the ADP is usually immediately recycled in the mitochondria where
it is recharged and comes out again as ATP.
Flavopiridol is a synthetic flavone that is known to accumulate in mitochondria and induce selective killing of leukemic cells through pathways linked to mitochondrial mediated apoptosis and necrosis.
Plants can also produce
ATP in this manner in their mitochondria but plants can also produce
ATP by using the energy of sunlight in chloroplasts as discussed later.
In the case of eukaryotic animals the energy comes from food which is
converted to pyruvate and then to (acetyl CoA).
Acetyl CoA then enters the Krebs cycle which releases energy that results
in the conversion of ADP back into ATP.
Fatty acid oxidationFatty acid oxidation is a set of cyclical series of long-chain fatty acids oxidations that occur in the mitochondria resulting in production of short-chain fatty acids, generating NADH, FADH2 and acetyl-CoA for biosynthetic pathways and produce ATP.
Since bacteria lack mitochondria, as well as an internal
membrane system, they must produce ATP in their cell membrane which
they do by two basic steps.
Normal cells primarily metabolize glucose to pyruvate for growthand survival, followed by complete oxidation of pyruvate to CO2 through the TCA cycle and the oxidative phosphorilation process in the mitochondria,generating 36 ATPs per glucose.
The location of the ATP producing
system is only one of many major contrasts that exist between bacterial
cell membranes and mitochondria.
Normal cells primarily metabolize glucose to pyruvate for growth and survival, followed by complete oxidation of pyruvate to CO2 through the TCA cycle and the oxidative phosphorilation process in the mitochondria, generating 36 ATPs per glucose.
Once again plausible transitional forms
have never been found that can link these two forms of ATP production
from the photosynthesis system.