On Cellular Organization and Respiration
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ATP use:
- ATP + H₂O ⇉ ADP + Pi + H⁺
And 2 methods of regeneration:
'Substrate-level' phosphorylation:
- ADP + R-OP + *H⁺ → ATP + R-OH
(R for "Root")
Oxidative phosphorylation:
- ADP + Pi + H⁺ → ATP + H₂O
*Whether a H⁺ is consumed will depend on the reaction.
Creatine cycling does consume (→) and produce (←) H⁺:
- ADP + (Creatine-OP) + H⁺ ⇄ ATP + (Creatine-OH)
Throughout cellular respiration, it's tricky..
Enzyme Participants Dir. Participants HK ADP + R-OP + H⁺ ← ATP + R-OH PFK ADP + R-OP + H⁺ ← ATP + R-OH PGK ADP + R-OP + H⁺→ ATP + R-O⁻ PK ADP + R-OP + *H⁺→ ATP + R-O *But a hydrogen is incorporated elsewhere (R-CH₂ → R-CH₃):
We could argue that glycolysis metabolites become ionized as soon as phosphate is attached to them (early on in glycoylsis), and this contributes to their trapping in cells. However, the definite ionization occurs when phosphates start to be detached in PGK, where crapoxylates are formed (note in the table how H⁺ aren't consumed against expectation).
It's for the phosphorylation steps that you'll find a one-way arrow in diagrams, deeming them irreversible (except for PGK). However, if this was the case in all tissues, glucose resynthesis wouldn't be possible. As an example, the reactions of HK and PFK can be undone through phosphorylases that work as hydrolases:
- Glycolite-OP + H₂O → Glycolite-OH + Pi
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In oxidative phosphorylation, the PO₃⁺ (of inorganic phosphate; Pi) goes towards ADP, and OH⁻ (also from Pi) combines with H⁺ to form H₂O.
- ADP + Pi + H⁺ → ATP + H₂O
With substrate-level phosphorylation in mitochondria, we have a variation of it. SCS reaction (omitting the succinyl group):
- 'ADP' + Pi + CoAS⁻ → 'ATP' + CoASH
As before, the PO₃⁺ (of inorganic phosphate; Pi) goes towards ADP, but here OH⁻ doesn't combine with H⁺ to form H₂O. Rather, oxygen gets incorporated to yield succinate, and H⁺ is accepted by CoA instead of released immediately in free form. No additional H⁺ is consumed.
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Therefore, lactate formation aside, increase reliance on substrate-level phosphorylation for ATP resynthesis goes without the immediate compensatory H⁺ consumption, although complete metabolism should be an overall H⁺-consuming process.It's worth noting the complicators.
Free phosphates will occur as mixed species that take up more or less H⁺ depending on its concentration, and differences in acidity between compartments will affect the composition.
We also know that most of the ATP is produced in mitochondria and consumed in the cytosol. The synthesis of ATP with H⁺ consumption occurs in a more alkaline environment relative to where most of ATP is hydrolyzed. At some stage, the extra H⁺ taken up by phosphates in the cytosol will have to be released when the phosphates in question return to mitochondria. -
@Amazoniac Thanks!
It is on my reading list now! Main goal not to side-track
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Does Aerobic Respiration Produce Carbon Dioxide or Hydrogen Ion and Bicarbonate?
The majority of CO₂ in the body circulates as the hydrocarbonate ion:
Carbon dioxide and derivatives Content Hydrocarbonate ion (HCO₃⁻) ~70% Carbamates (protein-bound; R-NH-CO₂) ~23% Carbon dioxide (CO₂) ~7% Carbonic acid (H₂CO₃) <1% Organic anions are considered alkalinizing when they are hydrocarbonate precursors. However, prior to its formation, CO₂ has to be hydrated, and for every hydrocarbonate ion derived from CO₂, a H⁺ is released in the system:
- CO₂ + H₂O ⇄ H₂CO₃ ⇄ H⁺ + HCO₃⁻
The H⁺ are temporarily sequestered, but complexation doesn't negate it.
It's easy to overlook the H⁺ load for not being apparent in circulation, where normal levels are:
- [HCO₃⁻]: 22-32 mmol/L
- [H⁺]: 0.000036-0.000043 mmol/L (from pH: 7.44-7.37)
Far from a 1:1 ratio.
It can be argued that hydrocarbonate precursors alkalinize for consuming H⁺ in priming molecules for complete oxidation (into CO₂ and H₂O), which is true, but the consumption is compensated when the equivalent of carbonic acid molecules appear in the system.
Unlike non-volatile acids that can remain paired by a corresponding counter-ion until elimination (example: sodium sulfate), the occurrence of carbonic acid or variants yields CO₂ and H₂O. This CO₂ leaves the body, and the original pairing cation is left as unpaired as residue (example: sodium
citrate).To maintain ion neutrality and rebalance, the body may try to lower cations, which would affect H⁺ concentration, and conserve anions, including hydrocarbonate. Fluid redistribution from the excess cation can also dilute H⁺. The hydrocarbonate are first and foremost carbonic acid precursors, so we need explanations along these lines.
@Lejeboca said in On Cellular Organization and Respiration:
@Amazoniac Thanks!
It is on my reading list now! Main goal not to side-trackСпасибо за визит.
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Each turn of the TCA cycle eliminates 2 carbons in consecutive (oxidative) decrapoxylation steps:
- IDH: isocitrate → ketoglutarate* + CO₂
- KGDH: ketoglutarate* → succinyl(CoA) + CO₂
A peculiarity of the TCA cycle is that succinate and (its product) fumarate are symmetrical molecules (⇈). Since this property applies to both of them, we can tell that succinate dehydrogenase modifies succinate evenly.
The next reaction is the conversion of fumarate to malate, where asymmetry appears. Even though fumarate is symmetrical, it contains newer or older atoms throughout the molecule. Depending on which side of fumarate is primarily changed after fumarase, the carbon stay in the cycle will differ.
This gives an idea:
I've adapted it for ease of tracing and until completion:
Therefore, the original carbons (from a given acetyl group) aren't eliminated straight away. They remain intact on the 1st turn, and the chances of their complete elimination appear to be:
- 50% on the 3rd turn
- 25% on the 4th turn
- 12.5% on the 5th turn
- 6.25% on the 6th turn
- ...
*Ketoglutarates:
- 2-oxoglutarate = a-ketoglutarate
- 3-oxoglutarate = b-ketoglutarate
Alpha refers to the second carbon because the first is the crapoxyl group, that's disconsidered in counting (similar to beta-oxidation).
Urine Organic Acids as Potential Biomarkers for Autism-Spectrum Disorder in Chinese Children
"[..]3-oxoglutarate, a common metabolite of yeast and fungi (Thomas et al., 2010; MacFabe et al., 2011; Kocovska et al., 2012), was significantly lower in children with autism. The low concentrations of both carboxycitric acid and 3-oxoglutarate that we observed in urine from autistic patients could be due to increased uptake of these compounds across the blood-brain barrier of the brain. Our results are consistent with previous studies that showed anti-fungal treatments for children with autism can effectively reduce the amounts of corresponding organic acid indicators (Cobb and Cobb, 2010), and suggests that gastrointestinal yeast could provide a basis for dietary adjustments such as gluten/casein-free diets that are important for children’s nervous system development and could mitigate autism symptoms. 3-oxoglutarate in urine is associated with the presence of harmful gut flora such as Candida albicans (Schmidt, 1994)."
It's fine to omit the 'alpha' prefix from ketoglutarate for the same reason that we only need to clarify which Paris we're going to when it's not the one in France.
