Wednesday, December 08, 2021

Protons (53) a formula revised

Back in Protons (53) a formula I wrote down how to work out the F:N ratio of (even chain) fatty acids with varying double bonds:

F/N = (n-1-db)/(2n-1)

where n is the length of the carbon chain and db is the number of double bonds.

Oleic C18 is 18-1-1 divided by 36-1, ie 16/35 = 0.457
Linoleic 18-1-2 divided by 36-1, ie 15/35 = 0.423

This is fine up to C18 but C20 and above are targeted to peroxisomes rather than mitochondria so the need for an F:N ratio fades. Peroxisomes have their own signalling systems but research on them is in its infancy.

Anyhoo, Tucker mentioned off blog that during the multistep processing of double bonds there is a step which consumes NADPH. This will have to be re-reduced from the resultant NADP+ by the Krebs Cycle where NADH producing steps have iso enzymes capable of generating NADPH instead of NADH. That reduces the NADH supply to the electron transport chain by 1 NADH per double bond requiring NADPH, so complicates the formula.

The formula ends up as:

F/N = (n-1-db)/(2n-1-db)

It makes a relatively small change to the ratio as the denominator is a much larger number than the numerator.

Oleic acid, originally 0.457 becomes

18-1-1 divided by 36-1-1, ie 16/34 = 0.471

and linoleic acid, originally 0.423 becomes

18-1-2 divided by 36-1-2, ie 15/33 = 0.455

The latter is interesting as it moves linoleic acid upwards towards MUFA and the saturates because the denominator drops.

The value for caprylic (shortest saturate in common consumption) is 0.467 and with the new LA now at 0.455, they are getting closer. Also caprylic is now at lower F:N ratio than oleic. I just wonder if this is part of the explanation of the coconut based diets used by Surwit to induce obesity with LA still limited to 4% of calories...

Thanks to Tucker for the NADPH requirement insight.

Peter

12 comments:

Basti said...

Very interesting post.
A question arose:
What about butter now? Isnt it also rich in very short chain fats? Whats your opinion on butter when it comes to staying lean?

Peter said...

Basti, that is a question which has been kicking around in my head for several months now. Clearly, compared to PUFA rich spreads butter is slimming. But there are rodent models producing obesity at low linoleic acid levels provided butter oil is used as the bulk lipid source. Adding exogenous butyrate to low/moderate fat diets has effects on obesity which are variable. Choose your study and you can show either obesogenic or protective effects.

It's on my radar and Protons might do better than neuro-endocrine hypotheses to explain these.

Good point.

Peter

Malcolm said...

Peter, you mention "rodent models" there, and it reminds me of something I was thinking about recently. I vaguely remember someone saying that rat models are more useful than mouse models because ???, and yet most nutrition research uses mice. Do you have any thoughts on that?

Peter said...

I think Black 6 mice are a genetic train wreck, especially their defects with supercomplex assembly (the assembly protein is truncated and doesn't work) and Brad has pointed out their ANT exchanger defect. God know what else they have wrong with them but they are a good test of Protons, so I still love 'em. Outbred rats are probably more normal.

Peter

Luke said...

Awesome!!!
Thanks a lot.
It seems then that there arent big differences between oleic acid and LA...

Might it be that there are only 2 options to truly stay metabolically healthy and lean, namely:
1. To be super low carb,
2. When carbs are included, one must be as close to zero PUFA and MUFA as possible, by which i mean replacing any fat source that's not in beef with stearic acid in order to delute the MUFA from the beef fat.
Would you agree as well?

cavenewt said...

"...rat models are more useful than mouse models because ???..."

Peter: "I think Black 6 mice are a genetic train wreck, especially their defects with supercomplex assembly (the assembly protein is truncated and doesn't work) and Brad has pointed out their ANT exchanger defect. God know what else they have wrong with them but they are a good test of Protons, so I still love 'em. Outbred rats are probably more normal."

So, Peter, are you saying that rats and mice aren't really that different, the significant thing in terms of studies is the amount of genetic hanky-panky that's been done to them?

Not being able to swap your ants prompts some interesting visualizations.

Peter said...

Hi Luke, sadly I'm not really an extremist. I even eat a few vegetables occasionally nowadays! I do occasionally eat lean pork or chicken too, usually as a side dressing to a home made beef burger plus the dripping it was cooked in. I'm looking to do okay, I'm not aiming to do a David Sinclair and live for ever. I guess aggressiveness should be tailored to needs. I've never been heavy.

cave, I view it a little differently. People bred mice which got fat on high fat diets because that was a good marketing tool. The fact they stayed slim on anhydrous gruel probably helped. Having bred this type of mouse just by phenotype alone, we later found out quite how they were broken and how badly. I suspect failure to assemble super complexes limits their ability to generate RET from ETFdh inputs, hence obesity is easily achieved. ANT is clearer as ATP/ADP translocase, ie it is what exports ATP from mitochondria. Brad has written about it, I've not chased...

Peter

Malcolm said...

cave, yes, I was wondering if mice are herbivores (as wiki says!) and rats are omnivores, but it doesn't seem that simple. On a brief search, it looks like both will eat whatever they can get, e.g. including insects and eggs, so maybe there's no big difference in "natural" diet.

Seb94 said...

Hi, i just came across brad marshalls opinion that coconut oil doesnt provide, at least to a meaningful extend, the substrate for SCD1 and thus is very beneficial and helpful for loosing weight.
Do you think such things could counter the effects that the protons view would predict?

Peter said...

Hi seb94, have a look here,

https://high-fat-nutrition.blogspot.com/2020/05/surwit-diet-and-derivatives-3-5lj5-vs.html

based around the Jim Johnson lab’s work at https://pubmed.ncbi.nlm.nih.gov/28700945/

“Just to summarise the diets. Both had 4% of calories as PUFA, primarily linoleic acid. The 5LJ5 chow used a slow release carbohydrate (as uncooked ground wheat) combined with a little extra protein from soybean meal. The D12330 (Surwit type) diet was the usual hydrogenated coconut oil with maltodextrin/sucrose plus casein as the sole protein source.”

The fully saturated coconut oil produced pretty good obesity. The mice were about 50% from the Bl/6 background so watch for mitochondrial defects. The new F:N ratios give a handle on this MCT paradox as well as the butter paradox.

Peter

ali said...

Odd-carbon MCTs (such as Enanthic acid, Pelargonic acid and Undecylic acid) are anti-ketogenic (glucogenic), presumably because propionyl-CoA generated from oxidation may provide substrate for TCA cycle activity and glucose synthesis.
Even-carbon MCTs (such as Caprylic acid, Capric acid and Lauric acid) are ketogenic because excessive acetyl-CoA generated from oxidation are directed toward synthesis of ketones.
https://pubmed.ncbi.nlm.nih.gov/2794167

ali said...

Odd-carbon MCTs (such as Enanthic acid, Pelargonic acid and Undecylic acid) are anti-ketogenic (glucogenic), presumably because propionyl-CoA generated from oxidation may provide substrate for TCA cycle activity and glucose synthesis.
Even-carbon MCTs (such as Caprylic acid, Capric acid and Lauric acid) are ketogenic because excessive acetyl-CoA generated from oxidation are directed toward synthesis of ketones.
https://pubmed.ncbi.nlm.nih.gov/2794167