the metabolism of lipids

[coconinoz]

i've been learning quite a bit from a members only forum -- while questions, doubts, hypothetical alternative routes, etc. keep building up in my mind, that is

so why in the world, 1 may wonder, you don't ask your questions over there instead of bothering us here? in fact, we were doing just fine until you joined...

well, the thing is i don't function at my best in a grammar school kind of environment: don't have a single apple on hand to offer to the teacher (aka forum manager), ms. me, a serious problem now that she's coming out of the closet as a fructose lover

so now that i somehow got my foot in the door here, i can try & lay out the issues on the raw table

(a)
~ "burning" TG for fatty acids vs "burning" TG for glucose

what is this, precisely?

(in my ignorance, i had thought that what is burned for fuel is not the TG themselves but the free fatty acids released from them)
what are both the conditions in & results from burning TG for fatty acids or for glucose?

(b)
~ the complete metabolism of fatty acids calls for not only oxygen but also fructose; the incomplete metabolism of fatty acids is, for some reason, undesirable

again: what is this, precisely?

1 thing i seem to have gathered is that the incomplete metabolism of fatty acids would result in a BG cascade, something as bad as the plague it's claimed
why should 1 live with a BG perpetually constrained within a narrow range, sort of like being in a straightjacket, locked in a "neutral" pose?

here's 1 speculation/hypothesis my mind has come up with:
if fructose is actually needed in order to metabolize fatty acids completely & if this fructose must necessarily come from food ingested together with lipids...
then we humans are not doomed to eat avocado, apricot, maca, agave nectar, etc; (all high in fructose)
rather, we can eat raw liver or kidney from wild or 100% pastured (grainless) mammals while letting our animal friends eat all the fruit & greens to their happy satisfaction -- this is what i call the ecological food chain

of course, my hypothesis hinges upon a question whose answer i don't currently know: are animals, the kind of animals we eat, ketone adapted?
ketones are said to be a form of fructose; if the animal is ketone adapted, or at least in ketosis, then some % of the carbs in its raw liver & kidneys may be ketones, i.e. fructose, dietary fructose for us humans who eat according to the ecological food chain

any thoughts?

[Nicola]

I think you have been into the "SaturatedFatForHealth" Yahoo group; "incomplete metabolism of fatty acids"; I wonder if animals have to worry about that or being in "no mans land"?

Nicola

[xylothrill]

Welcome Coconinoz,

As for (a), You are correct. The entire TG isn't burned itself. TG are made up of three fatty acids and one glycerol molecule. Glycerol can be converted to glucose and burned and the fatty acids can be burned individually by cells with mitochondria.

As for (b), I have never heard of fructose being essential for fatty acid metabolism. Fructose is sent to the liver and converted into TG. Ketones and fructose aren't the same thing nor is one a type of the other.

Craig

[coconinoz]

thanks for your message, craig; i appreciate it

re. ketone = fructose here's a couple of links:
http://hyperphysics.phy-astr.gsu.edu/hbase/Organic/sugar.html
http://www.elmhurst.edu/~chm/vchembook/543fructose.html

also, i read somewhere that the breath & urine of people in ketosis smell 'fruity'

the larger picture to frame my 1st post is that i am a practitioner of nature driven metabolism (ndm), which is a foundational aspect of the ecological food chain; my paper on the ecological food chain is still in the works

in the meantime, though, 1 thing that occurred to me is that if you eat raw liver & kidney from pastured (grainless ) or wild animals -- assuming (a) the animals you eat are ketone adapted or (b) for some other reason ketones are found especially in the raw liver -- you may reap the following benefits:
~ ketones for your brain, nervous system, blood cells to use as fuel
~ a type of dietary carb (from liver & kidney) to help start the process of complete oxidation of fatty acids, thus satisfying the liver & avoiding bg cascades
~ no need to worry about how to make the oxidation of fatty acids incomplete, which is what would otherwise be needed to produce ketones in the liver (& by the same token not completely satisfy the liver)
~ the liver, which uses fatty acids for fuel, would be completely happy only with the complete oxidation of fatty acids; it would appear, as well, that the liver has to be enticed with its favorite candy: either dietary fructose or dietary ketone
~ you have ketones for your fast twitch muscle fibers (weight training & sprinting) as well as fatty acids for your slow twitch muscle fibers (endurance)

the frequency of daily meals may also affect the degree of completeness of the fatty acid oxidation

needless to say, the point of fully enjoying the above benefits, or any other, is reached only after going through a phase transition (carb driven > lipid driven metabolism or high plant > high raf)
in chaos theory terms, a phase transition appears random, meaningless, unpredictable, non-symmetric to the surface level observer; to the keen observer living an ever fresh life, however, the countless iterations & oscillations gradually reveal an attractor or paradigm: the individual's personal archetype (self similarity)

[Raw Kyle]

you have ketones for your fast twitch muscle fibers (weight training & sprinting) as well as fatty acids for your slow twitch muscle fibers (endurance)

This flies in the face of what I've been reading on here. I was under the impression ketones were what drives the ketogenically adapted long term aerobic metabolism and that glucose or fatty acids is what drives short bursts anaerobic metabolism best.

[coconinoz]

i tend to think that when we transition to our optimal (self-similarity) ketone adaptation we are -- possibly, presumably, hypothetically -- headed in this direction:
skeletal muscles mimic the heart in the sense that they become able to use all 4 kinds of fuels (glycogen, ketones, ffa's, aminoacids)

the posts that follow contain some piecemeal info

[coconinoz]

http://jap.physiology.org/cgi/reprint/96/1/3
"because skeletal muscle glycogen provides the caloric source for high-intensity anaerobic activities, we [the 2 authors] speculate that muscle glycogen storage may have been related to survival during evolution. this notion is supported by the observation of a preferential complete repletion of glycogen in highly oxidative skeletal muscle that occurs in 1-2 hr postexercise in the fed state, which is well before the repletion of liver stores (<50% repletion at 4 hr postexercise) following an exercise bout that depletes muscle & liver glycogen' (p.4).
"type i [slow twitch] skeletal muscle fibers are more efficient than type ii [fast twitch] muscle fibers, because the former uses approximately 1/2 the quantity of atp per unit of work ...
"for decades, dogmas in exercise physiology have been that the major metabolic consequences of the adaptations of muscle to endurance exercise are the slower utilization of muscle glycogen & blood glucose, the greater reliance of fat oxidation & less lactate production during exercise of a given intensity. these interrelated metabolic adaptations to endurance training have been concluded to be largely responsible for the increased aerobic endurance in the trained state, but are also consistent with a more efficient usage of limited muscle glycogen stores as 'thrifty' genes. hence, it is reasonable to speculate that perhaps some adaptations to physical activity-rest may require a cycling of muscle glycogen stores ...
"karlsson & saltin found that manipulation of muscle glycogen levels by diet altered the time of moderate exercise to exhaustion (low carb lowered both the recovery of muscle glycogen levels as well as endurance) ... thus the inherited genes allowing greater fat oxidation lowers the rate of muscle glycogen usage, thereby sparing muscle glycogen stores ...
"interestingly, endurance alters gene expression related to the function of carb sparing in trained individuals. in other words, skeletal muscle preferentially oxidizes ffa's while conserving glycogen during the same absolute workload after training by increasing enzymes involved in b-oxidation of ffa's compared with before training" (p.5).
"a theme common to feast-famine & to physical activity-rest is the cycling of glycogen & tg storage & oxidation. during feast, glycogen storage, tg synthesis & carb oxidation would predominate, whereas in the fasting state glycogen conservation, gng & ffa oxidation would occur. in analogous manner to feast, after physical activity, glycogen & tg resynthesis is a priority, whereas during exercise glycogen sparing & higher ffa oxidation occur in endurance trained skeletal muscle (analogous to fasting) compared with nontrained muscle at the same absolute workload ... many of the metabolic changes associated with physical activity-rest cycles, except for insulin sensitivity, are a mimic of the biochemical changes occurring in the feast-famine cycles ... the cycling by feast-famine & physical activity-res triggers cycling of the storage levels of glycogen a7 tg, which in turn triggers cycling of other metabolic paths" (p.6).

[coconinoz]

http://www.appliedhealth.com/nutri/page17182.php
"Endurance training significantly increases muscle cell oxidative capacity and mitochondrial enzymes. Furthermore, electron microscopy studies have shown both the number and size of the mitochondria increase with endurance training. Mitochondrial enzyme content is also affected by endurance training. Increased levels of enzymes responsible for ketone, fatty acid, NADH and succinate oxidation occur after endurance training. Muscle homogenate and isolated mitochondrial studies document that endurance training increases a muscle's ability to oxidize fatty acids, ketones, and pyruvate.
"Resistance training may decrease mitochondrial volume density in muscle. These changes, however, reflect increases in myofibril volume, whereas mitochondrial volume appears to remain unchanged.
"With endurance training, the myoglobin content of muscle can increase by as much as 80%. These changes increase the amount of oxygen in a muscle cell and facilitate mitochondrial diffusion. Eased diffusion is consistent with a muscle cell's increased oxidative capabilities.
"Typically, humans have about 50% type I (slow-twitch) fibers and 50% type II (fast-twitch) skeletal muscle fibers. While sprinters tend to have a higher percentage of type II fibers and endurance athletes a higher percentage of type I fibers, these differences are likely genetically determined predisposing an athlete to one or the other sporting conditions. Conversion of type II fibers to type I fibers because of exercise training has not been shown to happen, but, conversion of IIb (fast-twitch white, glycolytic) to IIa (fast-twitch red, oxidative) can happen with endurance training. Some forms of endurance training can produce complete conversion of type IIb fibers to type IIa fibers, and the adaptive increases in oxidative capacity appear greater in the type II fibers than in the type I fibers.
"Resistance training appears to selectively increase type I fiber areas faster than type II fiber areas. Furthermore, resistance athlete specialists appear to have differences in fiber type composition. For example, world class body builders, who utilize high volume low intensity resistance programs, have a relatively greater number of type II fibers than Olympic and Power lifters. These differences, however, may also be related to genetic factors."

[coconinoz]

http://alanaragon.com/myths-under-the-microscope-the-fat-burning-zone-fasted-cardio.html

Myths Under The Microscope Part 1: The Low Intensity Fat Burning Zone
By Alan Aragon  © 2006

The “Fat Burning Zone” On Trial
Origin of the myth
"Dietary variables aside, the body’s proportional use of fat for fuel during exercise is dependent upon training intensity. The lower the intensity, the greater the proportion of stored fat is used for fuel. The higher the intensity, the greater proportional use of glycogen and/or the phosphagen system. But this is where the misunderstanding begins. Although I’m burning a greater proportion of stored fat typing this sentence, getting up & sprinting would have a greater impact on [body] fat reduction despite its lesser proportional use of fat to power the increased intensity. Alas, sufficient investigation of the intensity threshold of maximal net fat oxidation has been done. In what’s perhaps the best designed trial of its kind, Achten & Jeukendrup found peak fat oxidation to occur during exercise at 63% VO2 max. This peak level got progressively less beyond that point, & was minimal at 82% VO2 max, near the lactate threshold of 87% [1].

Misunderstanding is perpetuated in fitness circles
"It has been widely misconstrued that a greater net amount of fat is burned through lower to moderate intensity work, regardless of study duration & endpoints assessed. In addition the confusion of net fat oxidation with proportional fat oxidation, the postexercise period is critically overlooked. No distinction is ever made between during-exercise fat oxidation, recovery period fat oxidation, total fat oxidation by the end of a 24-hr period, & most importantly, a longer term of several weeks.. Thus, the superiority of lower intensity cardio continues to be touted over the more rigorous stuff that takes half the time to do. Fortunately, we have enough research data to gain a clear understanding. Let’s dig in."

[coconinoz]

http://www3.interscience.wiley.com/journal/120069519/abstract?CRETRY=1&SRETRY=0
Enzymes Involved in Ketone Utilization in Different Types of Muscle: Adaptation to Exercise
William W. WINDER 1 , John O. HOLLOSZY 1 Kenneth M. BALDWIN 1
1 Department of Preventive Medicine, Washington University School of Medicine, 4566 Scott Avenue, St. Louis, Missouri, U.S.A. 63110
Department of Physiology, University of California, Irvine, California, U.S.A. 92664

ABSTRACT
"Activity levels of the enzymes involved in ketone utilization were compared in heart, fast-twitch red, slow-twitch red, & fast-twitch white types of muscles in rats. 3-Hydroxybutyrate dehydrogenase, 3-ketoacid CoA-transferase, & acetoacetyl-CoA thiolase activities were lowest in white muscle, higher in slow red than in fast red muscle, & highest in the heart. The large differences between the four muscle types in the levels of these enzymes reflects differences in both mitochondrial content & composition. Differences in composition were evidenced by large dissimilarities between the different muscle types in the ratios of the activities of the enzymes of ketone oxidation to each other & to citrate synthase & cytochrome c. Of particular interest is the finding that, despite the fact that in the rat slow red muscle has a lower content of mitochondria than fast red muscle, 3-hydroxybutyrate dehydrogenase activity is 140% higher & 3-ketoacid CoA-transferase is 70% higher in slow red than in fast red muscle.
"A 14-week-long program of treadmill running induced increases in the levels of ketone utilization enzymes in all three types of skeletal muscle but not in heart; 3-hydroxybutyrate dehydrogenase became measurable, though at very low levels, in white muscle; increased 2.6-fold in slow red muscle, & 6-fold in fast red muscle. 3-Ketoacid CoA-transferase increased 2-fold in both fast red & white types of muscle, but only 26% in slow red muscle. Acetoacetyl-CoA thiolase activity increased 40–45% in all three types of skeletal muscle. In contrast, citrate synthase & cytochrome c increased approximately 2-fold in all three types of skeletal muscle. These adaptive changes tend to make skeletal muscles more like heart muscle in their enzyme patterns & may help to explain why physically trained, as compared to untrained, individuals do not develop post-exercise ketosis."
(Received March 30/June 15, 1974)

in my current understanding, the above could mean:
~ the rats were 1st using their muscle glycogen
~ ketone adaptation, ketones are used & thus not eliminated in the urine, is not merely a result of foodstyle but also of exercise (see article on thrift genes by chakravarty)

[coconinoz]

http://www.diabetes.ca/files/Riddell--Final.pdf
"The increased metabolic demand of exercise requires a dramatic increase in fuel mobilization from sites of storage & an increase in fuel oxidation within the working muscle. Normally, the increase in fuel mobilization for oxidation is under neuroendocrine control. During the transition from rest to exercise, the working muscles shift from using predominantly free ffa's released from adipose tissue to a complex mixture of circulating fats, muscle triglycerides (TG), muscle glycogen & bg derived from liver glycogen.
"During the initial stages of exercise, muscle glycogen is the main source of energy, but the reliance on this limited fuel source decreases as the duration of exercise increases. As a result, contributions from circulating free ffa's & glucose in the blood stream increase to replace diminishing muscle glycogen stores. This greater reliance on liver glycogen can have dramatic effects on bg levels. The mixture of fuel utilization differs markedly depending on the intensity of exercise. During low to moderate intensities, plasma-derived free ffa's make up the majority of oxidized substrate. As the intensity increases, there is a greater reliance on carbohydrates. During heavy exercise,bg utilization may be as great as 1 to 1.5 g/min & this fuel source must be continuously replaced at an equal rate or hypoglycemia will ensue (2). The mix of fuel utilization during exercise in people with type 1 diabetes appears to be similar to that of people without diabetes, except that individuals with diabetes may have a slightly greater reliance on fat as an energy source & a slightly lower rate of carbohydrate oxidation (3,4). To facilitate the changes in glucose delivery during exercise, pancreatic insulin secretion decreases & circulating levels of glucagon, growth hormone, cortisol & catecholamines increase. The primary role of these hormonal changes is to ensure an adequate supply of glucose for the exercising muscles (Figure 1A). Usually, the magnitude of change in these hormones is greater with increasing exercise duration & intensity. That is, during prolonged heavy aerobic exercise (i.e.exercising for over 30 min at 60 to 80% of VO2max), the reduction in insulin secretion is more pronounced, while the release of the other glucose counterregulatory hormones is increased to a greater extent ...
"High-intensity exercise may be defined as activities above the 'lactate threshold' which is approximately >60 to 70% VO2max or 85 to 90% maximal heart rate. This threshold coincides with dramatic elevations in catecholamines, free ffa's & ketone bodies, all of which impair muscle glucose utilization."

[coconinoz]

http://www.unisanet.unisa.edu.au/08366/h&p2fat.htm
ß-oxidation of fatty acids
"This is a cyclic series of reactions (occurring within the mitochondria) with the end result of two carbon units being hydrolysed from the ffa chain with each cycle. These two carbon units are molecules of acetyl CoA ...
"These events occur in liver & muscle. During sustained exercise the cells of slow twitch muscle fibres (which possess mitochondria) utilise ß-oxidation as the major source of ATP ...
Ketone bodies
"An alternative method of utilising the acetyl CoA formed by ß-oxidation is via the synthesis & subsequent oxidation of four-carbon units known collectively as ketone bodies.
"Acetyl CoA is converted in the liver into acetoacetate (essentially two acetyl groups covalently linked). Acetoacetate can be further reduced to form ß-hydroxybutyrate. These two compounds are referred to as ketone bodies. Their synthesis occurs in the liver.
"They diffuse from the liver into the circulation & are used as fuels by several tissues. Heart muscle & renal cortex, in particular, use acetoacetate in preference to glucose. In contrast, glucose is the major fuel for the brain & erythrocytes in a human on a balanced diet. The brain has the capacity to adapt to the use of acetoacetate during starvation (and in the metabolic disease diabetes mellitus). In starvation of long standing, acetoacetate meets more than 70% of the energy needs of the brain.
"This ability of the brain to adapt to the use of acetoacetate is important because ffa's cannot enter neural tissue. Acetoacetate is regarded as a water soluble & readily transported form of acetyl CoA.
"The efficiency (amount of ATP produced) of oxidation of ffa's directly or via formation of ketone bodies is approximately the same - there is no penalty to the body in converting acetyl CoA to this water soluble form.
It is important to be aware that there is no mechanism in animals for the conversion of ffa's to glucose."

[coconinoz]

http://avidityfitness.net/2008/05/28/feature-exploding-fat-loss-myths-by-jamie-hale/

"Jamie Hale-Claim: To remove bodyfat you need to use it as fuel. The muscle fibers that are fueled by fat (’slow twitch’ fibers) are the ones that produce easy movements.
"Jamie Hale-Status: You don’t have to learn how to use fuel. Are you aware that you are burning fuel 24 hours per day? When you are sitting doing absolutely nothing you are burning fuel. Many tissues can use free fatty acids for fuel not just slow twitch muscle fibers. Losing bodyfat relies on way more than activity of the slow twitch muscle fibers (how about cal deficit).
"To use slow twitch muscle fibers nervous stimulation is required (CNS requires cals although not fat calories). High intensity exercise often results in a lower RQ (indicating higher proportion of fat) than low intensity exercise post-workout.
"Below is a brief description of what occurs during mobilization of stored fat and oxidation of fatty acids: The following is an excerpt from Fat Burning How it Works by Jamie Hale. I added a few additional comments to make the information more precise.
- Bodies 2 major stores of fat that provide energy 1) adipose tissue 2) intramuscular triglyceride (IMTG)
- Adipose tissue stores fat in the form of triglyceride (triacylglycerols). TG is composed of a glycerol backbone with three FFA attached to it.
- IMTG are droplets of fat stored within the muscle fiber.
- IMTG are contained within the muscle and can be used directly, FFA from adipose tissue must be carried through the bloodstream to the muscles to be used for energy.
- Fats are broken down to fatty acids and glycerol. Glycerol enters the glycolytic/glucogenic pathway via glyceraldehyde 3 phosphate (can be used to from TAG in liver as well). The free fatty acids move through the cell membrane of adipocyte, and bind to albumin in plasma. They are then transported to tissue where they enter cells. Keep in mind regardless of FFA blood levels the brain (although the brain can use ketone bodies) and erythocytes cannot use free fatty acids for energy. Breakdown of TG is initiated by HSL (hormone sensitive lipase), which is primarily influenced by insulin, and the catecholamines. HSL removes a fatty acid from carbon 1 and or 3 of TAG. Additional lipases including Diacyclglycerol and Monoacylglycerol remove the remaining fatty acids (Harvey & Champe 2005).
"Adrenaline and nor adrenaline bind to beta-adrenergic receptors in fat cells stimulating HSL causing FFA release
"FFA is burned in the mitochondria to produce ATP and acetyl-CoA ...
"Each kind of muscle fiber has a preferred fuel system. Slow twitch fibers are more oxygen based and endurance driven. The lower level of intensity the more you are using your slow twitch muscle fibers. Slow twitch provide more energy per unit of fuel and allowing the use of multiple types of fuel (fats, lactate, glucose). Mostly though ffa's are the energy source for slow twitch muscle fibers.
"In the fast twitch fibers the reverse is true, with little to no oxygen and glycogen (stored carbohydrates) being the main source of fuel.
"So in short, walking uses fat as fuel, fast running uses more glycogen (stored carbs) as fuel.
"Now the claim is since this is the case, doesn’t this mean that we should only worry about training in a slow twitch zone if fat loss is the goal?
"This is the common myth that Jamie is, very technically, debunking ...
"Ideally fast and slow twitch muscle work off of a preferred fuel source but, in the end, the body is going to take what it needs from where it can get it."

[coconinoz]

http://www.ncbi.nlm.nih.gov/pubmed/11247746

Enzyme activities support the use of liver lipid-derived ketone bodies as aerobic fuels in muscle tissues of active sharks
2001
Watson RR, Dickson KA.
Department of Biological Science, California State University-Fullerton, Fullerton, CA 92834, USA

"Few data exist to test the hypothesis that elasmobranchs utilize ketone bodies rather than fatty acids for aerobic metabolism in muscle, especially in continuously swimming, pelagic sharks, which are expected to be more reliant on lipid fuel stores during periods between feeding bouts and due to their high aerobic metabolic rates. Therefore, to provide support for this hypothesis, biochemical indices of lipid metabolism were measured in the slow-twitch, oxidative (red) myotomal muscle, heart, and liver of several active shark species, including the endothermic shortfin mako, Isurus oxyrinchus. Tissues were assayed spectrophotometrically for indicator enzymes of fatty acid oxidation (3-hydroxy-o-acyl-CoA dehydrogenase), ketone-body catabolism (3-oxoacid-CoA transferase), and ketogenesis (hydroxy-methylglutaryl-CoA synthase). Red muscle and heart had high capacities for ketone utilization, low capacities for fatty acid oxidation, and undetectable levels of ketogenic enzymes. Liver demonstrated undetectable activities of ketone catabolic enzymes but high capacities for fatty acid oxidation and ketogenesis. Serum concentrations of the ketone beta-hydroxybutyrate varied interspecifically (means of 0.128-0.978 micromol mL(-1)) but were higher than levels previously reported for teleosts. These results are consistent with the hypothesis that aerobic metabolism in muscle tissue of active sharks utilizes ketone bodies, and not fatty acids, derived from liver lipid stores."

[avalon]

Okay, I read a lot of the above, but I got a little winded 

The thought that popped into my head about the liver and kidney is- Is there a big difference between eating fresh liver and kidney from a recent kill or organs that have been packed and cooled and shipped? I mean talking fructose and ketones wise and stuff...

[xylothrill]

I'm still trying to get past the ketone/fructose and dietary ketone thing. That really throws a money-wrench into the works. Good work here!

Craig

[coconinoz]

"... a monkey wrench in the works..."

this  is totally cryptic to me -- been thinking about it for a whole week & still cannot figure it out, at all

indeed, i'm eager to see a complete list of all the problems, errors, mistakes, misunderstandings, misconceptions, inconsistencies, gaps...etc etc in what i wrote

let's look at the devil in the eye!
craig & all: please shine your light!
(this is an educational board, no?)

looking forward to it

thanks