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Offline Lo.Lee.Ta.

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Trying to understand the possible states of metabolism...
« on: April 09, 2015, 09:50:43 PM »
I will probably have to post multiple times on this thread to fully figure things out! :/
I am in biochem right now and am really trying to understand metabolism intuitively- even though a deep understanding is not really required for the course...

Ultimately, I'd like to look at real life situations and see what biochemical pathways are used.
First, though, I want to make sure I even have the basics correct! :/

Possible states I want to analyze:

1. Losing weight: Expending more calories than taking in

   *balanced diet  vs.  *no carb diet  vs.  *high carb diet  vs.  *complete fasting


2. Gaining weight: Taking in more calories than expending

   *balanced diet  vs.  *no carb diet  vs.  *high carb diet 


3. Maintaining weight: Taking in same amount of calories as expending

   *balanced diet  vs.  *no carb diet  vs. *high carb diet



Isn't it true that all weight loss, gain, or maintenance boils down to just the number of calories used versus the number of calories eaten?
I don't understand, then, why a low carb diet is said to be optimal for losing weight. There would be a decrease in insulin, the hormone that signals the body to store fat rather than break it down...But what if the same number of calories that used to be ingested from carbs were just replaced with calories from fat and protein?
Assuming a person had to eat 2000 calories to maintain their weight, it wouldn't matter if the 2000 calories were achieved by consuming a balanced diet, a low carb diet, or a high carb diet, would it? The person would not lose weight unless total calories were less than 2000, right?
Is the only advantage of a low carb diet being that a person should not feel as hungry, since many of the calories are from fat and protein, which do not affect blood sugar levels nearly as drastically as carbs do?


I want to have the correct general understanding before I try to look at specific biochemical pathways...
Thanks SO much!!!  :)

Offline Yggdrasil

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Re: Trying to understand the possible states of metabolism...
« Reply #1 on: April 10, 2015, 12:45:21 AM »
Isn't it true that all weight loss, gain, or maintenance boils down to just the number of calories used versus the number of calories eaten?

Yes, this is true.

Quote
I don't understand, then, why a low carb diet is said to be optimal for losing weight. There would be a decrease in insulin, the hormone that signals the body to store fat rather than break it down...But what if the same number of calories that used to be ingested from carbs were just replaced with calories from fat and protein?
Assuming a person had to eat 2000 calories to maintain their weight, it wouldn't matter if the 2000 calories were achieved by consuming a balanced diet, a low carb diet, or a high carb diet, would it? The person would not lose weight unless total calories were less than 2000, right?
Is the only advantage of a low carb diet being that a person should not feel as hungry, since many of the calories are from fat and protein, which do not affect blood sugar levels nearly as drastically as carbs do?

Here is where we begin getting into areas that are still under debate.  Some scientists would say, it doesn't really matter (for weight loss at least) what types of calories you eat (all calories are equal) while other might argue that some types of calories are worse than others.  Unfortunately, depending on who you ask, some would say that carbohydrates (especially fructose) are the problem while others would point to fats (especially saturated fats and trans fats) as being the worst culprits. 

Although many try to follow dietary guidelines released by government agencies like the US FDA, many of these guidelines are being revised, and have recently come under criticism.  A recent op/ed column in the New York Times gets at the heart of the problem:

Quote
The primary problem is that nutrition policy has long relied on a very weak kind of science: epidemiological, or “observational,” studies in which researchers follow large groups of people over many years. But even the most rigorous epidemiological studies suffer from a fundamental limitation. At best they can show only association, not causation. Epidemiological data can be used to suggest hypotheses but not to prove them.

Instead of accepting that this evidence was inadequate to give sound advice, strong-willed scientists overstated the significance of their studies.

So, I think most experts are in the same position you are.  We really don't fully understand all that's going on yet.

Offline Furanone

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Re: Trying to understand the possible states of metabolism...
« Reply #2 on: April 10, 2015, 10:25:16 AM »
As someone who works in the food industry (although with limited nutritional science), I can say with quite a lot of confidence that not all calories are digested and absorbed the same into human bodies as they would be determined based on the standard bomb calorimeter testing that shows that fat~9 KCal/g, protein~4 KCal/g, and carbohydrates~4 KCal/g.

If you are really interested in this topic, may I recommend some documentaries that you can watch from YouTube on the topic, and get into the science particularly the biochemistry very well by Dr. Robert Lustig (Sugar: the Bitter Truth), and Dr. Peter Attia on low-carb diets where nutritional ketosis is successfully sustained over years.

When the McGovern report came out in the late 1970s, it indicted fats (particularly saturated fats) as the enemy leading to all the symptoms typical of metabolic syndrome (obesity, high blood pressure, insulin resistance, cardovascular disease, high blood triglycerides & high LDL 'bad' cholesterol while lowering HDL 'good' cholesterol). This was based on flawed epidemiological studies of different countries health stats. Since then, the food industry has gone on a craze for lowering fat content in food, while filling this void with the much cheaper ingredient of refined sugars/HFCS (third cheapest ingredient after air and water!) -- and guess what -- people have not gotten healthier since then, but more obese and Type-II diabetes is skyrocketing out of control. Lustig shows the metabolic pathways of how sugars are digested and where with glucose only about 20% makes it to the liver for processing (as other organs and muscle tissue consume 80% for their energy needs), while 100% of fructose (the other monosaccharide half of the disaccharide sucrose) makes it to the liver where it is preferentially processed into fat (adipose & liver fat) through different enzymatic pathways, while glucose is more preferentially stored as glycogen. He quite convincingly argues that not all calories are the same. Many doctors have reported that diabetics who have gone on very-low carb diets (<20 g/day) with a high fat & protein diet have lost weight, and in some cases no longer require taking insulin. Also, it has been prescribed to epileptics as it has had a very positive effect on eliminating their seizures.

https://www.youtube.com/watch?v=dBnniua6-oM
https://www.youtube.com/watch?v=wM2W_zEp5kk
http://www.nytimes.com/2011/04/17/magazine/mag-17Sugar-t.html?_r=2&pagewanted=all

Dr. Peter Attia has lived on very low carbs since 2009 and has performed many experiments on himself, where he has spent many days in a metabolic chamber where the net volume of oxygen going in and net volume of carbon dioxide going out are measured, and additionally blood glucose & ketone levels were monitored (as well as other markers, etc.). Knowing the vO2 & vCO2 can very accurately calculate the calories expended and if they are burned from fat (low vO2/vCO2 ratio ~0.7-0.8 ) vs calories burned from carbohydrates (high vO2/vCO2 ratio ~0.9-1.0). It showed even at night during sleep he was burning about 20% more calories based on living in a state of ketosis suggesting there is a higher energy cost for converting fats to ketones and using as energy than sugars for energy.

https://www.youtube.com/watch?v=NqwvcrA7oe8
http://eatingacademy.com/

Very interesting indeed. I'd like to hear your thoughts on them, if you do have the chance to watch some of these documentaries. As for your comments about people losing weight on the low carb diet due to fat & protein giving a greater feeling of satiety and suppressing appetite, this is for sure part of the debate. It is known that fats pass through our stomachs  into intestines slowest while carbs pass through our stomachs fastest and stimulate insulin the most which is closely-related to leptin (the 'starvation' hormone). Some argue that insulin-resistance also results in leptin-resistance, meaning a high carb diet will result in not feeling full. I think there may be a bit of both -- lower appetite from eating fats & proteins as well as a higher energy expenditure when the fat-burning/ketosis metabolic pathway is favoured over energy expenditure based on burning carbs. This is an exciting area of research and I believe a large amount relating to this topic will be elucidated in the next few years, and then us food scientists will have to start replacing the added sugars in the foods with added fat!




« Last Edit: April 10, 2015, 11:40:09 AM by Furanone »
"The true worth of an experimenter consists in pursuing not only what he seeks in his experiment, but also what he did not seek."

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Offline Corribus

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Re: Trying to understand the possible states of metabolism...
« Reply #3 on: April 10, 2015, 12:49:39 PM »
@Furanone, regarding the recommended documentaries:

I have to question anyone who is willing to call fructose a "poison".  The use of such provocative language is disingenuous and makes me question Dr. Lustig's motives. Certainly, ingesting huge amounts of refined sugar is probably not good for anyone, but as science professionals we have a duty to communicate scientific facts to laypeople in an honest, straightforward way. Intentionally misleading people or manufacturing controversy through the use of hyperboly, euphemisms, or other forms of chicanery is both unprofessional and unethical.
What men are poets who can speak of Jupiter if he were like a man, but if he is an immense spinning sphere of methane and ammonia must be silent?  - Richard P. Feynman

Offline Furanone

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Re: Trying to understand the possible states of metabolism...
« Reply #4 on: April 10, 2015, 12:58:34 PM »
@Furanone, regarding the recommended documentaries:

I have to question anyone who is willing to call fructose a "poison".  The use of such provocative language is disingenuous and makes me question Dr. Lustig's motives. Certainly, ingesting huge amounts of refined sugar is probably not good for anyone, but as science professionals we have a duty to communicate scientific facts to laypeople in an honest, straightforward way. Intentionally misleading people or manufacturing controversy through the use of hyperboly, euphemisms, or other forms of chicanery is both unprofessional and unethical.

I agree wholeheartedly with what you are saying -- the philosophy of letting the facts/science speak for itself. The NY Times article link I provide above by Gary Taubes also discusses & questions the strong (emotional) language that Lustig chooses to convey his point, and writes that Lustig has intentionally chosen such a style of delivery since nothing is being done about it, and that Lustig himself has been quoted before as saying it must also be the role of the researcher who has made certain discoveries to also advocate for the policy changes that these findings suggest should be made, since this cannot be trusted by the industry to self-police who have a financial stake in maintaining the status quo, or by the government agencies due to pressures from the industry.

Lustig says he believes the only way to affect change on this scale, as with cigarettes or another example he uses is seat belts in cars, is with a bottom-up model (ie grass-roots public pressure) as the past has shown a top-down model (drastic government reform) rarely happens, so in his opinion strong language helps to achieve this. I guess he is part politician in addition to a scientist.
« Last Edit: April 10, 2015, 01:12:22 PM by Furanone »
"The true worth of an experimenter consists in pursuing not only what he seeks in his experiment, but also what he did not seek."

--Sir William Bragg (1862 - 1942)

Offline Yggdrasil

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Re: Trying to understand the possible states of metabolism...
« Reply #5 on: April 10, 2015, 01:16:00 PM »
Although I tend to agree with Lustig et al., it's worth noting that not everyone agrees with the thought that sugars is the main culprit behind current trends in obesity (for example, see http://wholehealthsource.blogspot.com/2011/08/carbohydrate-hypothesis-of-obesity.html).  The post does not address some of the more recent studies of the role of fructose in liver metabolism, but he does make some good points, nonetheless.

Offline Corribus

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Re: Trying to understand the possible states of metabolism...
« Reply #6 on: April 10, 2015, 02:03:45 PM »
Lustig says he believes the only way to affect change on this scale, as with cigarettes or another example he uses is seat belts in cars, is with a bottom-up model (ie grass-roots public pressure) as the past has shown a top-down model (drastic government reform) rarely happens, so in his opinion strong language helps to achieve this. I guess he is part politician in addition to a scientist.
I understand the approach, but disagree with the philosophy that the ends justify the means because of the potential for collateral damage. With such a low level of scientific literacy in this country, scientists should be a source of good information, reason, and facts. Here's an example of why: suppose you are able to effect this kind of downstream change by convincing people that fructose is a poison. Well and good. At the same time, you engender mistrust between the public and the food industry and create a false controversy among scientific professionals. This reduction in trust puts in jeopardy other emerging product technologies that may be beneficial but are in a delicate area of public perception, such as GMO, irradiation, nanoscience, etc. These technologies should be judged on their own terms, rather than endangered due to guilt by association.

Well, that's just my opinion. Sorry to derail the thread - the interaction between scientists and the public is a subject I'm passionate about. :)
What men are poets who can speak of Jupiter if he were like a man, but if he is an immense spinning sphere of methane and ammonia must be silent?  - Richard P. Feynman

Offline Furanone

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Re: Trying to understand the possible states of metabolism...
« Reply #7 on: April 10, 2015, 03:25:04 PM »
Although I tend to agree with Lustig et al., it's worth noting that not everyone agrees with the thought that sugars is the main culprit behind current trends in obesity (for example, see http://wholehealthsource.blogspot.com/2011/08/carbohydrate-hypothesis-of-obesity.html).  The post does not address some of the more recent studies of the role of fructose in liver metabolism, but he does make some good points, nonetheless.

Thanks for link -- this was an interesting read. He offers many examples of situations of non-western cultures where carbs are a high percentage of the caloric intake from the diet yet obesity or diabetes is not common. However, I still think much of what he writes can still fit in with the western diet since the late 1970s adding in so much unnecessary sugar to processed foods making them overly nutrient dense thus leading to metabolic overload in the liver resulting in fatty liver and insulin resistance and ultimately metabolic disorder. I agree insulin is not the enemy, but insulin resistance (and likely leptin resistance). He does acknowledge a low carb, high fat/protein diet can lead to substantial weight-loss in obese individuals, but I wish he got into this in greater detail.
"The true worth of an experimenter consists in pursuing not only what he seeks in his experiment, but also what he did not seek."

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Offline Furanone

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Re: Trying to understand the possible states of metabolism...
« Reply #8 on: April 10, 2015, 03:46:12 PM »
Lustig says he believes the only way to affect change on this scale, as with cigarettes or another example he uses is seat belts in cars, is with a bottom-up model (ie grass-roots public pressure) as the past has shown a top-down model (drastic government reform) rarely happens, so in his opinion strong language helps to achieve this. I guess he is part politician in addition to a scientist.
I understand the approach, but disagree with the philosophy that the ends justify the means because of the potential for collateral damage. With such a low level of scientific literacy in this country, scientists should be a source of good information, reason, and facts. Here's an example of why: suppose you are able to effect this kind of downstream change by convincing people that fructose is a poison. Well and good. At the same time, you engender mistrust between the public and the food industry and create a false controversy among scientific professionals. This reduction in trust puts in jeopardy other emerging product technologies that may be beneficial but are in a delicate area of public perception, such as GMO, irradiation, nanoscience, etc. These technologies should be judged on their own terms, rather than endangered due to guilt by association.

Well, that's just my opinion. Sorry to derail the thread - the interaction between scientists and the public is a subject I'm passionate about. :)

I agree, especially when the less science-educated public is always getting confused over the terminology and especially the contradictions in science when new discoveries are made that conflict with older models. Just some examples where the public get confused is with cholesterol first being bad, then there was good vs bad cholesterol (HDL vs LDL), and now there is bad LDL vs good LDL (small dense LDL articles vs larger buoyant LDL particles) -- Or try explaining glucose, fructose and sucrose, lactose and how starch are chains of glucose and their different effects on glycemic index to a layperson and how confused they will initially get until they become more educated on the topic.

However, even though Lustig has chose to use his strongly-worded, emotionally-inflammatory language whether it be to try to incite enough public rage to affect some bottom-up policy change or whether he is doing it to get media attention to promote his career, the science from world-leading researchers he is presenting is still very good, and I would trust his non-industry affiliated message (however flamboyant it may be) over the many industry-sponsored scientific studies that emerge and show a diminished effect promoting status quo. I would argue these will do far more to promote confusion and distrust within the less scientific general public.
"The true worth of an experimenter consists in pursuing not only what he seeks in his experiment, but also what he did not seek."

--Sir William Bragg (1862 - 1942)

Offline Lo.Lee.Ta.

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Re: Trying to understand the possible states of metabolism...
« Reply #9 on: April 10, 2015, 05:14:11 PM »
Oh, wow! I didn't realize there was so much debate as to the usefulness of one diet over another.
It's good to know that calorie intake versus expenditure is GENERALLY the mechanism by which weight is either maintained, lost, or gained, regardless of where the calories came from.

When I become more advanced, I'd like to look at these different theories more in-depth! ha :)


When carbs are eaten, the first step is absorption.

Carbohydrate Absorption steps:

1. Carbs are mostly broken down in the small intestine and become the monosaccharides:  glucose, fructose, and galactose. Only these carbs can be absorbed by the small intestine villi.


       *(I see only these 3 monosaccharides listed when I look up types of monosaccharides humans absorb… But aren’t there more? Like glycerol- that’s a monosaccharide too, right?)

       *(It doesn’t matter if we happen to have eaten alpha-glucose MONOMERS or beta-glucose MONOMERS, does it? Because these can just interconvert, right?
The only reason they say only alpha-glucose is digestible is
because they are really talking about alpha-glucose LINKED to other alpha-glucoses, right? Only the alpha(1,4) glycosidic bonds in polymers can be broken (like in starch), and not the beta(1,4) glycosidic bonds (like in cellulose).
So, it’s not a matter of the alpha or beta glucose monomer, itself, being digestable- because BOTH of them are. It’s only that humans can’t access the beta glucose monomer because there is no enzyme to break beta(1,4) glycosidic linkages? …Is this right…? :/
               
2. Once the monosaccharides pass into the villi cells by secondary active transport, they leave on the other side of the villi cells through the GLUT 2 transporter. The GLUT 2 transporter only uses facilitated diffusion to let the monosaccharides into the interstitial fluid. From the interstitial fluid, only diffusion allows the sugar into capillaries.


       *(So, the monosaccharides are trapped inside the villi cells because active transport was used. So there will always be uptake of sugar into the villi no matter how concentrated it is in there? There does exist a sugar equilibrium between the interstitial fluid and the villi cells, since facilitated diffusion is used, right? For instance, if a person has a high blood sugar, it would be just as sugary inside of the villi cells as in the interstitial fluid as in the capillaries, right?         


Is my understanding right so far...? Thanks! :)

Offline Babcock_Hall

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Re: Trying to understand the possible states of metabolism...
« Reply #10 on: April 11, 2015, 09:42:57 AM »
Glycerol is more reduced (by two electrons) than dihydroxyacetone or glyceraldehyde (the latter two have the same oxidation state as glucose).  It looked to me as if everything you said about alpha and beta linkages was correct.  Active transport can move things only so much as its energetics will allow.  IIRC two sodium ions are moved per glucose, and of course the Na+/ K+ ATPase pumps the sodium ions back out.

Offline Yggdrasil

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Re: Trying to understand the possible states of metabolism...
« Reply #11 on: April 11, 2015, 11:48:28 PM »
1. Carbs are mostly broken down in the small intestine and become the monosaccharides:  glucose, fructose, and galactose. Only these carbs can be absorbed by the small intestine villi.

Carbohydrate digestion actually begins in the mouth where salivary amylase begins breaking starches down into glucose.  I have no idea where the bulk of starch breakdown occurs, however.

Offline Lo.Lee.Ta.

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Re: Trying to understand the possible states of metabolism...
« Reply #12 on: April 12, 2015, 03:41:09 AM »
Steps of monosaccharide metabolism:

1. The monosaccharides circulating in the bloodstream enter cells to undergo cellular respiration.
Glucose requires insulin to enter cells, but fructose and galactose do not.
                  
Questions:

*What if diabetics only ate fructose and galactose-would their blood sugar always be normal? They wouldn't need insulin, then, it seems...
         

*Is glucagon/epinephrine/cortisol required for weight loss?
*The only reason why a person loses weight is because the body has to use its own stored energy reserves to maintain proper blood sugar level, since food intake is not sufficient to maintain blood sugar?
*It seems to me that glucagon, epinephrine, or cortisol would be required for weight loss, because isn't glycogenolysis and subsequently, gluconeogenesis the only thing that causes energy reserves to get used?


*Even though an untreated type 1 diabetic has a high blood sugar, they still undergo glycogenolysis and gluconeogenesis?
*I know they lose a lot of weight- is this so that their normal body cells can get energy from ketone bodies, at least?


*I know the brain has a different type of GLUT receptor that doesn't require insulin, so the brain of an untreated type 1 diabetic is able to utilize glucose?


*Since most normal body cells do need insulin to take up glucose, do they instead have to run off of ketone bodies when insulin is not present?
*If this is the case, wouldn't weight loss in untreated type 1 diabetics actually make their blood sugar go even higher but also be necessary, since their other body cells can't function without ketone bodies for fuel?


*Do type 1 diabetics produce glucagon. It does not seem like they would be able to- otherwise, why is a glucagon injection necessary when their blood sugar goes too low?


*If they don't produce glucagon (even though it's produced by panceatic alpha cells, which should not be affected...), then how does their body know to lose weight and undergo gluconeogenesis?
*Is their weight loss only controlled by epinephrine and cortisol...?


*If an untreated type 1 diabetic were to completely fast, their blood sugar would never decrease to normal, would it?
*Is this because even though the brain uses up glucose, their fat/protein stores are always being broken down into more glucose + ketone bodies (to supply most body cells)?


*Do cells always take up glucose against the concentration gradient?
Is there ever a time when cells are too full of sugar and won't take up any more?

I know I've asked a ton of questions, but I have seriously tried to look up and figure this stuff out forever! I can't seem to find the answers anywhere!

Thanks so much!  :)

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