Digestive system - fat/amino acid transfer and metabolism (liver)

[Monkeymaniac]

Guys, I'm totally stuck here and would really appreciate if you guys can clear up some of the questions I have. It just seems that sometimes you can't find the information you want even after searching through the EK/TPRH/wiki trio .

Regarding the topic, I understand up to the point where ingested fats get absorbed by enterocytes to form chylomicrons, and that these lipoproteins include various kinds of fats like triglycerids, fatty acids, cholesterol, and phospholipid. And also that these get eventually transported to large veins in the neck.

It is stated in TPRH that,

Chylomicrons are degraded by lipases into triglycerids, glycerol, and cholesterol rich chylomicron remnants. These remants are taken up by hepatocytes and combined with proteins to make lipoproteins.

1) Where exactly are these lipases located at? Do they reside inside the hepatocytes? or on surface of them?

2) Do chylomicrons get first dumped into the interstitial fluid between hepatocyes from liver capillaries, taken up by hepatocytes, and then degraded by liproprotein lipases?

3) I understand that fatty acids get oxidized in liver to be used as energy source. Quick look up in wikipedia suggests that this fatty acid degradation is done in both liver and kidney. Why would this occur in the latter, since kidney doesn't even store fats as liver cells do?

It is stated in EK that,

Protein metabolism: The liver deaminates amino acids, forms urea from ammonia in the blood, ...

4) Doesn't deamination of amino acids (conversion of amino acids to citric cycle intermediates) occur in almost every type of cell during starvation? That is, why does the book state as if this is a unique task of liver? Thanks in advance!

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[RogueUnicorn]

First of all, you are getting bogged down by relatively insignficant details. The AAMC doesn't care that you know everything about everything.

1) Where exactly are these lipases located at? Do they reside inside the hepatocytes? or on surface of them?

There are secreted pancreatic lipases as well as membrane associated lipases in peripheral cells.

2) Do chylomicrons get first dumped into the interstitial fluid between hepatocyes from liver capillaries, taken up by hepatocytes, and then degraded by liproprotein lipases?

chylomicra are formed by intestinal cells, not hepatocytes. the liver puts out HDL and VLDL. intestinal enterocytes put out chylomicra that are taken up by the lymphatics, and dumped into the circulation in the thoracic duct. as it so happens, the heart is the first place, essentially, that 'sees' the newly ingested fats and cholesterol. interesting, right?

3) I understand that fatty acids get oxidized in liver to be used as energy source. Quick look up in wikipedia suggests that this fatty acid degradation is done in both liver and kidney. Why would this occur in the latter, since kidney doesn't even store fats as liver cells do?

The purpose of fatty acid catabolism in the liver is not to store them, it's to provide energy in the form of ketone bodies. I have no idea why it occurs in the kidney, but I would assume it's for some metabolic purpose. It's an unimportant detail.

4) Doesn't deamination of amino acids (conversion of amino acids to citric cycle intermediates) occur in almost every type of cell during starvation? That is, why does the book state as if this is a unique task of liver? Thanks in advance!

No, deamination requires specific enzymes not present in most cells. The urea cycle can only be fully completed in the liver, if I know this right. You can't have muscle cells with the ability to break down AAs, or you would have a mess trying to sort out anabolism/catabolism.

 

[docelh]

Most cells are capable of oxidizing fatty acids. Key exceptions include the brain. The triggering of fatty acid catabolism is usually associated with low blood sugar. The liver does use fatty acids to power itself, and to spare what remaining glucose is around and can be synthesized from pyruvate/lactate, glycerol, and amino acids.

It's uncertain to me whether enzymes that de-animate aspartate, asparagine, glutamate, and glutamine are only in the liver. But yeah, regadless, the liver exclusively synthesizes urea.

 

[fizzgig]

intestinal enterocytes put out chylomicra that are taken up by the lymphatics, and dumped into the circulation in the thoracic duct. as it so happens, the heart is the first place, essentially, that 'sees' the newly ingested fats and cholesterol. interesting, right?

i'm gonna try to tack on here before making a new thread...

so the majority of fatstuffs is packaged in chylomicrons, which move into the villi lacteals, and get dumped into circulation in a major vein, which goes to the heart, then systemic circ...

so is it correct that carbs and proteins go to the liver first but fats do not?
EDIT: the reason i ask is that the EK book says fat goes to lacteal to lymphsystem to thoracic duct to large neck veins... but then says " thus the first stop for most of the digested fat is the liver"... mmmrrh?

with regard to first pass effect, would this mean that fat soluble drugs would not be subject to first pass, or would they likely not end up in those micelles that go to the lacteal, being either too big to be absorbed at all or small enough that they just diffuse into the blood stream like really small fatty acids?

 

[Phantastic]

so is it correct that carbs and proteins go to the liver first but fats do not?
EDIT: the reason i ask is that the EK book says fat goes to lacteal to lymphsystem to thoracic duct to large neck veins... but then says " thus the first stop for most of the digested fat is the liver"... mmmrrh?

After the neck veins, I believe it is on its way to the liver, and the liver could be considered its first "stop," even though it takes an indirect route. As for the drugs, I believe they diffuse into the blood stream.

 

[RogueUnicorn]

mid- and short-chain fatty acids freely diffuse into the circulation, which goes through the hepatic portal system immediately following. your lipophilic drugs would be under this category

 

[fizzgig]

phantastic, the only veins that go to liver vs to heart are digestive related organs i thought... do large veins in the neck really go to the liver?? magical wiki says the thoracic duct empties into the left brachiocephalic vein and that merges with some other stuff to form the vena cava...

thanks for the drugs answer as well y'all...

 

[RogueUnicorn]

no the neck veins go straight to heart

 

[Phantastic]

Yea, my bad, I think I always assumed they found their way there eventually do to quotes like the one you pointed out. They must have meant the smaller FA's from digestion.

 

[fizzgig]

i agree. EK says ~80% of digested fatstuffs go through the lacteal/lymphatic/thoracic duct route, then probably mentions that smaller stuff goes directly to the bloodstream, and then says the first stop for "most of the digested fats is the liver". i'm going to assume it's just badly written that way, which as fine now that i think i understand it regardless.