AA Transport & Metabolism (LM 11.1) Flashcards

1
Q

what does nitrogen balance mean?

A

that the total amount of nitrogen in the body is stable over time

aka the body’s input vs. output of nitrogen in nitrogen containing compounds is equal on an ongoing basis

healthy humans are generally in nitrogen balance

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2
Q

what is a large amount of the body’s nitrogen a part of?

A

a large amount of the body’s nitrogen is comprised of nitrogen in AA in proteins

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3
Q

what are the body’s sources of nitrogen?

A
  1. incoming protein (AA) from the diet
  2. normal or pathological protein turnover in tissues
  3. turnover of other nitrogenous compounds such as nucleotides and ammonia produced by gut bacteria
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4
Q

what are the two ways of getting rid of excess nitrogen in the body?

A
  1. urea from the liver

2. ammonium ion by the kidney

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5
Q

how is nitrogen present in the body?

A

ammonia or ammonium

free ammonia or ammonium is actually very toxic so the body takes a lot of care to minimize the levels of these

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6
Q

what is the first step in AA catabolism? what happens to what’s left?

A

removal of their alpha-amino group

the remaining carbon skeleton is used in biosynthetic reactions or oxidized to produce energy?

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7
Q

what is protein turnover?

A

the ongoing and equally balanced synthesis and degradation of protein molecules in the body

in a healthy and well-fed adult, the total amount of protein in the body remains constant because the rate of new protein synthesis is just sufficient to replace the constant normal degradation of the body’s protein

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8
Q

is there a storage form of protein in the body?

A

NO

only carbohydrates (glycogen) and fats (TAGs) do

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9
Q

what’s the purpose of proteins in the body?

A

they do work in the body! muscles, structural proteins, enzymes, etc. all do stuff in our body

they aren’t meant to be used as energy unless you’re literally starving

fats and carbs are indeed meant for energy though

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10
Q

what is the body’s amino acid pool?

A

all the various locations and types of “free” AA in the body

the AA pool is also in balance - so what AA get taken out via output sources also get replaces from input sources

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11
Q

what are free amino acids? where are they found?

A

the single, individual AA not incorporated into proteins

they’re ready for the body to grab for bimolecular synthesis pathways at any time

they’re found in the blood, within cells, in the extracellular space

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12
Q

what are the 3 major sources of input into the body’s AA pool?

A
  1. body protein (the synthesis side of protein turnover)
  2. dietary protein (can vary)
  3. synthesis of non-essential AA (if dietary consumption is sufficient, then the body won’t make AA)
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13
Q

what are the major output sources of the body’s AA pool?

A
  1. body protein (protein degradation)
  2. synthesis of: porphyrins, creatine, neurotransmitters, purines, pyrimidines, other nitrogen containing compounds
  3. glucose & glycogen production; ketone bodies, FA & steroid synthesis; CO2 + H2O production from AA not used in biosynthetic reactions being burned as energy (varies based on energy needs)
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14
Q

what type of nitrogen imbalance is concerning? what is it?

A

negative nitrogen balance

it’s not healthy in the longer term because it means that your body is not taking in enough protein to rebuild its needs

examples:

  • long term starvation/anorexia
  • poor nutrient absorption
  • lack of protein in diet
  • other causes of muscle atrophy
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15
Q

what is positive nitrogen balance?

A

generally not an unhealthy condition

examples:

  • body building to increase muscle mass
  • pregnancy
  • growing children
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16
Q

what are examples of people who would be in nitrogen balance?

A
  1. a 19 year old healthy male college student who is self-described couch potato who has been on a reduced far diet, but not low calorie diet, for the last month
  2. a 5 year old child who has had the flu for 1 day but is still eating normally
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17
Q

what are examples of people who would be in negative nitrogen balance?

A
  1. a person in late stage ALS

2. a late stage cancer patient who lost her appetite and is eating very little the last two months

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18
Q

what is the major form for storage of AA in the human body?

A

THERE ISN’T ONE!!

there is NO storage form for amino acids in the body ):

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19
Q

does digestion or absorption happen first?

A

digestion

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20
Q

what is digestion?

A

the process of degrading complete dietary proteins within the lumen of the small intestine

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21
Q

what is absorption?

A

digestion degrades dietary proteins in the lumen of the small intestine

absorption is getting these individual amino acids or di- and tri- peptides into the cells of the small intestine (intestinal enterocytes)

from there they are delivered into the blood stream for uptake into various tissues (primarily the liver)

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22
Q

what are the steps in protein digestion and absorption?

A
  1. pepsin starts the enzymatic action of digestion - secretion of HCl by the stomach also contribute somewhat to the initial breakdown of proteins
  2. enzymes are produced by the pancreas and secreted into the duodenum of the small intestine for protein digestion (trypsin, chymotrypsin, elastase, carboxypeptidase)
  3. most of the protein is now free AA in the intestinal lumen mixed with some oligopeptides –> SI enterocytes have transporters that face the lumen and once oligopeptides are transferred into enterocytes, amino-peptidases and di- & tri- peptidase enzymes convert them to individual AA

**only individual AA can travel in the blood, not oligopeptides or polypeptides

23
Q

what happens when there’s defects in the absorption process of AA in the small intestine?

A

there will be AA in the feces

analysis of feces will tell you which AA are not being well-absorbed and which AA transporters may be defective (usually due to a mutation in the gene for that transporter)

24
Q

what is Hartnup Disease?

A

poor absorption of tryptophan due to mutation in the tryptophan transporter in the enterocytes of SI

25
Q

explain how the hepatic portal system works when it comes to uptake and delivery of amino acids

A
  1. digestion, absorption and release of AA by enterocytes of SI and efflux of single, individual AA into the capillary beds of the SI
  2. individual AA travel via the hepatic portal vein to the liver
  3. liver takes up most types of AA for its own use in hepatocytes aka most incoming dietary AA catabolism occurs in the liver
    - excess AA not needed by the liver continue through the blood stream
  4. remaining AA enter the general circulation via hepatic veins which empty into the inferior vena cava for distribution via blood to other cells and tissues
26
Q

what catabolizes the majority of branched chain amino acids?

A

skeletal muscle!

not the liver because doesn’t have much activity for the specific transaminase that can remove the alpha-amino group from branched chain AA

27
Q

what happens to AA that don’t get taken up by the liver?

A

extra individual AA travel in the blood stream to be taken up into various cells/organs via function of specialized AA transports on cell membranes

most US meals have lots of proteins and carbs to provide stable blood sugar so in the post-prandial state (hours following a meal), the liver doesn’t need to use catabolism of these dietary-derived AA to provide gluconeogenic precursors

so instead these extra AA are provided to other tissues and cells as AA building blocks for the synthesis of new proteins –> this assures that degradation and synthesis of the variety of needed proteins is in a steady state

28
Q

what is the spatial specialization of the cell membrane of enterocytes in the small intestine?

A

enterocytes are a polarized cell type

there are 2 functional regions of enterocytes: apical (luminal) and basolateral surface

AA are absorbed from intestinal lumen across the cell membrane into enterocytes via a variety of specialized AA membrane transporters

AA are released into the blood from enterocytes by a variety of transporters on their basolateral surface

29
Q

what is the apical region of enterocytes? what’s special structure does it have?

A

apical region is also known as the luminal region because this portion of their cell membrane faces the lumen of the small intestine

the lumen is the hollow area “tube” of the intestinal region of the digestive tract where the food that is being digested travels

apical membrane has microvilli which increase surface area for efficient absorption = brush border (looks like a brush!)

30
Q

what is the mechanism of AA transport into and out of enterocytes?

A

AA are polar so they can’t just cross the cell membrane of enterocytes so instead they need secondary and sometimes tertiary transport

you usually need a co-transport of sodium –> Na goes down its gradient into the cell and brings the AA with it against its respective gradient = 2° active transport

Na concentration is higher in the small intestinal lumen due to generally high dietary sodium and the Na/K ATPase at the basolateral surface that’s actively pumping Na out of the cell (1° active transport using ATP hydrolysis)

another type of transporter (PepT1) has a co-transported hydrogen ion that helps bring in oligopeptides into enterocytes - so not only individual AA can come into the cell!

31
Q

how many enterocyte transporters are there?

A

there’s a lot of AA structures and transporters and highly structurally matched to specific material that they’re meant to transport so there’s also a lot of transporters to match the variety of AA (however, structurally related AA can utilize the same transporter)

32
Q

what is the transporter that brings oligopeptides into enterocytes from the lumen?

A

PepT1

once the oligopeptides are inside the enterocyte, they are hydrolyzed into individual AA so that they can be transported into the blood stream

33
Q

what are the 4 types of amino acid transporters at the apical surface that function in absorption of AA?

A
  1. Na+ dependent Imino Transporter
  2. Cationic AAs and Cystine
  3. Na+ dependent neutral AA transporter
  4. Na+ dependent Anionic AA transporter
34
Q

what are the diseases that arise from defective luminal transporters?

A
  1. Na+ dependent Imino Transporter –> Imino glycinuria
  2. Cationic AAs and Cystine –> cystinuria
  3. Na+ dependent neutral AA transporter –> Hartnup disorder
  4. Na+ dependent Anionic AA transporter –> Dicarboxylic Aminoaciduria
35
Q

what are the 3 types of basolateral AA transporters?

A
  1. LAT1: cationic AA transporter (3° active transport)
  2. LAT 2: neutral AA transporter (2° active transport)
  3. other transporters (facilitated diffusion)
36
Q

how are AA reabsorbed in the kidney?

A

not all AA are absorbed by cells of the body during their first pass through the circulatory system but they’re retained in the blood because of the kidney that reabsorbs them so they aren’t lost in the urine!

AA would be excreted through the urine if the body already had all the AA it needed or if there was a kidney disease

37
Q

in what part of the glomular filtration system in the kidney are AA reabsorbed?

A

proximal tubule of the kidney

Amino acid transporters that are present at the polarized epithelial cells of the proximal tubules of kidney reabsorb >98% of the amount of amino acids that would otherwise be lost in urine.

38
Q

when will AA show up in the urine?

A

when there’s a defect in the transporters for reabsorption of that AA in the kidney

39
Q

when will AA show up in the feces?

A

if there’s a defect in their absorption at the small intestine

40
Q

AA absorption at the enterocytes of small intestine frequently involve what in a co-transport, secondary active transport type of transport mechanism?

A

Na+

2 active transport is used for absorption of AA from the intestinal lumen through the luminal cell membrane surface into the interior (cytoplasm) of enterocytes

for this to happen , AA transporters of this type most often are those that utilize co-transport of Na although some H+ cotransporters also function here

41
Q

what are glucogenic amino acids?

A

carbon skeletons of glucogenic AA can give rise to NET glucose production

their carbon skeletons are ultimately converted to either pyruvate or to 4 specific intermediates of the TCA cycle:

  1. α-ketoglutarate
  2. succinyl CoA
  3. fumarate
  4. oxaloacetate
42
Q

what are ketogenic amino acids?

A

the carbon skeletons of soley ketogenic AA are ultimately converted to either:

  1. acetyl CoA
  2. acetoacetyl CoA (which will covert to acetyl CoA usually)
43
Q

what’s the definition of “both glucogenic and ketogenic amino acids”?

A

AA that are both glucogenic and ketogenic are those for which part of their carbon skeleton is converted to a glucogenic molecule and the other part of their carbon skeleton is converted to a ketogenic molecule

44
Q

what are the stages of AA degradation?

A
  1. removal of the alpha-amino group by transamination
  2. the remaining carbon skeleton of the AA enters pathways of central metabolism as one of the 7 possible metabolic intermediates

depending on the particular AA being catabolized, its carbon skeleton is either soley glucogenic, soley ketogenic or both glucogenic and ketogenic

45
Q

what are the only 2 solely ketogenic AA?

A

leucine and lysine

46
Q

which of the 7 final metabolites that can give rise to net glucose formation? aka they’re glucogenic?

A
  1. pyruvate
  2. alpha-ketoglutarate
  3. succinyl CoA
  4. fumarate
  5. oxaloacetate

these can ultimately form oxaloacetate either via TCA cycle or by catabolism to pyruvate which is then converted to oxaloacetate

oxaloacetate can then be converted to phosphoenol pyruvate as the initial step in gluconeogenesis

47
Q

which of the 7 final metabolites are ketogenic?

A

acetyl CoA

acetoacetyl CoA (which will convert to Acetyl CoA

48
Q

what are the 7 metabolites whereby carbon skeletons of amino acids enter central pathways of metabolism?

A
  1. pyruvate
  2. alpha-ketoglutarate
  3. succinyl CoA
  4. fumarate
  5. oxaloacetate
  6. acetyl CoA
  7. acetoacetyl CoA
49
Q

why isn’t acetyl CoA glucogenic?

A

acetyl CoA comes into the TCA cycle so why aren’t those AA that give rise to acetyl CoA or to acetoacetyl CoA also glucogenic?

because a glucogenic AA has to give rise to NET glucose production and acetyl CoA only has 2 carbons that go into TCA cycle and they come right back out as CO2 so therefore the carbons of acetyl CoA can’t contribute any NET carbons to the synthesis of new glucose

50
Q

what are essential AA?

A

required synthetic pathways are not present in higher vertebrates such as humans

OR

they are not synthesized in adequate quantities in healthy adults and you have to ingest them via your diet

51
Q

what are non-essential AA?

A

readily made in the body from intermediates of central pathways so they are NOT REQUIRED in the diet

all AA are abundant in a diet containing sufficient protein

52
Q

what are conditionally essential AA?

A

can be synthesized by mammals but not in quantities that support growth of children or those under catabolic stress

53
Q

what are the essential AA?

A

PVT TIM LL

Phenylalanine
Valine
Threonine

Tryptophan
Isoleucine
Methionine

Histidine
Leucine
Lysine

54
Q

what are the conditionally essential AA?

A

arginine

histidine