amino acid oxidation I Flashcards
T or F: we can store lots of amino acids
false; we can’t store them very well
since we can’t store amino acids very well, what must we do?
we need to degrade them
list 3 times in which we need to degrade amino acids
protein turnover, high-protein diet, starvation/diabetes
describe why we need to degrade amino acids during protein turnover
degradation of old proteins can generate amino acids that are not needed for protein synthesis and are thus degraded themselves
describe why we need to degrade amino acids when we have a high protein diet
more amino acids are ingested than the organism needs. We can’t store them, so we must degrade them
describe why we need to degrade amino acids during starvation/diabetes
when carbs are unavailable, proteins are used as fuel, generating amino acids
amino acid oxidation always begins with which step?
the loss of an amino group (backbone) to form the amino acid carbon skeleton (a-keto acid)
in aa oxidation, what 2 things could happen to the a-keto acid/carbon skeleton once its formed
it can be fully oxidized to CO2 and H2O in the CAC, or it can be modified to provide intermediates for GNG
T or F: NH4+ is very toxic
true
in which organ is NH4+ especially toxic
the brain
what can NH4+ toxicity cause in the brain (3)
cognitive impairment, seizures, and fatal swelling
how do we combat NH4+ toxicity during aa breakdown?
production/transfer are carefully regulated + it’s often carried/excreted in less toxic forms
T or F: blood ammonia levels are typically very low
true
describe why ammonia is dangerous to the cellular level
NH3 acts as a gaseous weak base and NH4+ as an ionic weak acid. At cellular pH, we mainly have NH4+. NH4+ can enter cells through many types of K+ channels or aquaporins, and it can cross the blood brain barrier
how does NH3 enter cells
simple diffusion bc it’s lipid soluble
how does NH4+ enter cells
through aquaporins or K+ channels
T or F: NH3 can cross the blood-brain barrier
true
T or F: NH4+ can cross the blood-brain barrier
true
list 5 things that NH4+ can do once in your cells
depolarize membrane potential (due to disrupted K+ levels), alter pH levels, cause swelling, inhibit the CAC, reduce glutamate and GABA levels (NTs)
where does NH4+ start and end up during aa oxidation (hint: what body locations)
starts in extrahepatic tissues and ends up in the liver
list 3 sources of NH4+
- in protein/nucleotide turnover in extrahepatic cells
- in dietary amino acids, being absorbed by the intestine
- in amino acids in skeletal muscles, being degraded during exercise for fuel
NH4+ from protein turnover to the liver: what happens to free ammonia in extrahepatic tissues
it’s incorporated into glutamine (glutamate + NH4+ = glutamine)
NH4+ from protein turnover to the liver: what happens once glutamine is generated in extrahepatic tissues
glutamine can move through the blood to the liver
NH4+ from protein turnover to the liver: where does glutamine go once it arrives in the liver
mito matrix
NH4+ from protein turnover to the liver: what happens to glutamine once it enters the mito matrix of the liver
glutamine is converted back to glutamate via glutaminase
NH4+ from protein turnover to the liver: what enzyme converts glutamine back to glutamate in the mito matrix
glutaminase
NH4+ from protein turnover to the liver: what is the by-product of converting glutamine back to glutamate
NH4+!
NH4+ from protein turnover to the liver: after glutamate is regenerated and we get NH4+ in the liver, where does it go
it can now go off to make urea
NH4+ from protein turnover to the liver: what happens to the leftover glutamate in the liver (2)
most of it enters transamination reactions to generate other amino acids (enzyme = aminotransferases)
some can undergo further processing by glutamate dehydrogenase to release the backbone amine for excretion and produce more carbon skeletons for metabolites
which enzymes do transaminations
aminotransferases
NH4+ from protein turnover to the liver: when transaminations occur, what is the donor and what is the recipient of the amino group
excess glutamate donates the amino group to any a-keto acid
all aminotransferases have a prosthetic group called ________
pyridoxal phosphate (PLP)
pyridoxal phosphate (PLP) is derived from a __ vitamin
B
what is the name for the shallow depressions in the stomach
gastric pits
what do gastric pits open into
gastric glands
the gastric gland secretes enzymes required for ____
digestion
what do G cells secrete
gastrin
when do G cells secrete gastrin
when dietary protein enters the stomach
what do surface mucous cells secrete
mucus
what do mucous neck cells secrete
mucus
what do parietal cells secrete
HCl
what do chief cells secrete
pepsinogen
list 3 jobs of the gastrin hormone
stimulates muscular contractions to mix contents, stimulates pepsinogen secretion from chief cells, stimulates HCl secretion from parietal cells
dietary NH4+ in intestines to the liver: result of excess H+ secreted by parietal cells? (2)
causes low pH that helps kill any bacteria that enters the stomach with food. Also helps unfold globular proteins to expose internal peptide bonds
dietary NH4+ in intestines to the liver: how do parietal cells secrete H+ into the stomach lumen
they have a H+/K+ ATPase on the apical membrane facing the stomach lumen to release H+
dietary NH4+ in intestines to the liver: how do parietal cells secrete Cl- into the stomach
they have apical chloride channels to release Cl- into the stomach
dietary NH4+ in intestines to the liver: if parietal cells are secreting a bunch of H+ into the lumen, what happens to the pH of the CELL (not stomach)?
rises (we don’t want this)
dietary NH4+ in intestines to the liver: how do parietal cells combat raising pH as H+ is being pumped into the stomach
they have Cl-/HCO3- antiporter on the basolateral membrane that’s activated at high pH levels
dietary NH4+ in intestines to the liver: how does the parietal cell Cl-/HCO3- antiporter work
bicarbonate goes into the blood as chloride comes into the cell. Chloride can then exit on the apical side, and it will pump out bicarbonate in order to maintain pH of the parietal cell
dietary NH4+ in intestines to the liver: for HCl secretion in parietal cells, where does all the HCO3- and H+ come from
carbonic anhydrase catalyzes a reaction of water and CO2 to form H2CO3, and then bicarbonate. HCO3- entry into the blood after passage through the antiporter raises blood pH after a meal (alkaline tide)
what is alkaline tide
when HCO3- enters the blood after passage through the parietal cell antiporter. It raises blood pH after a meal
where in the parietal cell is H+/K+ ATPase located
apical membrane
where in the parietal cell is the chloride channel
apical membrane
where in the parietal cell is the Cl-/HCO3- antiporter
basolateral membrane
which enzyme generates bicarbonate
carbonic anhydrase
what is bicarbonate made from
CO2 and H2O
dietary NH4+ in intestines to the liver:: how is pepsin generated
low pH caused from parietal cells causes chief cells to release pepsinogen, which cleaves itself into active pepsin
dietary NH4+ in intestines to the liver: what does active pepsin do
hydrolyzes many peptide bonds = dietary proteins are degraded into smaller peptides in the stomach
dietary NH4+ in intestines to the liver: after being degraded in the stomach, acidic stomach contents then enter which part of the small intestine
duodenum
dietary NH4+ in intestines to the liver: low pH in the duodenum triggers it to _____________________
secrete the secretin hormone into the blood
dietary NH4+ in intestines to the liver: where is secretin hormone secreted (from the duodenum)
the blood
dietary NH4+ in intestines to the liver: what happens once secretin is secreted into the blood from the duodenum
it stimulates the pancreas to secrete bicarbonate into the duodenum to neutralize the HCl = pH rises
dietary NH4+ in intestines to the liver: what does the pancreas release to neutralize acidic content in the duodenum
bicarbonate
T or F: the pancreas is both an endocrine and exocrine gland
true
describe why the pancreas is an exocrine gland
exocrine function relates to digestion
describe why the pancreas is an endocrine gland
endocrine function relates to the maintenance of blood sugar levels
the exocrine cells of the pancreas are called ____
acini
what do acini produce
digestive enzymes
dietary NH4+ in intestines to the liver: where do the acini digestive enzymes go (from pancreas)
to the duodenum
how do acini digestive enzymes get to the duodenum from the pancreas
via a network of ducts
what produces pancreatic juice
acini
composition of pancreatic juice?
bicarbonate + other enzymes
dietary NH4+ in intestines to the liver: if the incoming stomach contents to the duodenum contained amino acids, what is the duodenum triggered to release
cholecystokinin
dietary NH4+ in intestines to the liver: where is cholecystokinin released
into the blood
dietary NH4+ in intestines to the liver: what does cholecystokinin in the blood do
stimulates the pancreas exocrine cells to release zymogens in the pancreatic juice
dietary NH4+ in intestines to the liver: list the 3 zymogens that are triggered to be released via cholecystokinin activity
trypsinogen, chymotrypsinogen, procarboxypeptidase
dietary NH4+ in intestines to the liver: list the active forms of the 3 zymogens that cholecystokinin triggers to be released
trypsin, chymotrypsin, carboxypeptidase
dietary NH4+ in intestines to the liver: role of the active zymogens?
cleavage of polypeptides at various points
dietary NH4+ in intestines to the liver: once polypeptides are fully degraded in the intestine, what happens to dipeptides/free amino acids?
they’re absorbed by intestinal mucosa cells of villi + then enter capillaries
dietary NH4+ in intestines to the liver: describe the path of free amino acids/peptides in the small intestine to the liver
intestinal lumen, epithelial cells via villi, blood via capillaries, hepatic portal vein, liver
NH4+ in skeletal muscle during exercise to the liver: what happens to the levels of aa ox during exercise/fasting
aa ox is upregulated
what happens to glycogen stores during exercise
they’re depleted
during exercise, are there aerobic or anaerobic conditons? explain
potentially anaerobic: blood can’t pump O2 to tissues fast enough. Lactic acid fermentation occurs instead of CAC after glycolysis
during exercise, describe ATP needs for muscles
muscles need lots of ATP for constant contraction
NH4+ in skeletal muscle during exercise to the liver: describe what happens after proteins are broken down to amino acids
transaminations can convert all those amino acids to glutamate
NH4+ in skeletal muscle during exercise to the liver: in order to convert all amino acids to glutamate, which molecule must serve as the amino group acceptor? in which process does this molecule typically participate in?
a-KG is the amino group acceptor to form glutamate. a-KG is a CAC intermediate
NH4+ in skeletal muscle during exercise to the liver: once we have glutamate, it would be converted to glutamine. However, in exercising skeletal muscle we cannot do this. Why not?
glutamate to glutamine costs ATP, and skeletal muscle doesn’t have any to spare
NH4+ in skeletal muscle during exercise to the liver: since we can’t convert glutamate to glutamine, what must we do
glutamate gives its amino group to pyruvate (transamination)
pyruvate + amino group = _______
alanine
NH4+ in skeletal muscle during exercise to the liver: which enzyme adds the amino group from glutamate to pyruvate to make alanine
alanine aminotransferase
NH4+ in skeletal muscle during exercise to the liver: what does alanine do once it’s made in the muscle
travels through the blood to the liver
NH4+ in skeletal muscle during exercise to the liver: what happens to alanine once it arrives in the liver
undergoes an aminotransferase reaction in reverse to regenerate glutamate and pyruvate. Glutamate will add to the existing pool of glutamate in the liver
NH4+ in skeletal muscle during exercise to the liver: what happens to the build up of pyruvate in the liver (after alanine is broken down)
pyruvate undergoes GNG in the liver to regenerate glucose
NH4+ in skeletal muscle during exercise to the liver: what happens to the glucose in the liver (generated from pyruvate GNG)
glucose travels back to muscle in the blood
benefit of glucose-alanine cycle? (4)
it gets toxic NH4+ to the liver from aa ox but keeps all the ATP in skeletal muscle available for muscle contraction. There’s still an ATP cost, but the liver is less needy during exercise. Blood glucose levels are also raised. Glucose gets to muscle which needs it during exercise
once glutamate is in the liver from any of the three sources, what happens
amino group can be stripped away + excreted
where does oxidative deamination of glutamate occur
hepatocyte mito matrix
which enzyme is responsible for oxidative deamination of glutamate in liver mito matrix
glutamate dehydrogenase and NADP+
define transdeamination
the conversion of any aa to glutamate and then the removal of the glutamate NH4+ by glutamate dehydrogenase
list the 3 forms that excess amino groups leave the liver as
ammonia, urea, uric acid
in humans, the NH4+ is excreted as ___
urea
where does the urea cycle occur in the body
hepatocytes
where does the urea cycle occur in hepatocytes
mito matrix and cytosol
