amino acid oxidation I Flashcards
1
Q
T or F: we can store lots of amino acids
A
false; we can’t store them very well
2
Q
since we can’t store amino acids very well, what must we do?
A
we need to degrade them
3
Q
list 3 times in which we need to degrade amino acids
A
protein turnover, high-protein diet, starvation/diabetes
4
Q
describe why we need to degrade amino acids during protein turnover
A
degradation of old proteins can generate amino acids that are not needed for protein synthesis and are thus degraded themselves
5
Q
describe why we need to degrade amino acids when we have a high protein diet
A
more amino acids are ingested than the organism needs. We can’t store them, so we must degrade them
6
Q
describe why we need to degrade amino acids during starvation/diabetes
A
when carbs are unavailable, proteins are used as fuel, generating amino acids
7
Q
amino acid oxidation always begins with which step?
A
the loss of an amino group (backbone) to form the amino acid carbon skeleton (a-keto acid)
8
Q
in aa oxidation, what 2 things could happen to the a-keto acid/carbon skeleton once its formed
A
it can be fully oxidized to CO2 and H2O in the CAC, or it can be modified to provide intermediates for GNG
9
Q
T or F: NH4+ is very toxic
A
true
10
Q
in which organ is NH4+ especially toxic
A
the brain
11
Q
what can NH4+ toxicity cause in the brain (3)
A
cognitive impairment, seizures, and fatal swelling
12
Q
how do we combat NH4+ toxicity during aa breakdown?
A
production/transfer are carefully regulated + it’s often carried/excreted in less toxic forms
13
Q
T or F: blood ammonia levels are typically very low
A
true
14
Q
describe why ammonia is dangerous to the cellular level
A
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
15
Q
how does NH3 enter cells
A
simple diffusion bc it’s lipid soluble
16
Q
how does NH4+ enter cells
A
through aquaporins or K+ channels
17
Q
T or F: NH3 can cross the blood-brain barrier
A
true
18
Q
T or F: NH4+ can cross the blood-brain barrier
A
true
19
Q
list 5 things that NH4+ can do once in your cells
A
depolarize membrane potential (due to disrupted K+ levels), alter pH levels, cause swelling, inhibit the CAC, reduce glutamate and GABA levels (NTs)
20
Q
where does NH4+ start and end up during aa oxidation (hint: what body locations)
A
starts in extrahepatic tissues and ends up in the liver
21
Q
list 3 sources of NH4+
A
- 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
22
Q
NH4+ from protein turnover to the liver: what happens to free ammonia in extrahepatic tissues
A
it’s incorporated into glutamine (glutamate + NH4+ = glutamine)
23
Q
NH4+ from protein turnover to the liver: what happens once glutamine is generated in extrahepatic tissues
A
glutamine can move through the blood to the liver
24
Q
NH4+ from protein turnover to the liver: where does glutamine go once it arrives in the liver
A
mito matrix
25
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
26
NH4+ from protein turnover to the liver: what enzyme converts glutamine back to glutamate in the mito matrix
glutaminase
27
NH4+ from protein turnover to the liver: what is the by-product of converting glutamine back to glutamate
NH4+!
28
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
29
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
30
which enzymes do transaminations
aminotransferases
31
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
32
all aminotransferases have a prosthetic group called ________
pyridoxal phosphate (PLP)
33
pyridoxal phosphate (PLP) is derived from a __ vitamin
B
34
what is the name for the shallow depressions in the stomach
gastric pits
35
what do gastric pits open into
gastric glands
36
the gastric gland secretes enzymes required for ____
digestion
37
what do G cells secrete
gastrin
38
when do G cells secrete gastrin
when dietary protein enters the stomach
39
what do surface mucous cells secrete
mucus
40
what do mucous neck cells secrete
mucus
41
what do parietal cells secrete
HCl
42
what do chief cells secrete
pepsinogen
43
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
44
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
45
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+
46
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
47
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)
48
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
49
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
50
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)
51
what is alkaline tide
when HCO3- enters the blood after passage through the parietal cell antiporter. It raises blood pH after a meal
52
where in the parietal cell is H+/K+ ATPase located
apical membrane
53
where in the parietal cell is the chloride channel
apical membrane
54
where in the parietal cell is the Cl-/HCO3- antiporter
basolateral membrane
55
which enzyme generates bicarbonate
carbonic anhydrase
56
what is bicarbonate made from
CO2 and H2O
57
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
58
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
59
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
60
dietary NH4+ in intestines to the liver: low pH in the duodenum triggers it to _____________________
secrete the secretin hormone into the blood
61
dietary NH4+ in intestines to the liver: where is secretin hormone secreted (from the duodenum)
the blood
62
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
63
dietary NH4+ in intestines to the liver: what does the pancreas release to neutralize acidic content in the duodenum
bicarbonate
64
T or F: the pancreas is both an endocrine and exocrine gland
true
65
describe why the pancreas is an exocrine gland
exocrine function relates to digestion
66
describe why the pancreas is an endocrine gland
endocrine function relates to the maintenance of blood sugar levels
67
the exocrine cells of the pancreas are called ____
acini
68
what do acini produce
digestive enzymes
69
dietary NH4+ in intestines to the liver: where do the acini digestive enzymes go (from pancreas)
to the duodenum
70
how do acini digestive enzymes get to the duodenum from the pancreas
via a network of ducts
71
what produces pancreatic juice
acini
72
composition of pancreatic juice?
bicarbonate + other enzymes
73
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
74
dietary NH4+ in intestines to the liver: where is cholecystokinin released
into the blood
75
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
76
dietary NH4+ in intestines to the liver: list the 3 zymogens that are triggered to be released via cholecystokinin activity
trypsinogen, chymotrypsinogen, procarboxypeptidase
77
dietary NH4+ in intestines to the liver: list the active forms of the 3 zymogens that cholecystokinin triggers to be released
trypsin, chymotrypsin, carboxypeptidase
78
dietary NH4+ in intestines to the liver: role of the active zymogens?
cleavage of polypeptides at various points
79
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
80
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
81
NH4+ in skeletal muscle during exercise to the liver: what happens to the levels of aa ox during exercise/fasting
aa ox is upregulated
82
what happens to glycogen stores during exercise
they're depleted
83
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
84
during exercise, describe ATP needs for muscles
muscles need lots of ATP for constant contraction
85
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
86
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
87
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
88
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)
89
pyruvate + amino group = _______
alanine
90
NH4+ in skeletal muscle during exercise to the liver: which enzyme adds the amino group from glutamate to pyruvate to make alanine
alanine aminotransferase
91
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
92
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
93
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
94
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
95
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
96
once glutamate is in the liver from any of the three sources, what happens
amino group can be stripped away + excreted
97
where does oxidative deamination of glutamate occur
hepatocyte mito matrix
98
which enzyme is responsible for oxidative deamination of glutamate in liver mito matrix
glutamate dehydrogenase and NADP+
99
define transdeamination
the conversion of any aa to glutamate and then the removal of the glutamate NH4+ by glutamate dehydrogenase
100
list the 3 forms that excess amino groups leave the liver as
ammonia, urea, uric acid
101
in humans, the NH4+ is excreted as ___
urea
102
where does the urea cycle occur in the body
hepatocytes
103
where does the urea cycle occur in hepatocytes
mito matrix and cytosol
