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

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2
Q

since we can’t store amino acids very well, what must we do?

A

we need to degrade them

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3
Q

list 3 times in which we need to degrade amino acids

A

protein turnover, high-protein diet, starvation/diabetes

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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

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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

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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

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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)

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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

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9
Q

T or F: NH4+ is very toxic

A

true

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10
Q

in which organ is NH4+ especially toxic

A

the brain

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11
Q

what can NH4+ toxicity cause in the brain (3)

A

cognitive impairment, seizures, and fatal swelling

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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

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13
Q

T or F: blood ammonia levels are typically very low

A

true

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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

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15
Q

how does NH3 enter cells

A

simple diffusion bc it’s lipid soluble

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16
Q

how does NH4+ enter cells

A

through aquaporins or K+ channels

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17
Q

T or F: NH3 can cross the blood-brain barrier

A

true

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18
Q

T or F: NH4+ can cross the blood-brain barrier

A

true

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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)

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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

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21
Q

list 3 sources of NH4+

A
  1. in protein/nucleotide turnover in extrahepatic cells
  2. in dietary amino acids, being absorbed by the intestine
  3. in amino acids in skeletal muscles, being degraded during exercise for fuel
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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)

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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

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24
Q

NH4+ from protein turnover to the liver: where does glutamine go once it arrives in the liver

A

mito matrix

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25
Q

NH4+ from protein turnover to the liver: what happens to glutamine once it enters the mito matrix of the liver

A

glutamine is converted back to glutamate via glutaminase

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26
Q

NH4+ from protein turnover to the liver: what enzyme converts glutamine back to glutamate in the mito matrix

A

glutaminase

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27
Q

NH4+ from protein turnover to the liver: what is the by-product of converting glutamine back to glutamate

A

NH4+!

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28
Q

NH4+ from protein turnover to the liver: after glutamate is regenerated and we get NH4+ in the liver, where does it go

A

it can now go off to make urea

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29
Q

NH4+ from protein turnover to the liver: what happens to the leftover glutamate in the liver (2)

A

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

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30
Q

which enzymes do transaminations

A

aminotransferases

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31
Q

NH4+ from protein turnover to the liver: when transaminations occur, what is the donor and what is the recipient of the amino group

A

excess glutamate donates the amino group to any a-keto acid

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32
Q

all aminotransferases have a prosthetic group called ________

A

pyridoxal phosphate (PLP)

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33
Q

pyridoxal phosphate (PLP) is derived from a __ vitamin

A

B

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34
Q

what is the name for the shallow depressions in the stomach

A

gastric pits

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35
Q

what do gastric pits open into

A

gastric glands

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36
Q

the gastric gland secretes enzymes required for ____

A

digestion

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37
Q

what do G cells secrete

A

gastrin

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38
Q

when do G cells secrete gastrin

A

when dietary protein enters the stomach

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39
Q

what do surface mucous cells secrete

A

mucus

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40
Q

what do mucous neck cells secrete

A

mucus

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41
Q

what do parietal cells secrete

A

HCl

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42
Q

what do chief cells secrete

A

pepsinogen

43
Q

list 3 jobs of the gastrin hormone

A

stimulates muscular contractions to mix contents, stimulates pepsinogen secretion from chief cells, stimulates HCl secretion from parietal cells

44
Q

dietary NH4+ in intestines to the liver: result of excess H+ secreted by parietal cells? (2)

A

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
Q

dietary NH4+ in intestines to the liver: how do parietal cells secrete H+ into the stomach lumen

A

they have a H+/K+ ATPase on the apical membrane facing the stomach lumen to release H+

46
Q

dietary NH4+ in intestines to the liver: how do parietal cells secrete Cl- into the stomach

A

they have apical chloride channels to release Cl- into the stomach

47
Q

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)?

A

rises (we don’t want this)

48
Q

dietary NH4+ in intestines to the liver: how do parietal cells combat raising pH as H+ is being pumped into the stomach

A

they have Cl-/HCO3- antiporter on the basolateral membrane that’s activated at high pH levels

49
Q

dietary NH4+ in intestines to the liver: how does the parietal cell Cl-/HCO3- antiporter work

A

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
Q

dietary NH4+ in intestines to the liver: for HCl secretion in parietal cells, where does all the HCO3- and H+ come from

A

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
Q

what is alkaline tide

A

when HCO3- enters the blood after passage through the parietal cell antiporter. It raises blood pH after a meal

52
Q

where in the parietal cell is H+/K+ ATPase located

A

apical membrane

53
Q

where in the parietal cell is the chloride channel

A

apical membrane

54
Q

where in the parietal cell is the Cl-/HCO3- antiporter

A

basolateral membrane

55
Q

which enzyme generates bicarbonate

A

carbonic anhydrase

56
Q

what is bicarbonate made from

A

CO2 and H2O

57
Q

dietary NH4+ in intestines to the liver:: how is pepsin generated

A

low pH caused from parietal cells causes chief cells to release pepsinogen, which cleaves itself into active pepsin

58
Q

dietary NH4+ in intestines to the liver: what does active pepsin do

A

hydrolyzes many peptide bonds = dietary proteins are degraded into smaller peptides in the stomach

59
Q

dietary NH4+ in intestines to the liver: after being degraded in the stomach, acidic stomach contents then enter which part of the small intestine

A

duodenum

60
Q

dietary NH4+ in intestines to the liver: low pH in the duodenum triggers it to _____________________

A

secrete the secretin hormone into the blood

61
Q

dietary NH4+ in intestines to the liver: where is secretin hormone secreted (from the duodenum)

A

the blood

62
Q

dietary NH4+ in intestines to the liver: what happens once secretin is secreted into the blood from the duodenum

A

it stimulates the pancreas to secrete bicarbonate into the duodenum to neutralize the HCl = pH rises

63
Q

dietary NH4+ in intestines to the liver: what does the pancreas release to neutralize acidic content in the duodenum

A

bicarbonate

64
Q

T or F: the pancreas is both an endocrine and exocrine gland

A

true

65
Q

describe why the pancreas is an exocrine gland

A

exocrine function relates to digestion

66
Q

describe why the pancreas is an endocrine gland

A

endocrine function relates to the maintenance of blood sugar levels

67
Q

the exocrine cells of the pancreas are called ____

A

acini

68
Q

what do acini produce

A

digestive enzymes

69
Q

dietary NH4+ in intestines to the liver: where do the acini digestive enzymes go (from pancreas)

A

to the duodenum

70
Q

how do acini digestive enzymes get to the duodenum from the pancreas

A

via a network of ducts

71
Q

what produces pancreatic juice

A

acini

72
Q

composition of pancreatic juice?

A

bicarbonate + other enzymes

73
Q

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

A

cholecystokinin

74
Q

dietary NH4+ in intestines to the liver: where is cholecystokinin released

A

into the blood

75
Q

dietary NH4+ in intestines to the liver: what does cholecystokinin in the blood do

A

stimulates the pancreas exocrine cells to release zymogens in the pancreatic juice

76
Q

dietary NH4+ in intestines to the liver: list the 3 zymogens that are triggered to be released via cholecystokinin activity

A

trypsinogen, chymotrypsinogen, procarboxypeptidase

77
Q

dietary NH4+ in intestines to the liver: list the active forms of the 3 zymogens that cholecystokinin triggers to be released

A

trypsin, chymotrypsin, carboxypeptidase

78
Q

dietary NH4+ in intestines to the liver: role of the active zymogens?

A

cleavage of polypeptides at various points

79
Q

dietary NH4+ in intestines to the liver: once polypeptides are fully degraded in the intestine, what happens to dipeptides/free amino acids?

A

they’re absorbed by intestinal mucosa cells of villi + then enter capillaries

80
Q

dietary NH4+ in intestines to the liver: describe the path of free amino acids/peptides in the small intestine to the liver

A

intestinal lumen, epithelial cells via villi, blood via capillaries, hepatic portal vein, liver

81
Q

NH4+ in skeletal muscle during exercise to the liver: what happens to the levels of aa ox during exercise/fasting

A

aa ox is upregulated

82
Q

what happens to glycogen stores during exercise

A

they’re depleted

83
Q

during exercise, are there aerobic or anaerobic conditons? explain

A

potentially anaerobic: blood can’t pump O2 to tissues fast enough. Lactic acid fermentation occurs instead of CAC after glycolysis

84
Q

during exercise, describe ATP needs for muscles

A

muscles need lots of ATP for constant contraction

85
Q

NH4+ in skeletal muscle during exercise to the liver: describe what happens after proteins are broken down to amino acids

A

transaminations can convert all those amino acids to glutamate

86
Q

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

a-KG is the amino group acceptor to form glutamate. a-KG is a CAC intermediate

87
Q

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?

A

glutamate to glutamine costs ATP, and skeletal muscle doesn’t have any to spare

88
Q

NH4+ in skeletal muscle during exercise to the liver: since we can’t convert glutamate to glutamine, what must we do

A

glutamate gives its amino group to pyruvate (transamination)

89
Q

pyruvate + amino group = _______

A

alanine

90
Q

NH4+ in skeletal muscle during exercise to the liver: which enzyme adds the amino group from glutamate to pyruvate to make alanine

A

alanine aminotransferase

91
Q

NH4+ in skeletal muscle during exercise to the liver: what does alanine do once it’s made in the muscle

A

travels through the blood to the liver

92
Q

NH4+ in skeletal muscle during exercise to the liver: what happens to alanine once it arrives in the liver

A

undergoes an aminotransferase reaction in reverse to regenerate glutamate and pyruvate. Glutamate will add to the existing pool of glutamate in the liver

93
Q

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)

A

pyruvate undergoes GNG in the liver to regenerate glucose

94
Q

NH4+ in skeletal muscle during exercise to the liver: what happens to the glucose in the liver (generated from pyruvate GNG)

A

glucose travels back to muscle in the blood

95
Q

benefit of glucose-alanine cycle? (4)

A

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
Q

once glutamate is in the liver from any of the three sources, what happens

A

amino group can be stripped away + excreted

97
Q

where does oxidative deamination of glutamate occur

A

hepatocyte mito matrix

98
Q

which enzyme is responsible for oxidative deamination of glutamate in liver mito matrix

A

glutamate dehydrogenase and NADP+

99
Q

define transdeamination

A

the conversion of any aa to glutamate and then the removal of the glutamate NH4+ by glutamate dehydrogenase

100
Q

list the 3 forms that excess amino groups leave the liver as

A

ammonia, urea, uric acid

101
Q

in humans, the NH4+ is excreted as ___

A

urea

102
Q

where does the urea cycle occur in the body

A

hepatocytes

103
Q

where does the urea cycle occur in hepatocytes

A

mito matrix and cytosol