Week 14 - Unit 4 Flashcards

1
Q

Proteases are secreted from the exocrine pancreas as ________.

A

Zymogens - require activation for enzyme function

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2
Q

Before a protein is recycled it has to be ________ by a family of transaminases , which allows the carbon backbone to be used for GNG or energy.

A

Deaminated

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3
Q

Ammonia released from the process of Deamination of AA is used by the ____ cycle. The cycle occurs in the liver and takes the Ammonia that must transported as _____or ______ and used to synthesize urea as a means of disposing of the ______. Critical cycle as ammonia is toxic to the body.

A

Urea

Alanine
Glutamine

Nitrogen

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4
Q

In the stomach what two things start to digest proteins?

What will protein be reduced to ?

A
  1. HCL(Acid)
  2. Pepsin (enzyme)\

Polypeptide chains

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5
Q

After the stomach, the Pancreas will secrete what 5 things to cleave the Polypeptides into Di and Tri peptides in the small intestine?

A
  1. (HCO3-) -bicarbonate
  2. TrypsinOGEN
  3. ChomotrypsinOGEN
  4. PROelastase
  5. PROcarboxypeptidases A and B

(Remove capital letters to make active)

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6
Q

All of the enzymes secreted from the pancreas are secreted as ?

A

Zymogens that must be activated (cleaved to activate)

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7
Q

Di and Tri peptides and free AA are taken up by ______ ______ cells through similar mechanisms as Glucose. It uses ______ _____ transport and SOME_____ transport mechanisms.

A

Intestinal epithelial (small intestine)

Secondary active

Facilitated

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8
Q

What 2 things can Pepsinogen be activated by and activated to what?

A

Acid (HCL) or autocatalyzed cleavage

Generates Pepsin

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9
Q

For the enzymes secreted by the pancreas, what will be the first activate enzyme in the cleavage cascade and what is the enzyme that starts the cleavage?

A

Trypsinogen ———> Trypsin

Enteropeptidase (Enterokinase) will cleave

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10
Q

Active Trypsin will cleave and be the activator for what other 3 Zymogens (proenzymes) secreted by the pancrease for digestion of Bi and Tri -peptides ?

A
  1. Chymotrypsinogen———> Chomotrypsin
  2. Proelastase ——————> Elastase
  3. Procarboxypeptidases—->Carboxypeptidases
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11
Q

The __________ transporter will generate the ____ gradient by pumping it out to keep concentrations low in the intestinal lumen for secondary active transport of the AA paired to it into the cell.

A

Sodium-ATPase

Sodium

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12
Q

On the ______ ____ of Intestinal cells, the AA will move into the blood stream through _______ transport.

A

Serosal side

Facilitated

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13
Q

The (gamma) y-Glutamyl cycle is necessary for the synthesis of _______.

A

Glutathione - required to maintain reduced state of Iron in RBC

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14
Q

In Step one of y-Glutamyl Cycle, the y-glutamyl transpeptidase (in membranse) will conjugate an AA to generate _________ on the inside of the cell.

A

y-Glutamylamino acid

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15
Q

In step two, of y-Glutamyl cycle, the y-Glutamylamino acid will release the _____ and continue cycle to create_____.

A

AA

Glutathione

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16
Q

Many cells have the inner cell pathway to produce Glutathione, but few cells have the ________ ______. So it does not play a large role in AA uptake.

A

y-Glutamyl transpeptidase

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17
Q

There are two major pathways for protein recycling in the cell, what are they?

A
  1. Lysosomal degradation due to Autophagy

2. Protein ubiquinination and protosomal degradation

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18
Q

In autophagy/lysosomal degradation in the cell, it involves ______ and the molecular intermediate ______.

A

AMP-kinase (AMPK)

mTOR

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19
Q

Under low energy when AMP is high and ATP is low, the signal of this condition will activate _______. This will lead to the phosphorylation (activation) of the complex ________ _____ ______ .

A

AMP-kinase

Tuberous sclerosis complex 1 and 2 (TSC1/2)

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20
Q

When TSC1/2 is phosphorylated and activated by AMP-kinase, then it will activate the GTPase activity of the small protein ______. The GTPase activity will convert it to the _______ which inactivates itself.

A

Rheb (Rheb-GTPase)

Rheb-GDP

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21
Q

Inactivation of Rheb (now as Rheb GDP), will inactivate ______ which then releases the inhibition that _____ was putting on _______.

A

mTOR
mTOR

Autophagy (now lysosomes can degragate and recycle proteins)

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22
Q

When Rheb is inactive, what is also then inactivated?

A

mTOR (Rheb no longer available to activate mTOR)

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23
Q

(Autophagy pathway) When energy is high in the cell , in the form of insulin, that will phosphorylate _______ at an alternative site(this will be inhibition), then leading to ____ _____ activity.

A

TSC1/2

Rheb - GTP

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24
Q

During the autophagy pathway, when there is Rheb-GTP activity, this will activate ______ which will inhibit process of _______ and inhibit recycling so thereby increasing protein ______. This process controls protein synthesis vs. degradation and which will occur.

A

mTOR

Autophagy

synthesis

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25
When insulin is present (high energy) , fill in the blanks for the Autophagy pathway? Insulin----> ____ TSC1----->____Rheb--->____mTOR
Inhibits (TSC1) Activates (Rheb) Activates (mTOR)
26
Ubiquitin is a small protein of appx. ____ AA. It can be added to the amino group in _______ resides of proteins that cells want to degrade. Targets the protein.
76 Lysine
27
The proteasome complex used in Ubiquitination protein degradation will involve a ______ proteasome subunit and a _____ regulatory particle.
20S 19S
28
The _____ regulatory peptide particle will bind on top of the _____ proteasome (cylinder shape) complex. They will form a ____ complex that requires _____ energy for combination.
19S 20S 26S ATP
29
The movement of the polypeptide into the proteasome for degradation will require ____. Once the Polypeptide is digested, the ____ are released into the cytosol and can be used for ______ or _____ in the cell.
ATP AA Protein synthesis Energy
30
What AA will help rapidy turn over and target Polypeptides into proteasome complexes?
1. Proline 2. Glutamate 3. Serine 4. Threonine
31
The AA Proline, Glutamate, Serine, and Threonine will form a _______ domain, and that will target proteins carrying such domains for ubiquitination and rapid turn over in cell.
PEST
32
True or False: | The 20S proteasome can have only one 19S regulatory particle associated with it.
False - it can have two- one on top and one on bottom
33
Besides the digestive proteases, what are the main 6 proteases involved in protein turnover/degradation?
1. Cathepsins 2. Caspases 3. Matrix Metalloproteinases 4. Proteasome (ubiquitin-tagged proteins) 5. Serine Proteases 6. Calpains
34
_____ will use the mechanism of cysteine proteases and play a role in Lysosomal enzymes for protein turnover/degradation.
Cathepsins
35
______ will use the mechanism of Cysteine proteases and cleave after aspartate and play a role in Apoptosis
Caspases
36
______ _______ require zinc for catalysis and are used as proteases for ____ ____.
Matrix Metalloproteinases Matrix degradation
37
Diseases can be caused by deficencies in the facilitated membrane transport proteins such as ______ and ______.
Cystinuria (cystine uptake affected- kidney stones) Hartnup Disease (Trasporter B- for neutral AA is impaired, pellagra-like symptoms due to lack to tryptophan)
38
______ disease is not due to problems in transporters or (genetic reasons) turnover, but rather due to environmental causes- protein calorie malnutrition- leading to excessive protein degradation in extremites and edema.
Kwashiorkior
39
Cystic Fibrosis (genetic) impacts digestion due to a deficiency in a ____ transporter in the pancreas. This impacts the water balance in the pancreas which causes what?
Chloride Problems in secretion of diegestive enzymes from pancreas - so problems in normal nutrient degradation and absorption (protein)
40
In Cystic Fibrosis the secretion of enzymes from the pancreas will be ______ and not as _____ due to the problems in water balance. This makes the enzymes less effective in digestion.
mucous-y fluid
41
What are the four main diseases or disorders covered that can cause protein turnover/degradation issues?
1. Cystic fibrosis (genetic) 2. Cystinuria (genetic) 3. Kwashiorkor (Enviornmental) 4. Hartnup Disease (Genetic)
42
In the body, excess AA will have its _____ taken and used for Storage or energy, and it will have the _____ taken for the ____ cycle or to create ______.
Carbon Nitrogen Urea, Aspartate
43
The Urea cycle is for detoxifying Ammonium ions (NH4) and incoporating them into Urea as ______.
NH2
44
Ammonium ions (NH4) are the most prevelent in the body as the pKa is _____. Such that the ______form is the most common molecule. However ____ ______ can also be found and is essential for disposal of protons in kidney.
9.3 Protonated Free Ammonia
45
In the Urea cycle it can be activated in both the ____ and _____ state. It is a function of the excess of ____ in the body.
Fed Fasted AA
46
In the fed state for the Urea cycle, the free ammonium ion can be used in the _____ cycle, the carbon can be used to make _____ or _______ or ____.
Urea Glucose Triacylglycerols Protein synthesis
47
In the Fasting state for Urea cycle, GNG is occuring and the primary substrate for GNG from the skeletal muscle is ______. The AA are then taken to the liver and ______ and the Ammonium ion is used to generate Urea.
Alanine (other AA too) Deaminated
48
The movement of Ammonia(NH3) in the urea cycle requires _______ reactions that require the co-factor _____.
Transamination PLP (pyroxidylphosphate)
49
In the Transamination reaction, the substrates Aspartate and Alpha-KeoGlutarate will react , with _______ present, and then the (NH3) Ammonia will transfer to the Alpha-keto Glutarate to make _______ and the Aspartate will turn into its conjugate_________. These reactions are reversible.
PLP (pyroxidylphosphate) Glutamate (new AA) Oxaloacetate (keto acid of Aspartate)
50
There are several pathways that shuttle into the generation of Ammonium (NH4). ______ and ______ have several amides in their structure and when catalyzed they will release free ammonia.
Glutamine Asparagine
51
Glutamine is deaminated to _______ which then can then be further deaminated to _______ by the enzyme _________.
Glutamate Alpha-keto Glutarate Glutamate Dehydrogenase (GDH)
52
Glutamate Dehydrogenase will free an _______ from ______ to make _________. This action is reversible.
Ammonium (NH4) Glutamate Alpha-Keto Glutarate
53
The release of Ammonium from Glutamate with GDH will require either _____ or _______ to pick up the extra _______.
NAD+ NADP+ Hydrogen
54
Ammonium can either be freed from an ___ or fixed to a _______.
AA Keto-acid
55
Serine will contribute ammonium to the pool when deaminated to form ________ with ______ as a cofactor enzyme.
Pyruvate PLP
56
Threonine can contribute ammonium to the pool when deaminated to form _______ with ____ as a cofactor to the enzyme.
Alpha-ketobutyrate PLP
57
Histidine can be deaminated to contribute Ammonium to the (NH4) pool in the blood and it turns into ______.
Urocanate
58
What are the 6 AA that can be deaminated to contribute Ammonium to the pool ?
1. Asparagine 2. Glutamine 3. Glutamate 4. Serine 5. Threonine 6. Hisitidine
59
Besides the free AA that can be deaminated in the body, the _____ _____ cycle in the brain and the muscle can release ammonium and be scavanged by _______ which will then transfer the Nitrogen to OAA to form ________.
Purine Nucleotide Glutamate Aspartate
60
What is released after the Aspartate gets its Nitrogen from Glutamate after the Aspartate enters the Purine nucleotide cycle (brain and muscle) ?
Fumarate released after the Nitrogen is contributed to form Purine ring structure
61
The reaction of Glutamate with the enzyme GDH to form Alpha-Keto Glutarate will occur in the ______. The reaction direction is important as ______ will be released to form Urea.
MT Ammonium (NH4)
62
Glutamate can be generated using Transamination using ______ or through the enzyme ______ both from the substance of _______.
PLP GDH Alpha-keto Glutarate
63
Glutamate will act as an Ammonia acid carrier for _____ synthesis and will react with any number of ______ plus _____ to form AA and turn itself back into Alpha-ketoglutarate.
AA Alpha-keto acids PLP
64
Shuttling of Ammonium in the body starts with any AA being transaminated with _______ to form the main carrier of Nitrogen ________.
Alpha-ketoglutarate Glutamate
65
After the Glutamate is formed, it can be transaminated (PLP) itself to turn OAA into ________ (can enter Urea cycle) or acted on by GDH directly to donate NH4+ to the ______ cycle.
Aspartate Urea
66
In the Glucose-Alanine Cycle ,the use of _______ is a primary shuttle for moving Ammonium to the liver from Muscles. In this cycle broken down AA will give amide group to A-KetoG, which then turns into Glutamate, and Glutamate will give amide group to _______ which then makes Alanine to be shuttled to liver.
Alanine Pyruvate
67
In the Glucose-Alanine cycle, once the Alanine is shuttled to the liver it can be divided in to the Nitrogen part that is converted into ______ and into its Carbon parts that will be converted to ______ and shuttled back to muscle for energy.
Urea Glucose
68
In addition to Alanine, ______ is also used as a non-toxic shuttle for Ammonium . In this cycle, Free Ammonium will be fixed to A-KG by______ to make Glutamate.
Glutamine GDH (plus NADH or NADPH to add H)
69
In the Glutamine shuttle, once Glutamate is made in the muscle/peripheral tissue, another free Ammonium is added to it by _______ plus energy from ______ to make ________ to be transported back to the liver.
Glutamine synthetase ATP Glutamine
70
In the liver the Glutamine will contribute ____ Ammonium groups that are used in Urea cycle. The first Ammonium is released by ______ (then making glutamate) and the second is released by _______. With both ammoniums becoming free to enter Urea cycle.
2 Glutaminase GDH
71
Nitrogen transport in most peripheral tissues occurs using the ______ _____ enzyme that will fix free Ammonium to ______ to make _______.
Glutamine synthetase Glutamate Glutamine
72
Nitrogen transport in the Muscle will primarily use the _____ ____ cycle. In this cycle, Free Ammonium is fixed to Alpha-keto Glutarate to make Glutamate by _______ and then it is transaminated to ______ to make ________ which is then shuttled in the blood to the liver.
Alanine- Glucose GDH (enzyme) Pyruvate Alanine (enters the liver and transaminated back to pyruvate in liver)
73
True or False: The urea cycle will be most active in a pregnant female and a 10 year old male child as compared to a 25 year old male Postprandially
False- there is a lot of protein synthesis occurring so the AA pool is low for available degradation .
74
Which individual will the urea cycle be more active in: 1. In a 25 year old male fasted for 48 hours 2. Postprandially in a 48 year old male who consumes a typical American diet
2. 48 year old male- less protein turnover so more AA avaliable for degradation as compared to the 25 year old (Urea cycle will then be more active in 48 year old)
75
The Urea cycle consists of ____ interactions that occur primarily in the liver and in the cells _____ and _____.
5 Cytosol MT
76
The Urea cycle starts in the MT with the enzyme ____________. This initial reaction involves the condensation of ____ with First ______ ion (free). This generates ______ ________.
Carbamoyl Phosphate synthetase 1 (CPS 1) CO2 with Ammonium Carbamoyl Phosphate (2-ATP needed)
77
In the second step of Urea Cycle after CPS1 is used, _____ ______ will react with _______ using the enzyme _____ _______. This will form the Citruline the will exit the MT.
Carbamoyl Phosphate Ornithine Ornithine Trascarbamoylase
78
OAA can be transaminated to form _______ which is then added (using ATP) to the _____that exits the MT into the Cytosol.
Aspartate Cirtruline
79
What is the enzyme that will combine Cirtruline and Aspartate in the cytosol to form Arginnosuccinate ?
Arginnosuccinate synthetase
80
What is the name of the product after combining Cirtruline and Aspartate?
Arginnosuccinate
81
In the Urea cycle, what happens after the formation of Arginnosuccinate ?
It can be cleaved into Fumarate and Arginine
82
What enzyme will split the Argininosuccinate into Arginine and Fumarate? Which one is carring the 2 Nitrogens?
Argininosuccinate lyase Arginine
83
What enzyme will use H2O and hydrolyze the Urea off of Arginine to then reform ________?
Arginase (enzyme) Ornithine
84
What is the Urea molecule composed of ?
- One Carbon - NH2 on either side of Carbon - Double bond Oxygen on top of Carbon
85
Fumarate can then be converted to ______ using the cytoplasmic Fumarase enzyme . This will then be used for the synthesis of _____ in ____.
Malate Glucose GNG
86
Ornithine is an AA but is not incorporated into proteins during _____ ______. There is no genetic codon for this AA>
Protein Synthesis
87
The primary regulation of the Urea cycle is at the enzyme ________. It requires _______ as an allosteric activator.
CPS1 (Carbamoyl Phosphate synthetase 1) N-Acetyl Glutamate
88
________ is an allosteric activator necessary for the reaction with enzyme CPS1 involving the initial CO2 to interact with the Ammonium Ion to Condense into _______.
N-Acetyl Glutamate Carbamoyl phosphate
89
The synthesis of N-Acetyl Gutamate is depended on levels of _______ and _______. This synthesis is stimulated by levels of ______.
Glutamate Acetyl CoA Arginine
90
As ______ is produced in the Urea cycle, an increase in the cycles activity will stimulate activity of _______ which then will stimulate the activity of ________. This is the primary regulation of Urea Cycle.
Arginine N-Acetyl-Glutamate CPS1
91
During fasting the liver's primary role is to synthesis Glucose usually through _____. This process will utilize AA primarily in the form of _____ as a substrate .
GNG L-alanine
92
The release of Glucagon and Cortisol stimulates the release of ______ from Skeletal Muscle. It can be taken up in the liver and transaminated to ________. This is used for GNG.
L-ALanine Pyruvate
93
When L-alanine is transaminated to Pyruvate, what is the other substance converted?
Alpha keto-glutarate is being aminated to make Glutamate
94
In the liver, once A-KetoG was aminated into Glutamate (carrying the NH4) then it can either be acted on by NAD+ and _____ to release the NH4, or it can be deaminated back to its keto version and turn OAA into ______.
GDH Aspartate (will donate second NH4 in urea cycle)
95
The Urea cycle is an energy _____ process.
Requiring
96
In a patient whom orotic acid levels are elevated you would suspect what?
Ornithine transcarbamoylase is inactive (defiecent) | orotic acid can not react with Carbomyl phosphate to create Citruline so the Ornithine will build up
97
In the Urea cycle, the _______ and its product _____ share a transporter in the MT membrane and ____ will exit the MT to react with Aspartate.
Ornithine Cirtruline Cirtruline
98
In the Urea cycle, the _______ and its product _____ share a transporter in the MT membrane and ____ will exit the MT to react with Aspartate.
Ornithine Citruline Citruline
99
Most deficiencies in Urea Cycle are autosomal recessive (need rr) but the exception to the rule is _______ _________ deficiency and is an X-linked deficiency. In such X-linked traits, you will find variable _______with either problems in regular circumstances in the Urea cycle or only under extreme conditions (Exposure to chemicals like pesticides high in Nitrogen that needs to be detoxified in the body).
Ornithine transcarbamoylase Phenotypes
100
In the case of some Urea cycle disorders, ______ will become an essential amino acid. Meaning if it is not synthesized in the Urea cycle, it must be supplied by an ______ source.
Arginine Exogenous
101
The individual with an Ornithine Transcarbamoylase deficiency (Orotic acid build up) was infused with: Sodium Benzoate Sodium Phenylacetate Arginine Free base Intravenous glucose and Hemodialysis was started, and then Ammonia level gradually dropped. What is the rationale for administration of Benzoate and phenylacetate?
Both Sodium Benzoate and Sodium Phenylacetate can be alternative means of conjugating Ammonium in the body - both can interact with Nitrogen carrying AA and then conjugate and be excreted to get rid of toxic Ammonia
102
In the case of Sodium Benzoate, it can react with ______ which carries an ________ , and can conjugate and be excreted as ______ ______. Then decreasing ammonium levels in body.
Glycine Ammonia (NH3) Hippuric Acid
103
In the case of Sodium Phenylacetate, it can react with _________ and conjugate to be excreted as ____________. Then decreasing ammonium levels in the body.
Glutamine Phenylacetylglutamine
104
What are the two alternative molecules that can help excrete Ammonium from the body besides the Urea cycle?
1. Sodium Benzoate | 2. Sodium Phenylacetate
105
A new born girl appeared normal at birth, but within 24 hours developed lethargy, hypothermia, an apnea. Initial tests showed: low Blood Urea Nitrogen (BUN) Elevated Ammonia High urine orotate Low blood arginine and argininosuccinate Very high Blood citrulline What is the defective enzyme likely to be?
Argininosuccinate synthetase
106
A deficiency in Argininosuccinate synthetase would result in low levels of what two things?
1. Argininosuccinate | 2. Arginine
107
Treatment for those with a Urea Cycle defect often involves an insulin infusion. What is the rationale for this treatment?
The Insulin will inhibit GNG and block L-Alanine catabolism in the skeletal muscle, therefore reducing the influx of NH4 into the Urea cycle
108
Under Fasting conditions, L-Alanine is catabolized from the _______ ______ and will help form the products of ______ and ________. In the case of an insulin infusion treatment, it will block L-Alanine from being catabolized, therefore ________ influx of NH4 into the urea cycle.
skeletal muscle Pyruvate Glutamate (will add NH4 to urea cycle , and convert to Aspartate for Urea cycle) reducing
109
What is the least sever of the Urea cycle deficiencies?
Arginase deficiency
110
``` For Infant 1 with Urea cycle deficiency: Urine Orotate is Low Blood Citrulline is Low Blood Arginine is Low Blood NH3 is High What is the enzyme deficiency? ```
Carbamoyl Phosphate synthetase 1
111
``` For Infant 2 with Urea cycle deficiencies : Urine Orotate not determined Blood Cirtrulline is High (>1000 uM) Blood Arginine is low Blood NH3 is High What is the enzyme deficiency? ```
Argininosuccinate synthetase
112
``` For Infant 3 with Urea Cycle deficiencies: Urine Orotate not determined Blood Citrulline is not determined Blood Arginine is High Blood NH3 is Moerately High What is the enzyme deficiency? ```
Arginase
113
``` For infant 4 with Urea Cycle deficiencies: Urine Orotate is high Blood Citrulline is Low Blood Arginine is Low Blood NH3 is High What is the enzyme deficiency? ```
Ornithine transcarbamoylase (only - X Linked trait)
114
``` For infant 5 with Urea cycle deficiency: Urine Orotate is not determined Blood Citrulline is moderate High (200 uM) Blood Arginine is Low Blood NH3 is High What is the enzyme deficiency? ```
Argininosuccinate lyase
115
In the fasting graph, as the brain starts to use Keytones for energy (B-Hydroxybutyrate and Acetoacetate), there is a _______ in Urinary ______. Prior to this the levels or ketones are increasing parallel to its levels. This is consistent with a decrease in _____ as less substrates are fluxing through the process so less free NH3 to be disposed of.
Drop Ammonia GNG
116
At about how many days of fasting will you see the drop in the graph of Urinary ammonia away from its paralleled increase with Ketone usage?
Day 7-8 | GNG has started to decrease and more reliance on Ketones is established
117
On the fasting graph, Total urinary nitrogen will be _______ when Glucose is high at day Zero, then it will sharply ______ as Glucose does until Glucose stabilizes in the blood and Total Urinary Nitrogen will continue to ______ over the days of fasting.
Elevated Decrease Decrease
118
True or False: Total urinary nitrogen will decrease at the same rate as Urinary ammonia is decreasing in the fasting conditions graph.
False: Total Urinary nitrogen will have a skewed right negative curve decreasing after day 1-2 of fasting , while Urinary Ammonia will continue to increase until day 7-8 parallel with Ketone increases and will start a downward trend after day 7-8 as GNG decreases
119
AA from the diet or protein degradation are either _______ for _____ ______ or deaminated to be used in ______ for energy.
recycled Protein synthesis GNG
120
The single AA that are broken down during digestion are transported into intestinal epithelial cells by ______ and_____ transport.
Active Passive
121
AA catabolism produces Ammonia in the cell that must be transported to the liver as ______ or _______ and used to synthesize _____ as means of disposing of the nitrogen.
Alanine Glutamine Urea
122
The first NH4 will enter the Urea cycle at _______ in the MT.
CPS1
123
The second Nitrogen in the Urea cycle will come from ______ when it conjugates with _____ to form ________.
Aspartate Citrullene Arginosuccinate
124
What are the 4 main treatments for Urea Cycle defects?
1. Glucose/insulin infusion to inhibit Muscle protein breakedown 2. Low protein diet (equals low NH4) 3. Sodium Phenylacetate+Glutamine (Phenylacetylglutamine excretion) 4. Sodium benzoate + Glycine (Hippuric acid excretion)
125
The text notates that ammonia (NH3) and ammonium (NH4) can be used interchangeably , for clarity _____ is used as this is the form in which nitrogen enters the Urea cycle.
Ammonium (NH4)