Endo: Catabolism Of Proteins & AA Nitrogen Flashcards
(139 cards)
0
Q
An excess of ingested over excreted nitrogen.
A
Positive nitrogen balance
1
Q
Protein and AA catabolism described how
A
Nitrogen is converted to urea
2
Q
Positive nitrogen balance accompanies
A
Growth and pregnancy
3
Q
Nitrogen Output exceeds intake
A
Negative nitrogen balance
4
Q
Negative nitrogen balance accompanies
A
Surgery, Advanced cancer & Marasmus/Kwashiorkor “SAM K”
5
Q
Ammonia, derived mainly from _______, is highly toxic, tissues covert ammonia to _______ of nontoxic glutamine.
A
a-amino nitrogen of AAs. Amide nitrogen.
6
Q
Subsequent deamination of glutamine in the liver releases ammonia, which is then converted to
A
Nontoxic Urea
7
Q
Liver function is compromised in this disease states, elevated ammonia levels generate clinical s/sx
A
Cirrhosis or Hepatitis
8
Q
_______ turnover occurs in all forms of life.
A
Protein
9
Q
Each day, humans turn over ____% of their total body protein. Principally __________.
A
1-2%. Muscle protein.
10
Q
High rates of protein degradation occur in tissue undergoing structural rearrangement such as
A
Uterine tissue during pregnancy
11
Q
Of the liberated AAs, approximately __% are reutilized
A
75%
12
Q
Excess of nitrogen forms
A
Urea
13
Q
Since excess AAs are not stored , those not immediately incorporated into new protein are
A
Rapidly degraded
14
Q
Degrade protein to AAs
A
Proteases & Peptidases
15
Q
The susceptibility of a protein to degradation is expressed as its
A
Half life
16
Q
Half lives of liver proteins range from
A
Under 30mins- over 150hrs
17
Q
Typical housekeeping enzymes have a half
Iife values of over
A
100hrs
18
Q
Key regulatory enzymes have a half life of
A
0.5-2hrs
19
Q
Target some proteins for rapid degradation
A
PEST sequence: Proline, Glutamate, Serine & Threonine
20
Q
Resulting peptides are then degraded to AAs by ______ that cleave internal bonds.
A
Endopeptidases
21
Q
Remove AAs sequentially from the amino terminals
A
Aminopeptidases
22
Q
Remove AAs sequentially from the carboxy terminals
A
Carboxypeptidases
23
Q
Extracellular, membrane associated and long lived intracellular proteins are degraded in _______ by __________.
A
Lysosomes. ATP-independent processes.
24
Degradation of abnormal and other short-lived proteins occur in ______ and requires ____ & _______.
Cytosol. ATP & Ubiquitin.
25
Is a small(8.5 kDa) proteinthat targets many intracellular proteins for degradation. The primary structure of this is highly conserved. Only _____ residues differ between yeast and human.
Ubiquitin. 3 of 76.
26
Several molecules of ubiquitin are attached by nonpetide bonds formed between the
Carboxy terminal of ubiquitin & amino groups of lysyl residues
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The terminal of COOH of ubiquitin forms a ________ bond with an -SH of E1 in a reaction driven by conversion of ___ to ___ and ___. Subsequent hydrolysis of PPi by ________ ensures that reaction 1 will proceed readily.
Thioester. ATP. AMP & PPi. Pyrophosphate.
28
A thioester exchange reaction transfers activated ubiquitin to __.
E2
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Catalyzes transfer of ubiquitin to amino group of lysyl residues of target proteins.
E3
30
Affects whether a protein is ubitiquinated
Residue present at its amino terminal
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Amino terminal that retards ubiquitination
Met or Ser
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Amino terminal that accelerates ubiquitination
Asp or Arg
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Degradation occurs in a multicalytic complex of proteases known as
Proteasome
34
Proteins are hydrolyzed to this for absorption to make them smaller
AAs
35
Proteolytic enzymes responsible for degrading proteins are in the
Stomach, pancreas & small intestine
36
Contains gastric juices HCL and pepsin
Stomach
37
Kills bacteria
HCl
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Is from pepsinogen which is activated by HCl
Pepsin
39
Further cleave polypeptides initially digested by the stomach
Pancreatic proteases
40
From the intestine activates pancreatic enzymes such as ________ to its active form.
Enteropeptidase. Trypsinogen.
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Small intestine contains _______ that cleaves oligopeptides to produce ________.
Aminopeptidases. Free AAs.
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Absorbed by the intestinal epithelium
Free amino acids and dipeptides
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Dipeptides are further hydrolyzed in the _______ before being released to the portal system.
Cytosol
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Excrete ammonia
Ammonotelic
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Excrete uric acid
Uricotelic
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Ammonotelic in nature, compels them to excrete water continuously, facilitating excretion of highly toxic ammonia.
Teleostean fish
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Must conserve water and maintain low weight, uricotelic in nature and excrete uric acid as ___________.
Birds. Semisolid guano.
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Many land animals, including humans, are _______ and excrete nontoxic, water-soluble urea
Ureotelic
49
A consequence- not a cause- of impaired renal function
High blood urea levels
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4 stages in Urea biosynthesis
-Transamination
-Oxidative deamination of glutamate
-Ammonia transport
-Reactions of the urea cycle
"TOAR"
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Transfers a-Amino Nitrogen to a-Ketoglutarate, forming Glutamate. Reaction is readily reversible.
Transamination
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Transamination interconverts pairs of
a-amino acids & a-keto acids
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Do not participate in transamination
Proline, Hydroxyproline, Lysine & Threonine
54
Also function in amino acid biosynthesis
Aminotransferases
55
A coenzyme present at the catalytic site of aminotransferases and of many other enzymes that act on AAs
Pyridoxal Phosphate
56
During transamination, bound ____ serves as a carrier of amino groups. Following removal of a-amino nitrogen by transamination, the remaining carbon skeleton is _________.
PLP. Degraded.
57
2 enzymes that catalyze the transfer of amino groups to pyruvate(forming ______) or to a-ketoglutarate(forming ____)
Alanine pyruvate aminotransferase(alanine aminotransferase) & glutamate-a-ketoglutarate aminotransferase(glutamate aminotransferase)
Alanine. Glutamate.
58
Each aminotransferase is specific for _____ of substrates but nonspecific for other pair.
One pair
59
Since alanine is also a substrate for ____________, all the amino nitrogen from amino acids that undergo transamination can be concentrated in __________.
Glutamate aminotransferase. Glutamate.
60
Is the only AA that undergoes oxidative deamination at an appreciable rate in mammalian tissues.
L-glutamate
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The formation of ammonia from a-amino groups thus occurs mainly via
A-amino nitrogen of L-glutamate
62
Occupies a central position in nitrogen metabolism
L-glutamate dehydrogenase
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Transfer of amino nitrogen to a-ketoglutarate forms
L-glutamate
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Release of this nitrogen as ammonia is then catalyzed by hepatic ______________, which can either use ___ or ____.
L-glutamate dehydrogenase. NADP NADH
65
Conversion of a-amino nitrogen to ammonia by the concerted action of glutamate aminotransferase and GDH is often termed
Transdeamination
66
Liver GDH is allosterically inhibited by
ATP, GTP & NADH
67
Liver GDH is allosterically activated by
ADP
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Reaction catalyzed by ____ is freely reversible and functions also in AA biosynthesis
GDH
69
Also remove nitrogen as ammonia
Amino acid oxidases
70
Convert AAs to an a-amino acid that decomposes to an a-ketoacid with release of ammonium ion.
L-amino acid oxidase
71
The reduced _____ is reoxidized by molecular oxygen , forming hydrogen peroxide, which then is split to ___ & ___ by ________.
Flavin. O2 & H2O. Catalase.
72
Is life threatening
Ammonia intoxication
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The ammonia produced by enteric bacteria and absorbed into portal venous blood and the ammonia produced by tissues are rapidly removed from the circulation by the _____ and converted ____.
Liver. Urea.
74
Percent of ammonia always present in peripheral blood
10-20g/dL
75
Toxic to the CNS
Ammonia
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Symptoms of ammonia intoxication
Tremors, slurred speech, blurred vision, coma & death "TSB CD"
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Ammonia may be toxic to the brain in part because it reacts with _________ to form _______.
a-ketoglutarate. Glutamate.
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Resulting depleted levels of a-ketoglutarate then impair function of the
Tricarboxylic acid(TCA) in neurons
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Catalyzed the formation of glutamine and fixes ammonia as glutamine.
Glutamine synthase
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Since amide bond synthesis is coupled to the hydrolysis of __ to ___ and ____, the reaction strongly favors glutamine synthesis.
ATP. ADP & Pi.
81
Sequester ammonia in a no toxic form.
Glutamine
82
Strongly favors glutamate formation. Catalyze the hydrolytic release of the amide nitrogen of glutamine as ammonia.
Glutaminase
83
Catalyzes the interconversion of free ammonium ion and glutamine. An analogous reaction is catalyzed by _________.
Glutamine synthase & Glutaminase. L-Asparaginase.
84
Formation & secretion of this maintains acid base balance
Ammonia
85
Facilitates cation conservation and regulation of acid base balance. Produced by _________.
Excretion into urine of ammonia. Renal tubular cells.
86
Ammonia production from intracellular renal AAs, especially glutamine, increases in
Metabolic acidosis
87
Ammonia production from intracellular renal AAs, especially glutamine, decreases in
Metabolic alkalosis
88
Series of reactions that produce urea from ammonia (NH3). In mammals this cycle occurs in the _____.
Urea/Ornithine cycle. Liver.
89
Urea cycle was first discovered by
Krebs & Kurt Henseleit, 1932
90
Organisms that cannot easily and quickly remove ammonia usually have to convert it to some other substance, like ___ or ____, which are much less toxic.
Urea. Uric acid.
91
Result of liver failure is the accumulation of nitrogenous waste , mainly ammonia, which leads to a neuropsychiatric abnormality
Hepatic encephalopathy
92
The urea cycle consists of five reactions.
2 mitochondrial, 3 cytosolic
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Urea cycle: converts two amino groups, one from NH4 and one from Asp, and a carbon atom from HCO3, to relatively nontoxic excretion product, urea at the cost of four high energy phosphate bonds _____ hydrolyzed to ____ & ____.
3 ATP. 2 ADP. 1 AMP.
94
Is the carrier of the urea cycle carbon and nitrogen atoms
Ornithine
95
Major end product of nitrogen catabolism in humans
Urea
96
Synthesis of 1 mol of urea requires ______ plus ______ and _____________.
3mol of ATP. 1 mol of each ammonium ion. a-amino nitrogen of aspartate.
97
Initiates urea biosynthesis
Carbamoyl Phosphate Synthase
98
Rate limiting enzyme of the urea cycle. Condensation of CO2, ammonia and ATP to form carbamoyl phosphate is catalyzed by mitochondrial
Carbamoyl Phosphate Synthase I
99
An allosteric activator of carbamoyl phosphate synthase I. Enhances the affinity of the synthase for ATP.
N-acetylglutamate
100
Formation of carbamoyl phosphate requires ________.
2mol of ATP
101
Defect in the enzyme carbamoyl phosphate synthase
Hyperammonenia type I
102
Carbamoyl phosphate plus ornithine forms
Citrulline
103
Catalyze transfer of the carbamoyl group of carbamoyl phosphate to ornithine, forming _____ and ______. Reaction occurs in the _______.
L-Ornithine transcarbamoylase. Citrulline & orthophosphate. Mitochondrial matrix.
104
Results from mutation of the ORNT1 gene that encoded the mitochondrial membrane ornithine transporter.
Hyperornithinemia, hyperammonemia and homocitrullinuria "HHH syndrome"
105
Failure to import cytosolic ornithine into the mitochondrial matrix renders the ________ inoperable.
Urea cycle
106
Citrulline olus aspartate forms
Argininosuccinate
107
Links aspartate and citrulline via the amino group of aspartate and provides the second nitrogen of urea. The reaction requires ___.
Argininosuccinate synthase
108
Subsequent displacement of AMP by aspartate forms
Citrulline
109
Cleavage of Argininosuccinate forms
Arginine & Fumarate
110
Cleavage of argininosuccinate, catalyzed by ______, proceeds with retention of nitrogen in ______ and release of the aspartate as _______.
Argininosuccinase. Arginine. Fumarate.
111
Fumarate is recycled back to
Aspartate
112
Addition of water to fumarate forms ________ and subsequent NAD+dependent oxidation of malate forms ________. Analogous to reactions of the citric acid cycle but are catalyzed by __________ & ___________.
L-malate. Oxaloacetate. Cytosolic fumarase & malate dehydrogenase.
113
Transamination of oxaloacetate by ________ then re forms ______.
Glutamate aminotransferase. Aspartate.
114
Arginine is produced from
Argininosuccinate
115
ASL gene is located on chromosome
7
116
Deficiency in argininosuccinase which is accompanied by elevated levels of argininosuccinate in blood, CSF and urine.
Argininosucciniaciduria
117
Argininosucciniaciduria is associated with friable & tufted hair
Trichorrhexis nodosa
118
Cleavage of arginine releases ____ & Re forms ____.
Urea. Ornithine.
119
Hydrolytic cleavage of the guanidino group of arginine, catalyzed by liver ______, releases _____.
Arginase. Urea.
120
Re enters liver mitochondria for additional rounds of urea synthesis.
Ornithine
121
Are potent inhibitors of arginase, competitive with arginine.
Ornithine & Lysine
122
Arginine also serves as the precursor of the potent muscle relaxant __________ and catalyzed by ___________.
Nitric oxide. Nitric oxide synthase.
123
Is an autosomal recessive defect in the gene for arginase. Symptoms of this appear until age __ to __ years.
Hyperargininemia. 2-4
124
Is the pacemaker enzyme of the urea cycle
Carbamoyl Phosphate Synthase I
125
The activity of carbamoyl phosphate synthase I is determined an allosteric activator
N-acetylglutamate
126
N-acetylglutamate level is dictated by its rate of synthesis from _____ & ______ and its rate of hydrolysis to ______ & _______. These reactions are catalyzed by __________ & _________
Acetyl CoA & Glutamate. Acetate & Glutamate. N-acetylglutamate synthase & hydrolase.
127
Defects in NAGS gene result in
Hyperammonemia
128
Elevate enzyme levels to cope with the increased production of ammonia
Starvation
129
All defects in urea synthesis results in
Ammonia intoxication
130
The effects are more severe when the metabolic block occurs at reactions
1 or 2
131
Clinical symptoms common to all urea cycle disorders include
Vomiting, avoidance of high protein foods, intermittent ataxia, irritability, lethargy and severe mental retardation
132
Significant improvement and minimization of brain damage accompanies
Low CHON diet & Small frequent meals
133
Offers promise for correcting defects in urea biosynthesis
Gene therapy
134
2ATP+HCO3+NH4. Name product, Enzyme and Location
Carbamoyl phosphate. Carbamoyl phosphate synthase. Mitochondria.m
135
Carbomoyl phosphate+ornithine. Name product, Enzyme and Location
Citrulline. Ornithine transcarbamoylase. Mitochondria.
136
Citrulline+aspartate+ATP. Name product, Enzyme and Location
Argininosuccinate. Argininosuccinate synthase. Cytosol.
137
Argininosuccinate. Name product, Enzyme and Location
Arg+fumarate. Argininosuccinate lyase. Cytosol.
138
Arg+H2O. Name product, Enzyme and Location
Ornithine+urea. Arginase. Cytosol.
