Nitrogen metabolism Flashcards
(147 cards)
1
Q
Net accumulation of proteins as in growth & pregnancy
A
Positive Nitrogen Balance
2
Q
Net breakdown of protein as in surgery, advanced cancer, kwashiorkor or marasmus, starvation
A
Negative Nitrogen Balance
3
Q
Protein Turnover per day
A
300-400g/day
4
Q
Energy-dependent protein degradation mechanism
A
Ubiquitin-Proteasome Mechanism
5
Q
Protein Degradation: Endogenous
A
Proteasome
6
Q
Protein Degradation: Exogenous
A
Lysosome
7
Q
Sum of all free AAs in cells and ECF, degradation and turnover of body protein, dietary intake, synthesis of non-essential AAs
A
Amino Acid Pool
8
Q
Resorption of Proteins per day
A
150g/day
9
Q
Degradation of Proteins per day
A
50-100g/day
10
Q
Protein Digestion: Stomach
A
HCl, Pepsin
11
Q
Protein Digestion: Pancreatic Enzymes
A
Zymogens activated by Trypsin
12
Q
Protein Digestion: liberate AAs and dipeptides
A
Aminopeptidases
13
Q
Protein Digestion: absorbed by secondary active transport
A
Free AAs
14
Q
Protein Digestion: Endopeptidases
A
Trypsin, Chymotrypsin, Elastase
15
Q
Protein Digestion: Exopeptidases
A
Carboxypeptidase, Aminopeptidase
16
Q
HCl is produced by
A
parietal cells
17
Q
Pepsinogen is produced by
A
chief cells
18
Q
AA Catabolism: removal of the α-amino group (deamination) forming ammonia and a corresponding α-ketoacid
A
First Phase
19
Q
AA Catabolism: carbon skeletons of α-ketoacids are converted to common intermediates of energy-producing metabolic pathways (Glycolysis, Krebs Cycle)
A
Second Phase
20
Q
Major disposal form of nitrogen
A
Urea
21
Q
Nitrogen Excretion: seen in telostean fish, excrete highly toxic ammonia
A
Ammonotelic
22
Q
Nitrogen Excretion: land animals, humans, non-toxic water-soluble urea
A
Ureotelic
23
Q
Nitrogen Excretion: birds, secrete uric acid as semisolid guano
A
Uricotelic
24
Q
Main steps in removing nitrogen from AA
A
transamination, oxidative deamination
25
AA Nitrogen Removal: occurs in all cells of the body, all AAs must transfer their amino groups to α-ketoglutarate to form glutamate (except lysine & threonine)
Transamination
26
Aminotransferases
Alanine Aminotransferase (ALT), Aspartate Aminotransferas (AST)
27
Aminotransferases: Co-Enzyme
Pyridoxal Phosphate (B6)
28
ALT is also known as
SGPT (serum glutamate:pyruvate transferase)
29
ALT/SGPT transaminates
pyruvate, alanine
30
AST is also known as
SGOT (serum glutamate:OAA transferase)
31
AST/SGOT transaminates
aspartate, OAA
32
AA Nitrogen Removal: occurs in the liver and kidney, only for glutamate, glutamate is oxidized and deaminated to yield free ammonia (NH3) which is used to make urea
Oxidative Deamination
33
Oxidative Deamination: Enzyme
Glutamate Dehydrogenase
34
Peripheral Nitrogen Removal: synthesized from glutamate and ammonia, occurs in most tissues, including muscle
Glutamine
35
Peripheral Nitrogen Removal: excess nitrogen from the peripheral tissues can reach the liver through transamination of pyruvate, occurs in muscle
Alanina
36
In the liver, alanine is converted back to pyruvate which may undergo gluconeogenesis which can be transported back to the muscles
Glucose, Alanine Cycle
37
Deaminates glutamine to produce ammonium ion (NH$+) which is excreted from the body, eliminates ammonium ion in the urine (kidneys), ammonium ion sent to the liver via the portal circulation for the urea cycle (SI)
Glutaminase
38
Krebs-Henseleit Cycle/Ornithine Cycle
Urea Cycle
39
Pathway for removal of nitrogenous waste products in the body, present only in the liver, major disposal of amino groups
Urea Cycle
40
Donors of the atoms of urea
NH3 from free ammonia and aspartate, C from CO2
41
Urea Cycle: only _____ can penetrate the mitochondrial membrane
Citrulline
42
Urea Cycle
Ornithine + Carbamoyl Phosphate → Citrulline + Aspartate → Argininosuccinate - Fumarate → Arginine → Urea + Ornithine
43
Urea Cycle: Mitochondrial Reactions
Formation of Carbamoyl Phosphate and Citrulline
44
Urea Cycle: Cytoplasmic Reactions
Synthesis of Arginosuccinate, Cleavage of Arginosuccinate to form Arginine, Arginine cleavage into Urea and Ornithine
45
Urea Cycle Enzymes: Formation of Carbamoyl Phosphate
Carbamoyl Phosphate Synthetase I
46
Urea Cycle Enzymes: Formation of Citrulline
Ornithine Transcarbamoylase
47
Urea Cycle Enzymes: Synthesis of Arginosuccinate
Arginosuccinate Synthetase
48
Urea Cycle Enzymes: Cleavage of Arginosuccinate to form Arginine
Argininosuccinase
49
Urea Cycle Enzymes: Arginine cleavage into Urea and Ornithine
Arginase
50
Urea Cycle: Substrates
NH3, Aspartate, CO2
51
Urea Cycle: Rate-Limiting Step
CO2 + NH3 → Carbamoyl Phosphate
52
Urea Cycle: Rate-Limiting Enzyme
Carbamoyl Phosphate Synthetase I
53
Urea Cycle: Energy Requirement
4 ATP
54
Urea Cycle: Co-Factors
N-acetylglutamate, Biotin
55
Diffuses from the liver and is transported in the blood to the kidneys where it is filtered and excreted in the urine, a portion diffuses from the blood into the intestines and is cleaved to CO2 and NH3 by bacterial urease
Urea
56
Enzyme defect in the urea cycle, hyperammonemia, elevated blood glutamine, decreased BUN, lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, death
Hereditary Hyperammonemia
57
Hereditary Hyperammonemia: Type 1 Defect
Carbamoyl Phosphate Synthetase I Deficiency
58
Hereditary Hyperammonemia: Type 2 Defect
Ornithine Transcarbamoylase Deficiency
59
Hereditary Hyperammonemia: Treatment
low protein diet, administration of Na benzoate or phenylpyruvate to capture and excrete excess nitrogen
60
Compromised liver function, tremors, slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision
Acquired Hyperammonemia
61
Exclusively ketogenic AAs
Leucine, Lysine
62
Ketogenic and Glucogenic AAs
Phenylalanine, Tyrosine, Tryptophan, Isoleucine
63
Ketogenic AAs yield
acetoacetate, acetyl-CoA/acetoacetyl-CoA
64
Glucogenic AAs yield
Pyruvate, intermediates of the Krebs Cycle
65
AAs that enter the Krebs Cycle via α-ketoglutarate
Glutamine, Glutamate, Proline, Arginine, Histidine
66
AAs that enter the Krebs Cycle via Pyruvate
Alanine, Serine, Glycine, Cysteine, Threonine, Tryptophan
67
AAs that enter the Krebs Cycle via Fumarate
Phenylalanine, Tyrosine
68
AAs that enter the Krebs Cycle via Succinyl-CoA
Methionine, Valine, Isoleucine, Threonine
69
AAs that enter the Krebs Cycle via Oxaloacetate
Aspartate, Asparagine
70
AAs synthesized from transamination of α-ketoacids
Alanine, Aspartate, Glutamate
71
AAs synthesized from amidation of Glutamate and Aspartate
Glutamine, Asparagine
72
AA synthesized from Glutamate
Proline
73
AA synthesized from Methionine and Serine
Cysteine
74
AA synthesized from 3-phosphoglycerate
Serine
75
AA synthesized from Serine
Glycine
76
AA synthesized from Phenylalanine
Tyrosine
77
AA synthesized into heme, purines, creatine, conjugated to bile acids
Glycine
78
AA synthesized into phospholipid, sphingolipid, purines, thymine
Serine
79
AA synthesized into GABA
Glutamate
80
AA synthesized into thioethanolamine of CoA, taurine
Cysteine
81
AA synthesized into histamine
Histidine
82
AA synthesized into creatinine, polyamines, NO
Arginine
83
AA synthesized into serotonin, NAD, NADP, melatonin
Tryptophan
84
AA synthesized into catecholamine, thyroid hormones (T3 & T4), melanin
Tyrosine
85
Deficiency in phenylalanine hydroxylase or tetrahydrobiopterine cofactor, tyrosine becomes essential, phenylalanine builds up, excess phenylketones (phenylacetate, phenyllactate, phenylpyruvate)
Phenylketonuria
86
Mental retardation, growth retardation, fair skin, eczema, musty body odor
Phenylketonuria
87
Phenylketonuria: Treatment
decrease phynylalanine and increase tyrosine in diet
88
Congenital deficiency of homogentistic acid oxidase in the degradative pathway of tyrosine, alkapton bodies cause urine to turn to black on standing, connective tissue is dark (ochronosis), benign, may have debilitating arthralgias, pigmentation of the sclera (Osler's Sign)
Alkaptonuria
89
Congenital deficiency in Tyrosinase or Tyrosine Transporters, lack of melanin leads to increased risk of skin cancer, can result from a lack of migration of neural crest cells
Albinism
90
Albinism: inability to synthesize melanin from tyrosine, autosomal recessive
Tyrosinase Deficiency
91
Albinism: decreased amounts of tyrosine and thus melanin
Defective Tyrosine Transporters
92
Autosomal recessive, cystathionine synthase deficiency, decreased affinity of cystathione synthase for pyridoxal phosphate, homocysteine methyltransferase deficiency, excess homocysteine, cysteine becomes essential
Homocystinuria
93
Treatment for cystathionine synthase deficiency
decrease methionine, increase cysteine, B6 and folate in the diet
94
Treatment for decreased affinity of cystathione synthase for pyridoxal phosphate
increase B6 in the diet
95
Mental retardation, osteoporosis, tall, kyphosis, lens subluxation (downward, inward), atherosclerosis, stroke, MI
Homocystinuria
96
Common inherited defect of renal tubular AA transporter for cystine, ornithine, lysine and arginine in the PCT of the kidneys, excess cystine in the urine leads to cystine stones (staghorn calculi)
Cystinuria
97
Cystinuria: Treatment
Acetazolamide (alkalinize the urine)
98
Kidney Stones in Acidic Urine
uric acid, cystine
99
Kidney Stones in Alkaline Urine
magnesium alkaline phosphate (struvite) from urease producing bacteria (Proteus)
100
Blocked degradation of branched AA (Valine, Isoleucine, Leucine) due to a deficiency in α-ketoacid dehydrogenase, causes increased α-ketoacid in the blood (esp. leucine), severe CNS defects, mental retardation, death
Maple Syrup Urine Disease
101
Cyclic compounds formed from the linkage of four pyrrole rings through methyne (-HC) bridges, form complexes with metal ions bound to nitrogen atom of the pyrrole rings
Porphyrins
102
The heme of hemoglobin contains
iron
103
The heme of chlorophyll contains
magnesium
104
Heme synthesis is present in
all tissues
105
Used in hemoglobin, myoglobin, cytochromes, catalase, peroxidase, guanylate cyclase
heme
106
The initial and the last three steps in the formation of porphyrins occur in
mitochondria
107
The intermediate steps occur in the
cytosol
108
Steps in Heme Synthesis
Formation of δ-aminolevulinic acid, porphobilinogen, uroporphobilinogen, heme
109
Heme Synthesis: Rate-Limiting Step
Glycine + Succinyl CoA → δ-Aminolevulinic Acid
110
Heme Synthesis: Rate-Limiting Enzyme
ALA Synthase
111
Heme Synthesis: ALA Synthase Co-Factor
Pyridoxine (B6)
112
Heme Synthesis: condensation of two molecules of ALA by zinc-containing ALA Dehydratase, inhibited by heavy metal ions (lead) that replace the zinc
Formation of Porphobilinogen
113
Introduction of iron (Fe3+) into protoporphyrin IX occurs spontaneously but the rate is enhanced by ferrochelatase, also inhibited by lead
Formation of Heme
114
Genetic or acquired disorders due to abnormalities in the pathway of biosynthesis of heme, erythropoietic or hepatic
Porphyrias
115
Most Common Porphyria
Porphyria Cutanea Tarda
116
Photosensitivity or chronic inflammation to overt blistering and shearing in sun-exposed areas, abdominal pain (after ring, step 5 onwards), neuropsychiatric symptoms (before ring)
Porphyria
117
Pyridoxine deficiency associated with Isoniazid therapy
Sideroblastic Anemia (ringed sideroblasts)
118
Heme synthase (ferrochelatase) introduces the Fe2+ into protoporphyrin IX to make the heme ring, microcytic, hypochromic anemia
Iron Deficiency
119
Inactivates many enzymes in heme synthesis (ALA dehydratase, ferrochelatase)
Lead Poisoning
120
Coarse basophilic stippling of RBC, headache, memory loss, peripheral neuropathy, claw hand, wrist-drop, nausea, abdominal pain, diarrhea, lead lines in gums, deposits in epiphyses, increase urinary ALA and free erythrocyte porphyrin
Lead Poisoning
121
Causes microcytic, hypochromic anemia
IDA, Thalassemia, Lead Poisoning
122
Causes megaloblastic anemia
Folate/B12 Deficiency, Pernicious Anemia
123
Causes normocytic, normochromic anemia
blood loss, chronic disease, CKD
124
Causes increased MCHC
Hereditary Spherocytosis
125
ALA synthase deficiency, anemia, decreased red cell counts and Hgb
X-linked Sideroblastic Anemia
126
Abdominal pain, neuropsychiatric, urinary δ-aminolevulinic acid
ALA Dehydratase Deficiency
127
Uroporphyrinogen I synthase deficiency, abdominal pain, neuropsychiatric, urinary porphobilinogen (+), uroporphyrin (+)
Acute Intermittent Porphyria
128
Uroporphyrinogen III synthase deficiency, no photosensitivity, urinary porphobilinogen (-), uroporphyrin (+)
Congenital Erythropoietic Porphyria
129
Uroporphyrinogen decarboxylase deficiency, photosensitivity, urinary porphobilinogen (-), uroporphyrin (+)
Porphyria Cutanea Tarda
130
Coproporphyrinogen oxidase deficiency, photosensitivity, abdominal pain, neuropsychiatric, urinary porphobilinogen (+), uroporphyrin (+), fecal protoporphyrin (+)
Hereditary Coproporphyria
131
Protoporphyrinogen oxidase deficiency, photosensitivity, abdominal pain, neuropsychiatric, urinary porphobilinogen (+), fecal protoporphyrin (+)
Variegate Porphyria
132
Ferrochelatase deficiency, photosensitivity, fecal protoporphyrin (+), red cell protoporphyrin (+)
Protoporphyria
133
After 120 days, RBCs are taken up and degraded by the
reticuloendothelial system (liver, spleen)
134
Heme Degradation
formation of bilirubin → uptake of bilirubin by the liver → formation of bilirubin diclucoronide → secretion of bilirubin into bile → formation of urobilins in the intestine
135
Reactions of heme oxygenase in reticuloendothelial cells
heme → biliverdin (green) → bilirubin (red orange)
136
Bilirubin transported to the liver by binding to
albumin
137
In the liver, bilirubin binds to intracellular proteins particularly
ligandin
138
Bilirubin is conjugated to two molecules of glucuronic acid by
Bilirubin Glucuronyltransferase
139
Bilirubin Glucuronyltransferase Deficiency
Crigler-Najjar I and II, Gilbert Syndrome
140
Transported into the bile canaliculi and then into the bile, susceptible to impairment in liver disease
Bilirubin Diglucuronide
141
In the gut, bilirubin is converted into a colorless substance
urobilinogen
142
Intestinal bacteria oxidize urobilinogen into
stercobilin (brown)
143
Some urobilinogen is reabsorbed from the blood and enters the
portal circulation
144
Remaining urobilinogen is transported by the blood to the kidney where it is converted to
urobilin (yellow)
145
Jaundice: hemolytic anemias, neonatal physiologic jaundice, Crigler-Najjar I and II, Gilbert syndrome, toxic hyperbilirubinemia
Unconjugated Hyperbilirubinemia
146
Jaundice: biliary tree obstruction, Dubin-Johnson syndrome, Rotor Syndrome
Conjugated Hyperbilirubinemia
147
Used to measure total and direct bilirubin
Van den Bergh Reaction
