V - Proteins Flashcards
(339 cards)
1
Q
Most abundant and functionally diverse molecules in living systems
A
proteins
2
Q
Linear polymers if amino acids
A
proteins
3
Q
Set of all the proteins expressed by an individual cell at a particular time
A
proteome
4
Q
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
A
Proteomics
5
Q
Aims to identify proteins and their post-translational modifications whose appearance or disappearance correlates with physiologic phenomena, aging or specific diseases
A
Proteomics
6
Q
There are more than 300 amino acids but only ___ are commonly found in mammalian proteins,
A
20
7
Q
All amino acids have _____, _____ & _____ except for _____.
A
carboxyl group (-COOH), amino group (-NH2), unique side chain (R-group), proline
8
Q
All three molecular groups in an amino acid are bonded to a central
A
α-carbon
9
Q
Dictates the function of the amino acid in a protein
A
R-group
10
Q
Amino Acids: Alipathic Side Chains
A
Glycine, Alanine, Valine, Leucine, Isoleucine
11
Q
Amino Acids: Hydroxylic Groups
A
Serine, Threonine, Tyrosine
12
Q
Amino Acids: Sulfur Atoms
A
Cysteine, Methionine
13
Q
Amino Acids: Aromatic Side Chains
A
Histidine, Phenylalanine, Tyrosine, Tryptophan
14
Q
Imino Acid
A
Proline
15
Q
Amino Acids: Basic Groups
A
Lysine, Arginine, Histidine
16
Q
Amino Acids: Acidic Groups
A
Aspartic acid, Asparagine, Glutamic acid, Glutamine
17
Q
Side Chains: net charge of zero at physiologic pH, promote hydrophobic interactions, cluster in the interior of the protein
A
non-polar side chains
18
Q
Amino Acids: has the smallest side chain, used in the first step of heme synthesis, used in purine synthesis, major inhibitory neurotransmitter in the spinal cord
A
Glycine
19
Q
Glycine + Succinyl CoA
A
δ-ALA (aminolevulinic acid)
20
Q
Amino Acids: Amino Acids: Carries nitrogen from peripheral tissues to the liver
A
Alanine
21
Q
Amino Acids: branched-chain amino acids whose metabolites accumulate in Maple Syrup Urine Disease (deficiency in branched-chain α-ketoacid dehydrogenase)
A
Valine, Isoleucine, Leucine
22
Q
Amino Acids: accumulates in Phenylketonuria
A
Phenylalanine
23
Q
Deficient enzyme in PKU
A
Phenylalanine Hydroxylase
24
Q
Accumulating metabolites in PKU
A
phenyllactate, phenylpyruvate, phenylacetate
25
Causes the musty odor in PKU
phenylacetate
26
Amino Acids: has the largest side chain, precursor for niacin, serotonin (5-HT) and melatonin
Tryptophan
27
Amino Acids: precursor of homocysteine
Methionine
28
Methionine is used in transfer of methyl groups as
S-adenosylmethionine (SAM)
29
Amino Acids: contributes to the fibrous structure of collagen and interrupts α-helices in globular proteins
Proline
30
Side Chains: zero net charge at physiologic pH, presence of side chains that can participate in hydrogen bonds
uncharged polar side chains
31
Amino Acids: contains a sulfhydryl group that is an active part of many enzymes
Cysteine
32
2 cysteine molecules connected by a covalent disulfide bond, abundant in keratin
Cystine
33
Products from Phenylalanine
Phenylalanine → Tyrosine → L-Dopa → Dopamine → Norepinephrine → Epinephrine
34
Precursor for thyroxine and melanin
Tyrosine
35
Amino Acids: phosphorylation site of enzyme modification, linked to carbohydrate groups in glycoproteins
Serine
36
Amino Acids: sites for O-linked glycosylation in the golgi apparatus
Serine, Threonine
37
Amino Acids: have a carbonyl group and an amide group that can also form hydrogen bonds
Asparagine, Glutamine
38
Amino Acids: site for N-linked glycosylation in the endoplasmic reticulum
Asparagine
39
Amino Acids: deaminated by glutaminase resulting in the formation of ammonia, major carrier of nitrogen to the liver from the peripheral tissues
Glutamine
40
Side Chains: negatively charged at physiologic pH because of the carboxylate group, participate in ionic reactions
acidic side chains
41
Amino Acids: precursor for GABA and glutathione
Glutamate
42
Side Chains: positively charged because of the amine group
basic side chains
43
At neutral pH, arginine and lysine are
positively charged
44
At neutral pH, histidine is
neutral (weak base)
45
Amino Acids: precursor of histamine, used in the diagnosis of folic acid deficiency
Histidine
46
Ingividuals deficient in folic acid excrete increased amounts of FIGlu in urine particularly after ingestion of large doses of histidine
N-formiminoglutamate Excretion Test
47
Amino Acids: precursor of creatinine, urea and nitric oxide
Arginine
48
21st Amino Acid
Selenocysteine
49
Amino Acids: found in a handful of proteins, including certain peroxidases and reductases, inserted into polypeptides during translation but is not specified by a simple three-letter codon, a selenium atom replaces the sulfur in cysteine
Selenocysteine
50
Non-Polar Amino Acids
Glycine, Alanine, Leucine, Isoleucine, Valine, Phenylalanine, Tryptophan, Methionine, Proline
51
Polar Uncharged Amino Acids
-OH (Serine, Threonine, Tyrosine), -SH (Cysteine), Amide (Asparagine, Glutamine)
52
Charged Amino Acids
Acidic (Aspatrate, Glutamate), Basic (Lysine, Arginine, Histidine)
53
All amino acids are chiral except for
Glycine
54
An atom in a molecule that is bonded to 4 different chemical species allowing for optical isomerism
chiral center
55
Molecuels that are exact mirror images of each other
Stereoisomers/Enentiomers/Optical Isomers
56
Most common configuration of AAs
L-configuration
57
A chemical compound that has a total net charge of zero
Zwitterion
58
pH where the zwitterion predominates (AA is uncharged)
Isoelectric Point (pI)
59
Isoelectric Point (pI)
(pKa before + pKa after)/2
60
Molecular group that accepts protons
amino group
61
Molecular group that donates protons
carboxylic acid group
62
AAs that cannot be synthesized by the body and must come from the diet
Phenylalanine, Valine, Tryptophan, Threonine, Histidine, Arginine, Leucine, Lysine
63
Conditionally Non-Essential AAs: may be made in the body but usually not enough
Arginine
64
Conditionally Non-Essential AAs: may be recycled but should eventually be consumed since it is not made at all
Histidine
65
Linear sequence of a protein's amino acids
Primary Structure
66
Attaches α-amino group of ne AA to the α-carbonyl group of another, very stable, can only be disrupted by hydrolysis through prolonged exposure to a strong acid or base at elevated temperatures, polar, can form hydrogen bonds
Peptide Bonds
67
Makes the peptide bond rigid and planar
partial double bond
68
Cleaves the N-terminal amino acid
Sanger's reagent, Edman's reagent
69
Cleaves the C-terminal amino acid
Hydrazine, Carboxypeptidase
70
Used to detect covalent modifications in proteins
mass spectrometry
71
The folding of short (3-30 residues) contiguous segments of polypeptide into geometrically ordered units, regular arrangements of AA that are located near each other in the linear sequence, stabilized by excessive hydrogen bonding
Secondary Structure
72
Secondary Structures: most common, R-handed spiral with polypeptide back bone core, side chains extend outward, 3.6 AA per turn of the spiral
Alpha Helix
73
Alpha helices are disrupted by
proline, large R-groups, charged R-groups
74
Secondary Structures: surfaces appear flat and pleated, 2 or more peptide chains parallel to each other, interchain and intrachain bonds
Beta Sheet
75
Secondary Structures: combinations of adjacent secondary structures such as β-α-β unit, Greek key, β-meander, β-barrel
Motifs (Supersecondary Structures)
76
Secondary Structures: R-handed spiral, H-bonds parallel to helix, keratin, hemoglobin
Alpha Helix
77
Secondary Structures: sheets, H-bonds perpendicular to sheets, amyloid, immunoglobulin
Beta-Pleated Sheet
78
Overall 3D shape of the protein, globular, fibrous, refers to the folding of domains and their final arrangement in the polypeptide
Tertiary Structure
79
The tertiary structure of proteins are stabilized by
disulfide bonds, hydrophobic interactions, hydrogen bonds, ionic bonds
80
Fundamental functional and 3D structural units of a polypeptide, formed by combinations of motifs
Domains
81
Specialized group of group of proteins required for the proper folding of many species of proteins, prevent aggregation, thus providing an opportunity for the formation of appropriate secondary structural elements and their subsequent coalescence into a molten globule
Chaperones
82
Can rescue proteins that have become thermodynamically trapped in a misfolded dead end by unfolding hydrophobic regions
Chaperones
83
Structure of proteins consisting of more than one polypeptide chain, held together by non-covalent bonds
Quarternary Structure
84
Precipitation of a protein so that it forms ordered crystals that can diffract x-rays
X-ray Crystallography
85
Measures the absorbency of radiofrequency electromagnetic energy by certain atomic nuclei, groups of nuclei have particular absorbency patterns
Nuclear Magnetic Resonance Spectroscopy
86
Molecular dynamics programs can be used to stimulate the conformational dynamics of a protein and the manner in which factors such as temerature, pH, ionic strongth or AA amino acid substitutions influence these motions
Molecular Modeling
87
Disruption of a protein's structure
Denaturation
88
Means of Protein Denaturation
heat, organic solvents, mechanical mixing, strong acids or bases, detergents, ions of heavy metals (lead & mercury)
89
Fatal neurodegenerative diseases characterized by spongiform changes, astrocytic gliomas and neuronal loss resulting from the deposition of insoluble protein aggregates in neural cells
Prion Diseases
90
Prions: normal protein, rich in α-helices
PrPc
91
Prions: pathologic conformation, rich in β-sheets
PrPsc
92
The caharcteristic senile plaques and neurofibrillary bundles of the protein β-amyloid which undergoes conformational transformation from a soluble α-helix rich state rich in β-sheets and prone ti self aggregation, mediated by Apo-E
Alzheimer's Disease
93
A complex of protoporphyrin IX and ferrous iron (Fe2+), electron carrier in cytochromes, active site of the enzyme catalase that breaks down hydrogen peroxide, reversibly binds oxygen in myoglobin and hemoglobin
Heme
94
Heme protein found exclusively in red blood cells, composed of heme and 4 globin chains
Hemoglobin
95
Major transporter of CO2 in the blood
HCO3 (75%), carbaminohemoglobin (25%)
96
Hemoglobin: ζ2ε2, conception until the first few months, yolk sac
Embryonal Hemoglobin (Gower 1)
97
Hemoglobin: α2γ2, first few months to after birth, liver
Fetal Hemoglobin (HbF)
98
Hemoglobin: α2γ2, 8th month onwards, marrow
Hemoglobin A (HbA)
99
Hemoglobin: α2δ2, shortly after birth onwards, marrow
Hemoglobin A2 (HbA2)
100
Binds up to 4 molecules of oxygen, exhibits positive cooperativity, sigmoidal curve
Hemoglobin
101
Hemoglobin binds to O2 with increasing affinity
Positive Cooperativity
102
Hemoglobin: low oxygen affunity
T (taut)
103
Hemoglobin: high oxygen affinity (300x)
R (relaxed)
104
Heme protein found in the heart and skeletal muscles, reservoir of oxygen, oxygen carrier that increases the rate of transport of O2 within the muscle cell, hyperbolic curve
Myoglobin
105
Consists of a single polypeptide chain composed of polar and non-polar AAs, contains histidine for O2 binding, released from damaged muscle fibers and turns the urine dark red, can be detected in plasma following MI
Myoglobin
106
O2 Carriers: 1 polypeptide
Myoglobin
107
O2 Carriers: carries 1 O2
Myoglobin
108
O2 Carriers: hyperbolic curve (saturation)
Myoglobin
109
O2 Carriers: storage
Myoglobin
110
O2 Carriers: heart, muscle
Myoglobin
111
O2 Carriers: 4 polypeptides
Hemoglobin
112
O2 Carriers: carries 4 O2
Hemoglobin
113
O2 Carriers: sigmoidal curve (cooperativity)
Hemoglobin
114
O2 Carriers: transport
Hemoglobin
115
O2 Carriers: allosteric effects are present
Hemoglobin
116
Factors whose interaction with one site of the hemoglobin affects the binding of oxygen to heme groups at other locations, effect may be positive or negative, myoglobin is not affected
Allosteric Effectors
117
Shifts the O2 Dissociation Curve to the right
CO2, acidity, 2,3-BPG, exercise, temperature
118
The deoxy form of hemoglobin has a greater affinity for protons than does oxyhemoglobin
Bohr Effect
119
Stabilizes the T structure of hemoglobin by forming additional salt bridges that must be broken prior to conversion to the R state, synthesized by erythrocytes
2,3-BPG
120
Oxidized form of Hgb (Fe3+) that does not bind to O2 as readily but has a high affinity for CN, cyanosis, anxiety, headache, dyspnea, chocolate cyanosis (muddy brown), 85% O2 Sat.
Methemoglobin
121
Hgb bound to carbon monoxide instead of O2, cherry pink
Carboxyhemoglobin
122
Hemoglobin: CO
Carbohyhemoglobin
123
Hemoglobin: CO2
Carbaminohemoglobin
124
Hemoglobin: cherry pink
Carboxyhemoglobin
125
Hemoglobin: muddy brown
Methemoglobin
126
Hemoglobin: When blood glucose enters erythrocytes, it glycosylates the
ε-amino group of lysine residues and the amino terminals of hemoglobin (HbA1c)
127
Disorder characterized by an inherited (intrinsic) defect in the RBC membrane that renders erythrocytes spheroidal, less deformable and vulnerable to splenic sequestration and destruction
Hereditary Spherocytosis
128
Hereditary Spherocytosis: Mutations
spectrin, band 4.1, band 3
129
Hereditary Spherocytosis: Diagnosis
osmotic fragility test
130
Hereditary Spherocytosis: Treatment
splenectomy for symptomatic patients
131
Point mutation in both genes coding for β-chain that results in a valine rather than a glutamate, homozygous recessive disorder
Sickle Cell Disease
132
Polymerization and decreased solubility of the deoxy form of Hgb, distortion of the RBC membrane, misshapen, rigid RBCs occlude capillaries
Sickle Cell Disease
133
Amenia, tissue anoxia, painful crises, protective against malaria
Sickle Cell Disease
134
Sickle Cell Disease: Treatment
hydration, analgesics, antibiotics if with infection, transfusions, hydroxyurea
135
Hemoglobin variant that has a single amino acid substitution in the 6th position of the β-chain in which lysine is substituted for glutamate, homzygous patients present with mild hemolytic anemia
Hemoglobin C
136
Inadequate synthesis of the α-chains, leads to anemia due to β-chain accumulation and precipitation, symptoms appear at birth because α-chains are needed for HbF and HbA
Alpha Thalassemia
137
Alpha Thalassemia: 1 defective gene
silent carrier
138
Alpha Thalassemia: 2 defective genes
Alpha Thalassemia Trait
139
Alpha Thalassemia: 3 defective genes
Hb H DIsease
140
Alpha Thalassemia: 4 defective genes
Hydrops Fetalis
141
Alpha Thalassemia: Chromosome
Chrom. 16
142
Inadequate synthesis of β-chains, leads to anemia, accumulation of Hb Barts, α-chain precipitation, symptoms appear after birth sins Hbf does not have β-chains
Beta Thalassemia
143
Beta Thalassemia: 1 defective gene
Beta Thalassemia Minor
144
Beta Thalassemia: 2 defective gene
Beta Thalassemia Major
145
MOst abundant protein in the body, long stiff extracellular structure in which 3 polypeptides (α-chain) each 1000 AA in length are wound around one another in a triple helix, stabilized by hydrogen bonds, 28 distinct types made up of 30 distinct polypeptide chains
Collagen
146
Most Common Collagen Type
Type 1
147
Collagen is rich in
Glycine, Proline
148
X portion of collagen
Proline (facilitates kinking)
149
Y portion of collagen
hydroxyproline or hydroxylisine
150
Formed in fibroblasts or in the osteoblasts of bone and chondroblasts of cartilage, secreted into the extracellular matrix
Collagen
151
Collagen monomers aggregate and become cross-linked to form
Collagen Fibrils
152
Collagen: pro α-chain + signal peptide
PrePro α-chain
153
Collagen: signal peptide removed
Pro α-chain
154
Collagen: lysine and proline are hydroxylated
Procollagen
155
Collagen: 3 procollagen chains form the triple helix
Triple Helix Procollagen
156
Collagen: secreted from the cell
Triple Helix
157
Collagen: triple helix with propeptide removed
Tropocollagen
158
Collagen: lysine cross-links, parallel, staggered
Collagen Fibrils
159
Collagen: bone
I
160
Collagen: skin
I
161
Collagen: tendon
I
162
Collagen: dentin
I
163
Collagen: fascia
I
164
Collagen: cornea
I
165
Collagen: late wound repair
I
166
Collagen: cartilage
II
167
Collagen: vitreous body
II
168
Collagen: nucleus pulposus
II
169
Collagen: skin
III
170
Collagen: blood vessels
III
171
Collagen: uterus
III
172
Collagen: fetal tissue
III
173
Collagen: granulation tissue
III
174
Collagen: basement membrane/basal lamina
IV
175
Results from inheritable defects in the metabolism of fibrillar collagen, collagen is most frequently affected
Ehlers-Danlos Syndrome
176
Hyperextensible skin, tendency to bleed, hypermobile joints, high risk for berry aneurysms
Ehlers-Danlos Syndrome
177
Brittle bone syndrome, mutation in collagen genes result to bones that easily bend and fracture, most common form is autosomal dominant with abnormal collagen type
Osteogenesis Imperfecta
178
Multiple fractures, blue sclerae, hearing loss, dental imperfections
Osteogenesis Imperfecta
179
Hydroxylation of collagen is a post-translational modification requirin ascorbic acid. deficiency causes decreased cross-linking of collagen fibers
Scurvy
180
Sore spongy gums, loose teeth, poor wound healing, petechiae on skin and mucous membranes
Scurvy
181
A number of genetic disorders affecting the structure of type IV collagen fibers, the major collagen found in the basement membranes of the renal glomeruli, hematuria, ESRD
Alport's Syndrome
182
Kinky hair, growth retardation, reflects a dietary deficiency of the copper required by lysyl oxidase which catalyzes a key step in formation of the covalent cross-links that strengthen collagen fibers
Menke's Syndrome
183
The skin breaks and blisters as a result of minor trauma, the dystrophic form is due to mutations affecting the structure of type VII collagen which forms delicate fibrils that anchor the basal lamina to collagen fibrils in the dermis
Epidermolysis Bullosa Dystrophica
184
Connective tissue protein with rubber-like properties, responsible for extensibility and elastic recoil in tissues
Elastin
185
Rich in proline and lysine but little hydroxyproline and no hydroxylysine
Elastin
186
Precursor tropoelastin is deposited into an irregular fibrillin scaffold cross-linked by desmosine
Elastin
187
Elastin is found in tissues where elastic recoil is needed like in
lungs, large arteries, elastic ligaments, vocal cords, ligamentum flavum
188
Autosomal dominant connective tissue disorder, mutation in fibrillin gene
Marfan Syndrome
189
Taller, thinner, dolichostenomelia, arachnodactyly, ascending aortic dilatation and dissection
Marfan Syndrome
190
Deficiency in the enzyme that inhibits proteolytic enzymes from hydrolyzing and destroying proteins, elastase destroys the alveolar walls resulting in emphysema
α1 Trypsin Deficiency
191
Many different genetic types, triple helix, (Gly-X-Y)n repeating structure, presence of hydroxylysine, carbohydrate containing, intramolecular aldol cross-links, presence of extension peptides during biosynthesis
Collagen
192
One genetic type, Intramolecular desmosine cross-links
Elastin
193
Net accumulation of proteins as in growth & pregnancy
Positive Nitrogen Balance
194
Net breakdown of protein as in surgery, advanced cancer, kwashiorkor or marasmus, starvation
Negative Nitrogen Balance
195
Protein Turnover per day
300-400g/day
196
Energy-dependent protein degradation mechanism
Ubiquitin-Proteasome Mechanism
197
Protein Degradation: Endogenous
Proteasome
198
Protein Degradation: Exogenous
Lysosome
199
Sum of all free AAs in cells and ECF, degradation and turnover of body protein, dietary intake, synthesis of non-essential AAs
Amino Acid Pool
200
Resorption of Proteins per day
150g/day
201
Degradation of Proteins per day
50-100g/day
202
Protein Digestion: Stomach
HCl, Pepsin
203
Protein Digestion: Pancreatic Enzymes
Zymogens activated by Trypsin
204
Protein Digestion: liberate AAs and dipeptides
Aminopeptidases
205
Protein Digestion: absorbed by secondary active transport
Free AAs
206
Protein Digestion: Endopeptidases
Trypsin, Chymotrypsin, Elastase
207
Protein Digestion: Exopeptidases
Carboxypeptidase, Aminopeptidase
208
HCl is produced by
parietal cells
209
Pepsinogen is produced by
chief cells
210
AA Catabolism: removal of the α-amino group (deamination) forming ammonia and a corresponding α-ketoacid
First Phase
211
AA Catabolism: carbon skeletons of α-ketoacids are converted to common intermediates of energy-producing metabolic pathways (Glycolysis, Krebs Cycle)
Second Phase
212
Major disposal form of nitrogen
Urea
213
Nitrogen Excretion: seen in telostean fish, excrete highly toxic ammonia
Ammonotelic
214
Nitrogen Excretion: land animals, humans, non-toxic water-soluble urea
Ureotelic
215
Nitrogen Excretion: birds, secrete uric acid as semisolid guano
Uricotelic
216
Main steps in removing nitrogen from AA
transamination, oxidative deamination
217
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
218
Aminotransferases
Alanine Aminotransferase (ALT), Aspartate Aminotransferas (AST)
219
Aminotransferases: Co-Enzyme
Pyridoxal Phosphate (B6)
220
ALT is also known as
SGPT (serum glutamate:pyruvate transferase)
221
ALT/SGPT transaminates
pyruvate, alanine
222
AST is also known as
SGOT (serum glutamate:OAA transferase)
223
AST/SGOT transaminates
aspartate, OAA
224
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
225
Oxidative Deamination: Enzyme
Glutamate Dehydrogenase
226
Peripheral Nitrogen Removal: synthesized from glutamate and ammonia, occurs in most tissues, including muscle
Glutamine
227
Peripheral Nitrogen Removal: excess nitrogen from the peripheral tissues can reach the liver through transamination of pyruvate, occurs in muscle
Alanina
228
In the liver, alanine is converted back to pyruvate which may undergo gluconeogenesis which can be transported back to the muscles
Glucose, Alanine Cycle
229
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
230
Krebs-Henseleit Cycle/Ornithine Cycle
Urea Cycle
231
Pathway for removal of nitrogenous waste products in the body, present only in the liver, major disposal of amino groups
Urea Cycle
232
Donors of the atoms of urea
NH3 from free ammonia and aspartate, C from CO2
233
Urea Cycle: only _____ can penetrate the mitochondrial membrane
Citrulline
234
Urea Cycle
Ornithine + Carbamoyl Phosphate → Citrulline + Aspartate → Argininosuccinate - Fumarate → Arginine → Urea + Ornithine
235
Urea Cycle: Mitochondrial Reactions
Formation of Carbamoyl Phosphate and Citrulline
236
Urea Cycle: Cytoplasmic Reactions
Synthesis of Arginosuccinate, Cleavage of Arginosuccinate to form Arginine, Arginine cleavage into Urea and Ornithine
237
Urea Cycle Enzymes: Formation of Carbamoyl Phosphate
Carbamoyl Phosphate Synthetase I
238
Urea Cycle Enzymes: Formation of Citrulline
Ornithine Transcarbamoylase
239
Urea Cycle Enzymes: Synthesis of Arginosuccinate
Arginosuccinate Synthetase
240
Urea Cycle Enzymes: Cleavage of Arginosuccinate to form Arginine
Argininosuccinase
241
Urea Cycle Enzymes: Arginine cleavage into Urea and Ornithine
Arginase
242
Urea Cycle: Substrates
NH3, Aspartate, CO2
243
Urea Cycle: Rate-Limiting Step
CO2 + NH3 → Carbamoyl Phosphate
244
Urea Cycle: Rate-Limiting Enzyme
Carbamoyl Phosphate Synthetase I
245
Urea Cycle: Energy Requirement
4 ATP
246
Urea Cycle: Co-Factors
N-acetylglutamate, Biotin
247
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
248
Enzyme defect in the urea cycle, hyperammonemia, elevated blood glutamine, decreased BUN, lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, death
Hereditary Hyperammonemia
249
Hereditary Hyperammonemia: Type 1 Defect
Carbamoyl Phosphate Synthetase I Deficiency
250
Hereditary Hyperammonemia: Type 2 Defect
Ornithine Transcarbamoylase Deficiency
251
Hereditary Hyperammonemia: Treatment
low protein diet, administration of Na benzoate or phenylpyruvate to capture and excrete excess nitrogen
252
Compromised liver function, tremors, slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision
Acquired Hyperammonemia
253
Exclusively ketogenic AAs
Leucine, Lysine
254
Ketogenic and Glucogenic AAs
Phenylalanine, Tyrosine, Tryptophan, Isoleucine
255
Ketogenic AAs yield
acetoacetate, acetyl-CoA/acetoacetyl-CoA
256
Glucogenic AAs yield
Pyruvate, intermediates of the Krebs Cycle
257
AAs that enter the Krebs Cycle via α-ketoglutarate
Glutamine, Glutamate, Proline, Arginine, Histidine
258
AAs that enter the Krebs Cycle via Pyruvate
Alanine, Serine, Glycine, Cysteine, Threonine, Tryptophan
259
AAs that enter the Krebs Cycle via Fumarate
Phenylalanine, Tyrosine
260
AAs that enter the Krebs Cycle via Succinyl-CoA
Methionine, Valine, Isoleucine, Threonine
261
AAs that enter the Krebs Cycle via Oxaloacetate
Aspartate, Asparagine
262
AAs synthesized from transamination of α-ketoacids
Alanine, Aspartate, Glutamate
263
AAs synthesized from amidation of Glutamate and Aspartate
Glutamine, Asparagine
264
AA synthesized from Glutamate
Proline
265
AA synthesized from Methionine and Serine
Cysteine
266
AA synthesized from 3-phosphoglycerate
Serine
267
AA synthesized from Serine
Glycine
268
AA synthesized from Phenylalanine
Tyrosine
269
AA synthesized into heme, purines, creatine, conjugated to bile acids
Glycine
270
AA synthesized into phospholipid, sphingolipid, purines, thymine
Serine
271
AA synthesized into GABA
Glutamate
272
AA synthesized into thioethanolamine of CoA, taurine
Cysteine
273
AA synthesized into histamine
Histidine
274
AA synthesized into creatinine, polyamines, NO
Arginine
275
AA synthesized into serotonin, NAD, NADP, melatonin
Tryptophan
276
AA synthesized into catecholamine, thyroid hormones (T3 & T4), melanin
Tyrosine
277
Deficiency in phenylalanine hydroxylase or tetrahydrobiopterine cofactor, tyrosine becomes essential, phenylalanine builds up, excess phenylketones (phenylacetate, phenyllactate, phenylpyruvate)
Phenylketonuria
278
Mental retardation, growth retardation, fair skin, eczema, musty body odor
Phenylketonuria
279
Phenylketonuria: Treatment
decrease phynylalanine and increase tyrosine in diet
280
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
281
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
282
Albinism: inability to synthesize melanin from tyrosine, autosomal recessive
Tyrosinase Deficiency
283
Albinism: decreased amounts of tyrosine and thus melanin
Defective Tyrosine Transporters
284
Autosomal recessive, cystathionine synthase deficiency, decreased affinity of cystathione synthase for pyridoxal phosphate, homocysteine methyltransferase deficiency, excess homocysteine, cysteine becomes essential
Homocystinuria
285
Treatment for cystathionine synthase deficiency
decrease methionine, increase cysteine, B6 and folate in the diet
286
Treatment for decreased affinity of cystathione synthase for pyridoxal phosphate
increase B6 in the diet
287
Mental retardation, osteoporosis, tall, kyphosis, lens subluxation (downward, inward), atherosclerosis, stroke, MI
Homocystinuria
288
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
289
Cystinuria: Treatment
Acetazolamide (alkalinize the urine)
290
Kidney Stones in Acidic Urine
uric acid, cystine
291
Kidney Stones in Alkaline Urine
magnesium alkaline phosphate (struvite) from urease producing bacteria (Proteus)
292
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
293
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
294
The heme of hemoglobin contains
iron
295
The heme of chlorophyll contains
magnesium
296
Heme synthesis is present in
all tissues
297
Used in hemoglobin, myoglobin, cytochromes, catalase, peroxidase, guanylate cyclase
heme
298
The initial and the last three steps in the formation of porphyrins occur in
mitochondria
299
The intermediate steps occur in the
cytosol
300
Steps in Heme Synthesis
Formation of δ-aminolevulinic acid, porphobilinogen, uroporphobilinogen, heme
301
Heme Synthesis: Rate-Limiting Step
Glycine + Succinyl CoA → δ-Aminolevulinic Acid
302
Heme Synthesis: Rate-Limiting Enzyme
ALA Synthase
303
Heme Synthesis: ALA Synthase Co-Factor
Pyridoxine (B6)
304
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
305
Introduction of iron (Fe3+) into protoporphyrin IX occurs spontaneously but the rate is enhanced by ferrochelatase, also inhibited by lead
Formation of Heme
306
Genetic or acquired disorders due to abnormalities in the pathway of biosynthesis of heme, erythropoietic or hepatic
Porphyrias
307
Most Common Porphyria
Porphyria Cutanea Tarda
308
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
309
Pyridoxine deficiency associated with Isoniazid therapy
Sideroblastic Anemia (ringed sideroblasts)
310
Heme synthase (ferrochelatase) introduces the Fe2+ into protoporphyrin IX to make the heme ring, microcytic, hypochromic anemia
Iron Deficiency
311
Inactivates many enzymes in heme synthesis (ALA dehydratase, ferrochelatase)
Lead Poisoning
312
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
313
Causes microcytic, hypochromic anemia
IDA, Thalassemia, Lead Poisoning
314
Causes megaloblastic anemia
Folate/B12 Deficiency, Pernicious Anemia
315
Causes normocytic, normochromic anemia
blood loss, chronic disease, CKD
316
Causes increased MCHC
Hereditary Spherocytosis
317
ALA synthase deficiency, anemia, decreased red cell counts and Hgb
X-linked Sideroblastic Anemia
318
Abdominal pain, neuropsychiatric, urinary δ-aminolevulinic acid
ALA Dehydratase Deficiency
319
Uroporphyrinogen I synthase deficiency, abdominal pain, neuropsychiatric, urinary porphobilinogen (+), uroporphyrin (+)
Acute Intermittent Porphyria
320
Uroporphyrinogen III synthase deficiency, no photosensitivity, urinary porphobilinogen (-), uroporphyrin (+)
Congenital Erythropoietic Porphyria
321
Uroporphyrinogen decarboxylase deficiency, photosensitivity, urinary porphobilinogen (-), uroporphyrin (+)
Porphyria Cutanea Tarda
322
Coproporphyrinogen oxidase deficiency, photosensitivity, abdominal pain, neuropsychiatric, urinary porphobilinogen (+), uroporphyrin (+), fecal protoporphyrin (+)
Hereditary Coproporphyria
323
Protoporphyrinogen oxidase deficiency, photosensitivity, abdominal pain, neuropsychiatric, urinary porphobilinogen (+), fecal protoporphyrin (+)
Variegate Porphyria
324
Ferrochelatase deficiency, photosensitivity, fecal protoporphyrin (+), red cell protoporphyrin (+)
Protoporphyria
325
After 120 days, RBCs are taken up and degraded by the
reticuloendothelial system (liver, spleen)
326
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
327
Reactions of heme oxygenase in reticuloendothelial cells
heme → biliverdin (green) → bilirubin (red orange)
328
Bilirubin transported to the liver by binding to
albumin
329
In the liver, bilirubin binds to intracellular proteins particularly
ligandin
330
Bilirubin is conjugated to two molecules of glucuronic acid by
Bilirubin Glucuronyltransferase
331
Bilirubin Glucuronyltransferase Deficiency
Crigler-Najjar I and II, Gilbert Syndrome
332
Transported into the bile canaliculi and then into the bile, susceptible to impairment in liver disease
Bilirubin Diglucuronide
333
In the gut, bilirubin is converted into a colorless substance
urobilinogen
334
Intestinal bacteria oxidize urobilinogen into
stercobilin (brown)
335
Some urobilinogen is reabsorbed from the blood and enters the
portal circulation
336
Remaining urobilinogen is transported by the blood to the kidney where it is converted to
urobilin (yellow)
337
Jaundice: hemolytic anemias, neonatal physiologic jaundice, Crigler-Najjar I and II, Gilbert syndrome, toxic hyperbilirubinemia
Unconjugated Hyperbilirubinemia
338
Jaundice: biliary tree obstruction, Dubin-Johnson syndrome, Rotor Syndrome
Conjugated Hyperbilirubinemia
339
Used to measure total and direct bilirubin
Van den Bergh Reaction
