50. Protein structure Flashcards
set of all proteins expressed by an individual cell at a particular time
proteome
aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
proteomics
except for this aa, each amino acids has a
•carboxyl group
•amino group
•R group
proline
this amino acid is a major inhibitory neurotransmitter in the spinal cord
glycine
constitutes as a major fraction of free amino acids in the blood
alanine
glycine
Valine
Leucine
Isoleucine
acuumulate in this disease
maple syrup urine disease
precursor of tyrosine
phenylalanine
precursor of homocysteine
methionine
involved in transfer of methyl groups as S-adenosylmethionine (SAM)
methionine
imino acid
proline
contributes to the fibrous structure of collagen
interrupts alpha helices in globular proteins
proline
site of O-linked glycosylation
serine
threonine
tyrosine
precursor of dopamine and epinephrine
tyrosine
precursor of thyroxine and melanin
tyrosine
site for N-linked glycosylation
asparagine
major carrier of nitrogen to the liver from peripheral tissues
glutamine
carrier of ammonia from skeletal muscle to the liver
alanine
precursor of GABA and glutathione
glutamate
precursor of histamine
histidine
used in diagnosis of folic acid deficiency
histidine (FIGIu excretion test)
precursor of creatinine, urea, nitric oxide
arginine
- implicated in neurolathyrism
* progressive and irreversible spastic paralysis of lower extremities
Homourginine,
ß-N-Oxalyldiaminopropionic acid
- neurotoxic amino acid in Cycad seeds
* implicated in ALS-Parkinson dementia complex in natives of Guam
ß-methylaminoalanine
amino acid considered nutritionally semi-essential
arginine
amino acid that can be synthesized the body
cystine
tyrosine
sequencing from N-terminal amino acid
•Sanger’s reagent (1-fluoro-2,4-dinitrobenzene)
Edman’s reagent (Phenylisothiocyanate)
sequencing from C-terminal amino acid
- Hydrazine
* carboxypeptidases
secondary structure of proteins is stabilized by
hydrogen bonding
most common secondary structurte
alpha helix
supersecondary sructures produced by packing side chains from adjacent secondary structural elements close to each other
motifs
overall 3-dimensional shape of the protein
tertiary strucrure
this protein structure is stabilized by disulfide bonds, hydrophobic interactions, hydrogenm bonds and ionic interactions
tertiary structure
fundamental functional and 3 dimensional structural units of polypeptide
domains
number and types of polypeptide units of oligomeric proteins and their spatial arrangement
quaternary structure
results in unfolding and disorganization of the protein’s secondary and tertiary structures
denaturation
rescue proteins
required for proper folding of many species of proteins
chaperones
fatal neurodegenerative diseases characterized by:
•spongiform changes, astrocytic gliomas, neuronal loss
prion diseases
- most common and most important degenerative disease of the brain
- diffuse cerebral atrophy with dementia
- senile plaques and neurofibrillary bundles
- aggregates of protein ß-amyloid
Alzheimer disease
this lipoprotein has been implicated as a potential mediator transformation of soluble alpha helix rich state to beta amyloid that is prone to self-aggregation
apolipoprotein E
configuration of Hemoglobin with low O2 affinity
Taut form (T form)
configuration of Hemoglobin with high O2 affinity
300 X
R form (relaxed)
O2 dissociation curve shows saturation
myoglobin
O2 dissociation curve shows cooperativity
hemoglobin
has allosteric effects
a. myoglobin
b. hemoglobin
b hemoglobin
factors that cause shift to the right of O2 dissociation curve
- ÎÎ CO2
- ÎÎacidity (dec pH)
- ÎÎ 2.3 BPG
- ÎÎ exercise
- ÎÎ Temp
stabilizes the T structure of Hgb by forming additional salt bridges taht must be broken down
prior to conversion to the R state
2,3-BPG
refers to the observation that increases in the carbon dioxide partial pressure of blood or decreases in blood pH result in a lower affinity of hemoglobin for oxygen.
Bohr effect
results from the fact that deoxygenated hemoglobin has a higher affinity (~3.5 x) for CO2 than does oxyhemoglobin. Deoxygenated hemoglobin has a higher affinity for CO2 because it is a better proton acceptor than oxygenated hemoglobin. Therefore, when hemoglobin is deoxygenated (i.e., at tissues) there is a right shift of the carbonic acid-bicarbonate buffer equation to produce H+ which in turn increases the amount of CO2 which can be carried by the blood back to the lungs to be exhaled. Then, with oxygenation at the lungs CO2 dissociates more readily from hemoglobin.
Haldane effect
ζ2 ε2
Embryonal hemoglobin (Hb Gower 1)
α2 γ2
Fetal hemoglobin (HbF)
α2 ß2
Hemoglobin A (HbA)
α2 δ2
Hemoglobin A2
conception up to first few months
Hb Gower 1
First few months to after birth
HbF
8 month onwards
HbA
cutoff of HbA1C to diagnose DM
≥ 6.5%
lowering A1C below ____ has been shown to reduce microvascular and neuropathic complications of DM
7%
for microvascular disease prevention, the A1C goal for nonpregnant adults is
<7%
when blood glucose enters erythrocytes, it glycosylates
- ε- amino group of lysine residues
* amino terminals of Hgb
has 200 x greater affinity for Hgb than O2
CO
Tx for carboxyhemoglobin
100% O2 therapy
oxidized form of Hgb (Fe3+) that does not bind O2, but has higher affinity for cyanide
methemoglobin
s and sx of methemoglobinemia
anxiety
headache
dyspnea
O2 sat: 85%
chocolate cyanosis
methemoglobinemia
tx for methemoglobinemia
Mild: oral methylene blue
or ascorbic acid
•Acute massive due to ingesiton: IV methylene blue
disorder characterized by inherited defect in RBC membrane that renders the erythrocytes speroidal, less deformable and vulnerable to splenic sequestration and detruction
hereditary spherocytosis
mutations associated with hereditary spherocytosis
- ankyrin (most common)
- spectrin
- band 4.1
- band 3
hereditary spherocytosis
manifestations
- anemia
- splenomegaly
- jaundice
lab test for hereditary spherocytosis
osmotic fragility test
inheritance of sickle cell disease
homozygous recessive disorder
results from a point mutation in both genes coding for ß chain that results in a VALINE rather than GLUTAMATE
Sickle cell disease
- polymerization and dec solubility of the deoxy form of Hb
- distortion of the RBC membrane
- Misshapen, rigid RBC occlude capillaries
sickle cell disease
manifestations
Sickle cell disease
anemia
tissue anoxia
painful crises
protective against malaria
tx sickle cell disease
hydration
analgesics
antibiotics if with infection , transfusions, hydroxyurea
Hgb C disease
Hgb variant that has a single amino acid substitution in ____
6th position of the ß-globin chain
•lysine- substituted for glutamate
inadequate synthesis of alpha chains
•symptoms appear at birth
alpha thalassemia
•alpha chains needed for HbF and HbA
leads to anemia, accumulation of Hb Bart (y4) ad Hb H (ß4) and ß chain precipitation
alpha thalassema
inadequate synthesis of beta chains
Beta thalassemia
- symptoms appear after birth
* leads to anemia, accumulation of Hb Barts and alpha chain precipitation
Beta thalassemia
