Proteins Flashcards
Linear polymers of amino acids
Proteins
Set of all proteins expressed by an individual cell at a particular time
Proteome
3 groups that comprise the basic structure of amino acids except proline
Carboxyl group
Amino group
R group (distinctive side chain)
Non polar amino acids
Glycine Alanine Valine Isoleucine Leucine Phenylalanine Tryptophan Methionine Proline
Polar uncharged AAs
-OH
Serine
Threonin
Tyrosine
-SH
Cysteine
Amide
Asparagi e
Glutamine
Charged AAs
Acidic
Aspartate
Glutamate
Basic
Arginine
Lysine
Histidine
Group of AA that have zero net charged
Forms hydrophobic interactions
Found in the interior of protein
Non-polar AA
Group of AAs that have zero net charge
Forms hydrogen bonds
Found in the surface if a protein
Polar uncharged AA
Group of AA that have positive or negative net charge (acidic or basic)
Forms ionic interactions
Found in the surface of a protein
Charged AA
Identify AA
has the smallest side chain
Used in the first step of heme synthesis
Used in synthesis if purines and creatine
Conjugated to bile acids, drugs, and other metabolites
Major inhibitory transmitter in the spinal cord
Glycine
Identify AA
Carrier of ammonia and of carbons of pyruvate from skeletal muscle to liver
Alanine
Identify AA
Together with glycine, contitutes a major fraction if free amino acids in the blood
Alanine
Branched chain amino acids whose metabolites accumulate in MSUD
Valine
Leucine
Isoleucine
Identify AA
Precursor of tyrosine that accumulated in PKU
Phenylalanine
AA with largest side chain
Tryptophan
AA precursor of niacin, serotonin, melatonin
Tryptophan
AA
Source of methyl groups in metabolism
Involve in the transfer if methyl groups as S-adenosylmethionine (SAM)
Methionine
AA
Precursor of homocysteine and cysteine
Methionine
AA
Not an amino acid, but an imino acid
Proline
AA
Contributes to the fibrous structure of collagen and interrupts alpha helices in globular proteins
Proline
Uncharged polar amino acids that contain hydroxyl group
Serine
Threonine
Tyrosine
AA
Site for O-linked glycosylation and phosphorylation of proteins
Serine
Threonine
Tyrosine
AA precursor of thyroxine and melanin
Tyrosine
Fill in
Phenylalanine—>______ —> L Dopa —> _____ —>norepinephrine —-> _____
Tyrosine
Dopamine
Epinephrine
AA
Site for N-linked glycosylation of proteins
Asparagine
AA
When deaminated, it results to formation of ammonia, and is a major carrier of nitrogen to the liver from peripheral tissues
Glutamine
AA
Contains sulfhydryl group that is an active part of many enzymes
Cysteine
AA
Participates in the biosynthesis of coenzyme A
Keratin contains a lot of its derivative
Cysteine
2 AA
Negatively charged at neutral pH due to the carboxylate group
Serve as proton donors
Participate in ionic interactions
Glutamate, Aspartate
AA
Precursor for GABA and glutathione
Glutamate
Name 3 basic AA
Histidine
Arginine
Lysine
At neutral pH,
Arginine and lysine are (+/-) charged
Histidine, being a weak base, has ___ charge
+
Zero
AA
Precursor of histamine
Histidine
AA
Used in the diagnosis of folic acid deficiency (FIGlu excretion test)
Concentration in the brain varies with circadian rhythm
Histidine
Histidine—> (histidinase) —> FIGLU
FIGlu —>______ —> glutamate
Tetrahydrofolate
Folate deficiency elevates urine FIGlu with oral histidine load
AA
precursor of creatine, urea, and NO
Arginine
AA
Precursor of carnitine
Lysine
21st amino acid
Selenocysteine
AA found in a handful of proteins, including certain peroxidases and reductases, where it participates in the catalysis of electron transfer reactions
Selenocysteine
A selenium ion replaces the ____ component of its structural analog, cysteine
Sulfur
AA that is inserted into polypeptide during translation but is not specified by a simple three-letter codon
Selenocysteine
Plant L alpha amino acid
Present in Lathyrus seeds
Implicated in neurolathyrism
Characterized by progressive and irreversible spastic paralysis of the lower extremities
Homoarginine and BETA ODAP
Oxalyldiaminopropionic acid
Neurotoxic amino acid in cycad seeds
Beta methylaminoalanine
AA in cycad seeds impkicated in neurodegenerative diseases, includinf amyotropic lateral sclerosis Parkinson dementia complex in natives if Guam
Beta methylaminoalanin
Except for ____ all AA are chiral
Glycine
All amino acids in proteins are in what configuration
L configuration
Amino acods in bacterial cell walls and antibiotiuvs are in what configuration
D configurarion
Term that denotes an amino acid that bears no net charge at its isoelectric pH (pI)
Zwitterion
Essential amino acids
Phenylalanine Valine Tryptophan Threonine Isoleucine Methionine Histidine Arginine Leucine Lysine
AA that is considered nutritionally semiessential
Arginine
2 AA that can be synthesized in the body, but only from essential amino acid precursors
Cystine
Tyrosine
Stucture of protein determined by a protein’s amino acid sequence
Primary structure
_______ bonds attach the amino group of one amino to the alpha carbonyl group of another
Peptide
Peptide bonds have
Partial (double/single) bond character
(Rigid/non-rigid) and planar
Generally in the (cis/trans) configuration
Disrup by (what process) through prolonged exposure to a strong acid or base
Double bond
Rigid
Trans
Hydrolysis
Stepwise process of identifying the specific amino acid at each position in the peptide chain
Sequencing
2 reagents used for sequencing AA
From N-terminal AA
Sanger’s reagent (1-fluoro-2,4-dinitribenzene)
Edman’s reagent (phenylisothiocyanate)
2 Reagents used for AA sequencing
From c-terminal amino acid
Hydralazine
Carboxypeptidase
Level of protein stucture described as folding of short (3-30 residue) contiguous segments of polypeptide into geometrically ordered units
Secondary structure
Level of protein structure stabilized by Hydrogen bonding
Secondary
Secondary protein structure is stabilized by
Hydrogen bonds
2 forms of secondary stucture
Alpha helix
Beta sheet
More common form of secondary protein structure
Alpha helix
Form of secondary protein structure
Spiral, with polypeptide backbone core, with side chains extending outward
Alpha helix
How many AA per turn in alpha helix protein stucture
3.66
Alpha helix protein structure is disrupted by what
Proline, AAS with large or charged R groups
Keratin and hemoglobin are examples of proteins in what structure
Alpha helix (secondary structure)
Keratin (100% alpha helix)
Hemiglobin (80% alpha helix)
Protein structure wherein AA residues form a zigzagor pleated pattern
Beta sheet
In beta sheet protein stucture, R groups of adjacent residues project in (opposite/same) directions
Opposite
Amyloid and immunoglobulin are examples of proteins in what structure?
Beta sheet (secondary)
These are protein structures with less regukar configuration forming loops and bends
Non- repetitive secondary structures
______ are supersecondary structures produced by packing side chains from adjacent secondary structural elements close to each other
Motifs
Examples are beta-alpha-beta unit
Greek key
Beta meander
Beta barrel
Overall 3-dimensional shape of protein
Includes globular and fibrous proteins
Tertiary structure
The assembly of secondary structural units into larger functional units such as the mature polypeptide and its component domains
Tertiary structure
4 bonds/interactions that stabilize tertiary protein structure
Disulfide bonds
Hydrophobic interactions
Hydrogen bonds
Ionic interactions
Fundamental functional and three dimensional structural units of polypeptide
Domains
Level of protein structure
Number and types of polypeptide units oligomeric proteins and their spatial arrangements
Quaternary structure
Protein stucture that includes
monomeric vs dimeric
Homidimers vs heterodimers
Quaternary stucture
Specialized group of proteins required for the proper folding of many species of proteins
Prevents aggregation, paves the way for the formation of appropriate secondary structural elements and their subsequent coalescence into a molten globule
Chaperones
Specialized group if proteins that can rescue other proteins that have become thermodynamically trapped in a misfolded dead end by unfolding hydrophobic regions
Chaperones
Process that results in the unfolding and disorganization of the proteins secondary and tertiary structures
Denaturation
Protein stuctures destroyed by denaturation
Secondary and tertiary
T/F protein denaturation is accompanied by hydrolysis of peptide bonds
F
T/F protein denaturation may be reversibel, but most proteins remain permanently disordered
T
Fatal neurodegenrative diseases characterized by spongiform changes, astrocytic gliomas, and neuronal loss resulting from the deposition of insoluble protein aggregates in neural cells
Prion Diseases
T/F prion diseases can be transmitted by protein alone, without involvement of DNA or RNA
T
Re Prion Dses:
An altered version of a protein converts normal protein (PrPc, rich in ______) to the pathognomonic conformation (PrPsc, rich in _____)
Alpha helices
Beta sheets
Disease characterized with senile plaques and neurofibrillary tangles that contain aggregates of protein beta amyloid
Alzheimers dse
In Alzheimers dse, B amyloid becomes elevated, and this protein undergoes a conformational change from a soluble alpha helix rich state in beta sheets prone to self-aggregation
Alzheimer
Conformational transformation of protein in alzheimers dse is implicated to_____^
Apolipoprotein E
Examples of globular proteins
Hemoglobin
Myoglobin
Hemoglobin form with low oxygen affinity
Taut form
Hemiglobin form with high oxygen affinity
R (relaxed) form
This principle states that hemoglobin binds up to 4 molecules of oxygen with increasing affinity
Positive cooperativity
Heme protein found exclusively in RBC
Hemoglobin
Heme protein present in heart and skeletal muscle
Myoglobin
Reservoir of oxygen
Oxygen carrier that increase the rate of transport of oxygen within the muscle
Myoglobin
Myoglobin/Hemoglobin
1 polypeptide
Myoglobin
Myoglobin/Hemoglobin
4 polypeptides
Hemoglobin
Myoglobin/Hemoglobin
Binds to 1 oxygen only
Myoglobin
Myoglobin/Hemoglobin
Binds ro 4 oxygen molecules
Hemoglobin
Myoglobin/Hemoglobin
Hyperbolic oxygen dissociation curve
Myoglobin
Myoglobin/Hemoglobin
Oxygen dissociation curve id sigmoidal
Demonstrates cooperativity
Hemoglobin
Myoglobin/Hemoglobin
Oxygen storage
Myoglobin
Myoglobin/Hemoglobin
Oxygen transport
Hemoglobin
Myoglobin/Hemoglobin
Absent allosteric effects
Myoglobin
Myoglobin/Hemoglobin
Present allosteric effects
Hemoglobin
Factors that shift O2-Hgb dissociation curve to the right
CO2 Acidity 2,3 BPG Exercise Temperature
Stabilizes the T structure of hemoglobin by fprming additional salt bridges that must be broken prior to conversion to the R state
2, 3 BPG
T/F
In infants, 2,3 BPG binds more weakly to HbF than to HbA. Hence, HbF has higher affinity to oxygen than HbA
T
T/F
Prolonged exposure to high altitude increases the number of erythrocytes. Hence, increased hemoglobin and increased BPG lowers the affinity of HbA for 02
T
A low pO2 in peripheral tissues (promotes/inhibits) the synthesis in erythrocytes of 2,3 BPG from the glycolytic intermediate 1,3 BPG
Promotes
This effect describes that the release of oxygen from hemoglobin is increased when the pH is lowered or when the hemoglobin is in the presence of increased pCO2
BOHR effect
T/F
Oxyhemoglobin has greater affinity for protons than does deoxy form
F
The effect of changes in hemoglobin saturation on the relationship of CO2 content to PCO2
Haldane effect
Minor type of hemoglobin
Produced from conception to first few months
Embryonal hemoglobin
Hb Gower 1
Hb Gower 1
(Embryonal Hemoglobin) is synthesized where?
Yolk Sac
Identify minor hemoglobin
Alpha2gamma2
Fetal hemoglobin
HbF
Minor Hgb synthesized first few months to after birth
HbF (Fetal Hgb)
Minor Hgb synthesized in the liver
HbF (Fetal Hemoglobin)
Minor hgb with alpha2 beta 2 chains
HbA
Hemoglobin A
Minor hemoglobin synthesized 8 months and onwards
HbA
Minor hemoglobin synthesized in marrow
HbA and HbA2
Minor Hgb
Alpha2 delta 2
HbA2
Minor Hgb synthesized shortly after birth onwards
HbA2
Site if synthesis of HbA2
Marrow
Major Hgb found in fetus
Has increased affinity doe oxygen than HbA
Fetal Hgb
HbF
Hgb with 2 alpha and 2 delta chains
HbA2
Comprises 2% of total adult Hgb
HbA2
HbA1C forms when glucose enters RBC and glycates_____ residues and the amino terminals of Hgb
Epsilon amino group of lysine
Based on ADA recommendations, cutoff of HbA1C for the diagnosis of diabetes is >/=____
6.5 %
Lowering A1C to below ___% has been shown to reduce micrivascular and neuropathic complications of type 1 and type 2 DM
7
Form of Hgb bound to carbon monoxide in place of oxygen
Hb becomes cherry pink in color
Carboxyhemoglobin
CO has ___ times greater afficnitu for Hgb than oxygen
200
Oxidized form of Hgb (Fe3+) that does nor bind oxygen as readily but has increased affinity for cyanide
Methemoglobin
Chocolate cyanosis, O2 saturation is at 85%
Anxiety, headache, dyspnea
Methemoglobinemia
Treatment for methemoglobinemia
Methylene blue or ascorbic acid (both reducing agents)
Treatment for acute massive methemoglobinemia due to ingestion of chemicals
IV methylene blue
Disorder characterized by an inherited defect in the RBC membrane that renders the erythrocytes spheroidal, less deformable , and vulnerable to splenic sequestration
Hereditary spherocytosis
Mutation in what protein is most commonly implicated in hereditary spherocytosis
Ankyrin
Others:
Spectrin
Band 4.1
Band 3
Diagnostic method for hereditary spherocytosis
Osmotic fragility test
Treatment for symptomatic hereditary spherocytosis
Splenectomy
Disease that results from point mutation in both genes coding for the beta chain that results to
Glutamine—>valine
Sickle cell dse
Polymerization and decreased solubility of the deoxy form of Hb
Distortion of the RBC membrane
Misshapen, rigid RBCs that occlude capillaries
Sickle cell dse
Anemia
Splenomegaly
Jaundice
Hereditary spherocytosis
Anemia
Tissue anoxia
Painful crises
Protective against malaria
Sickle cell dse
Treatment for sickle cell dse
Hydration Analgesics Antibiotics if with infection Transfusions Hydroxyurea
Hemoglobin variant that has a single amino acid substitution in 6th position of the beta globin chain, in which glutamate—->lysine
Hemoglobin C
In hemoglobin C disease,
Glutamate —-> _____
Lysine
T/F patients with Hgb C present with severe hemolytic anemia
F
Mild
T/F
No specific therapy is required for Hgb C
T
Inadequate synthesis of alpha chains
Anemia
Acumulation of Hb Bart (gamma 4) and Hb H (beta 4), and Beta chain precipitation
Alpha thalassemia
In alpha thalassemia, symptoms appear at birth
T/F
T
because alpha chains are needed for HbF and HbA
Silent carrier—>_____—>HbH disease —>Hydrops fetalis
Alpha thalassemia trait
Inadequate synthesis of beta chains
Anemia
Accumulation if Hb Barts
And alpha chain precipitation
Beta thalassemia
T/F symptoms of beta thalassemia appear only AFTER birth
T
2 examples of fobrous proteins
Collagen
Elastin
Most abundant protein in the body
Collagen
Collagen structure is stabilized by ____ bonds
Hydrogen
A long stiff extracellular structure in which 3 polypeptides (a chains) each 1000 AA in length are wound around ine another in a triple helix
Collagen
Most common form of collagen
Type I
Collagen is rich in what 2 AA
Proline
Glycine
Facilitates kinking of the collagen structure
Proline
Type of collagen found in BONE, skin, tendond, dentin, fascia, cornea, late wound repair
I
Type of collagen found in CARTILAGE (including hyaline), vitreous body, nucleus pulposus
II
Type of collagen found in RETICULIN, skin, blood vessels, uterus, fetal tissues, granulation tissue
III
Type of collagen found in basemend membrane or basal lamina
Type IV
Type of collagen beneath stratified squamous epithelium
Type 7
Inherited disorder
Hyperextensibility of skin
Abnormal tissue fragility
Increased joint mobility
Ehlers Danlos Syndrome
Subtype of Ehlers Danlos Defect in Type I and Type V collagen Joint hypermobility Severe skin abnormalities Less severe joint changes
Classical
Subtype of Ehlers Danlos Defect in Type III collagen Joint hypermobility Skin abn Sever joint pain Most common subtype
Hypermobility
Ehlers Danlos Subtype
Type III
Fragile blood vessels and organs, small stature, thin and transluscent skin, easy bruising
Increased risk for intracranial aneurysms
Most serious
Vascular
Multiple fractures
Blue sclerae
Hearinf loss
Dental imperfections
Osteogenesis imperfecta
Most common form of osteogenesis imperfecta is autosomal _____ with abnormal collagen type ____
Dominant
Type I
Main presenting sign of Alport syndrome
Hematuria
Hematuria
Ocular lesions
Hearing loss
End stage renal dse
Alport syndrome
Alport syndrome is defect in what type of collagen
IV
Skin breaks and blisters
Defect in type VII collagen, which anchors the basal lamina to collagen fibrils in the dermis
Epidermolysis bullosa
Sore spongy gums
Loose teeth
Poor wound healing
Petechiae on skin and mucous membrane
Scurvy
Deficiency of this vitamin causes decreased cross linking of collagen fibers
Vitamin C
Hydroxylation of collagen is a post-transcriptional modification requiring _______
Ascorbic acid
Kinky hair and growth retardation
Dietary deficiency of copper required by lysyl oxidase
Menke’s disease
Menkes dse reflects a dietary deficiency of copper required by _____
Lysyl oxidase
Tissues that contain elastin
Lungs Large arteries Elastic ligaments Vocal cords Ligamentum flavum
______, precursor of elastin, is deposited into irregular fibrillin scaffold cross-linked by _____
Tropoelastin
Desmosine
Marfan syndrome is caused by mutation by ______ gene
Fibrillin
Taller and thinner than family members Dolichostenomelia Arachnodactyly Aortic dilatation and dissection Upward dislocation of lens (ectopia lentis)
Marfan syndrome
Airtic dilatation occurs in __ % of patients with Marfan syndrome
70-80
Deficiency inhibits proteolytic enzymes from hydrolyzing and destroying proteins
Alpha 1 antitrypsin
Liver disease (cirrhosis and HCC) Emphysema (due to alveolar wall destruction by elastase)
Alpha 1 antitrypsin deficiency
