PROTEINS Flashcards
Contains an INDOLE RING
Tryptophan (W)
- The skin breaks and blisters as a result of minor trauma
- Dystrophic form is due to mutations affecting the structure of type VII collagen, which anchors the basal lamina to collagen fibrils in the dermis
EPIDERMOLYSIS BULLOSA
Contains Guanidino Group
Arginine (R)
- Disorder characterized by an inherited (intrinsic) defect in the RBC membrane that renders the erythrocytes spheroidal, less deformable, and vulnerable to splenic sequestration and destruction
- Multiple mutations have been described: ankyrin (most common), spectrin, band 4.1 and band 3
HEREDITARY SPHEROCYTOSIS
- Hemoglobin variant that has a single amino acid substitution in the 6 th position of the β-globin chain, in which lysine is substituted for glutamate
- Patients homozygous for hemoglobin C present with mild hemolytic anemia
HEMOGLOBIN C DISEASE
- Partial double-bond character
- Rigid and planar
- Generally in the trans configuration
- Disrupted by hydrolysis through prolonged exposure to a strong acid or base at elevated temperatures
Peptide Bonds
• 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 I
OSTEOGENESIS IMPERFECTA
- Multiple fractures (need to rule out child abuse)
- Blue sclerae
- Hearing loss
- Dental imperfections
Uncharged POLAR AA
STCY QN
Serine (S), (Threonine (T), Cysteine (C), Tyrosine (Y), Glutamine (Q), Asparagine (N)
secondary structure is stabilized by what bond?
hydrogen bonding
attach the α-amino group of one amino to the α carbonyl group of another
Peptide bonds
z 2 ε 2 Hb
Embryonal hemoglobin (Hb Gower 1)
refers to carbon monoxide bound to hemoglobin
carbohyxhemoglobin
- Present in Lathyrus seeds
- Implicated in neurolathyrism, characterized by progressive and irreversible spastic paralysis of the lower extremities
Homoarginine and β-N-Oxalyldiaminopriopionic acid (β-ODAP)
Basic AA
- Proton acceptors
“BASIC HKR”
Histidine (H)
Lysine (K)
Arginine (R)
- At neutral pH:
- Arginine and lysine are positively charged
- Histidine, being a weak base, has no charge
• Genetic disorders affecting the structure of type IV collagen fibers, the major collagen found in the basement membranes of the renal glomeruli
ALPORT SYNDROME
- Hematuria (main presenting sign)
- Ocular lesions
- Hearing loss
- Patients may eventually develop end-stage renal disease
Collagen is rich in what AAs?
glycine and proline
Precursor of carnitine
LYSINE
NON POLAR AA
“GAVIL Pro MidWiFe”
- Glycine (G)
- Alanine (A)
- Valine (V)
- Isoleucine (I)
- Leucine (L)
- Proline (P)
- Methionine (M)
- Tryptophan (W)
- Phenylalanine (F)
- Autosomal dominant connective tissue disorder
- Mutation in the fibrillin gene
MARFAN SYNDROME
- Usually taller and thinner than family members
- Dolichostenomelia
- Arachnodactyly
- Aortic dilatation (70 to 80%) and dissection
- Upward dislocation of the lens (ectopia lentis)
Heme protein present in heart and skeletal muscle
MYOGLOBIN
- Not an amino, but an imino acid
- Contributes to the fibrous structure of collagen and interrupts αhelices in globular proteins
PROLINE
Types of Collagen
- Most common type of secondary structure
- Spiral structure with polypeptide backbone core, with side chains extending outward
- 3.6 AA per turn
- Disrupted by proline, AAs with large or charged R-groups
Alpha Helix
• Examples:
o Keratin (100% α-helix)
o Hemoglobin (80% α-helix)
PHENYLALANINE / TYROSINE DERIVATIVES
Pare, True Love Does Not Exist To Me
Phenylalanine →Tyrosine → L-dopa → Dopamine → Norepinephrine → Epinephrine
Tyroxine, Melanin
R (relaxed) form: ____ oxygen affinity (300x)
high
The set of all the proteins expressed by an individual cell at a particular time
PROTEOME
*Unlike your genome which remains the same throughout life, your proteome changes all the time.
contains IMIDAZOLE RING
Histidine (H)
- Connective tissue protein with rubber-like properties, responsible for extensibility and elastic recoil in tissues
- Found in tissues where elastic recoil is needed
- lungs, large arteries, elastic ligaments, vocal cords, ligamentum flavum
- Rich in proline and lysine, but contains little hydroxyproline and no hydroxylysine
- Precursor tropoelastin is deposited into an irregular fibrillin scaffold cross-linked by desmosine
ELASTIN
- Source of methyl groups in metabolism
- Involved in transfer of methyl groups as S-adenosylmethionine (SAM)
- Precursor of homocysteine and cysteine
METHIONINE
- Precursor of histamine
- Also used in the diagnosis of folic acid deficiency (FIGLU excretion test)
- Concentration in the brain hypothalamus varies in accordance with the circadian rhythm
Histidine
Contains a BENZENE RING
Phenylalanine (F)
α 2 β 2 Hb
Hemoglobin A (HbA)
21st AMINO ACID
SELENOCYSTEINE
- Found in a handful of proteins, including certain peroxidases and reductases, where it participates in the catalysis of electron transfer reactions
- A selenium atom replaces the sulfur of its structural analog, cysteine
- Inserted into polypeptides during translation but is not specified by a simple three-letter codon
- When blood glucose enters the erythrocytes, it glycates the ε amino group of lysine residues and the amino terminals of hemoglobin
- ↑ glycation of hemoglobin noted in patients with diabetes mellitus due to ↑ glucose in blood
GLYCATED HEMOGLOBIN (HbA1C)
• The folding of short (3–30 residue) contiguous segments of polypeptide into geometrically ordered units
SECONDARY STRUCTURE
- Contains a sulfhydryl group that is an active part of many enzymes
- Participates in the biosynthesis of coenzyme A
- Two cysteines can be connected by a covalent disulfide bond to form cystine
CYSTEINE
- Inadequate synthesis of α-chains
- Leads to anemia, accumulation of Hb Bart (γ4 )and Hb H (β4 ), and β-chain precipitation
- Silent Carrier → α-thalassemia Trait → Hb H Disease → Hydrops Fetalis
- Symptoms appear at birth because α-chains are needed for HbF and HbA
ALPHA THALASSEMIA
• Branched-chain amino acids whose metabolites accumulate in maple syrup urine disease
VALINE, LEUCINE, ISOLEUCINE
- Neurotoxic amino acid in Cycad seeds
- Implicated in neurodegenerative diseases, including amyotropic lateral sclerosis-Parkinson dementia complex in natives of Guam
β-Methylaminoalanine
Myoglobin vs Hemoglobin
Precursor of creatinine, urea and nitric oxide
ARGININE
T (taut) form: ____ oxygen affinity
low
- Accumulates in phenylketonuria
- Precursor of tyrosine
PHENYLALANINE
Acidic AA
- Negatively charged at neutral pH because of the carboxylate group
- Participate in ionic interactions
- Serve as proton donors
Aspartate (D)
Glutamate (E)
- Carrier of ammonia and of the carbons of pyruvate from skeletal muscle to liver
- Together with glycine, constitutes a major fraction of free amino acids in the blood
ALANINE
AA with sulfhydril (-SH)
Cysteine
Except for______, all amino acids are chiral
glycine
- Characterized by kinky hair and growth retardation
- Reflects a dietary deficiency of the copper required by lysyl oxidase
- Catalyzes a key step in formation of the covalent cross-links that strengthen collagen fibers
MENKES DISEASE
- Has the smallest side chain
- Used in the first step of heme synthesis: Glycine + Succinyl CoA to δ-ALA
- Used in synthesis of purines and creatine
- Conjugated to bile acids, drugs, and other metabolites
- Major inhibitory neurotransmitter in the spinal cord
Glycine
Fatal neurodenegerative diseases characterized by spongiform changes, astrocytic gliomas, and neuronal loss resulting from the deposition of insoluble protein aggregates in neural cells
PRION DISEASES
- Inadequate synthesis of β-chains
- Leads to anemia, accumulation of Hb Barts and α-chain precipitation
- β-thalassemia Minor → β-thalassemia Major
BETA THALASSEMIA
- Consists of 2 α-chains and 2 γ-chains
- Major hemoglobin found in the fetus (~60%)
- Normally less than 0.6% in adults
- Has ↑ affinity for O 2 than HbA
FETAL HEMOGLOBIN (HbF)
- Supersecondary structures produced by packing side chains from adjacent secondary structural elements close to each other
- Examples are β-α-β unit, Greek key, β-meander, β-barrel
Motifs
- Hydroxylation of collagen is a post-translational modification requiring ascorbic acid
- Vitamin C deficiency causes ↓ cross-linking of collagen fibers
Scurvy
o Sore spongy gums
o Loose teeth
o Poor wound healing
o Petechiae on skin and mucous membranes
An amino acid bears no net charge (zwitterion) at its ____
isoelectric pH (pI)
Most common type of collagen
Type I
Collagen structure
- Rich in glycine and proline
- X: proline (facilitates kinking)
- Y: hydroxyproline or hydroxylysine
Factors that cause a shift to the RIGHT:
o ↑ CO 2
o ↑ Acidity (↓pH)
o ↑ 2,3 BPG
o ↑ Exercise
o ↑ Temperature
carbon dioxide bound to hemoglobin
carbaminohemoglobin
- Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
- A major goal is the identification of proteins and of their posttranslational modifications whose appearance or disappearance correlates with physiologic phenomena, aging, or specific diseases
PROTEOMICS
- Has the largest side chain
- Precursor for niacin, serotonin, and melatonin
TRYPTOPHAN
• Stepwise process of identifying the specific amino acid at each position in the peptide chain
Sequencing
- The release of oxygen from hemoglobin is enhanced when the pH is lowered or when the hemoglobin is in the presence of an increased pCO2
- Both result in a decreased oxygen affinity of hemoglobin
- The deoxy form of hemoglobin has a greater affinity for protons than does oxyhemoglobin
BOHR EFFECT
EHLERS-DANLOS SYNDROME SUBTYPES
- Group of inherited disorders characterized by:
- Hyperextensibility of the skin
- Abnormal tissue fragility
- Increased joint mobility
precursor for GABA and glutathione
Glutamate
*Recall that GABA is the major inhibitory NT in the brain; Glutamate is excitatory (meron din sa MSG). Glu → GABA is catalyzed by Glu- decarboxylase
α 2 δ 2 Hb
Hemoglobin A2 (HbA2)
- α-1 antitrypsin inhibits proteolytic enzymes from hydrolyzing and destroying proteins
- If there is ↓ α-1 antitrypsin in the lungs, elastase destroys the alveolar walls, resulting to emphysema
- Patients can also manifest with liver disease (eg, cirrhosis and hepatocellular carcinoma)
α-1 ANTITRYPSIN DEFICIENCY
*Imagine elastase as if it were scissors that keep on cutting elastin. α-1 antitrypsin prevents it from doing so.
- Number and types of polypeptide units of oligomeric proteins and their spatial arrangement
- Monomeric vs Dimeric proteins
- Homodimers vs Heterodimers
QUATERNARY STRUCTURE
Fundamental functional and three-dimensional structural units of polypeptide
Domains
Contains an IMINO ACID
Proline (P)
AA with polar Hydroxyl (-OH) group
Threonine (T), Tyrosine (Y), Serine (S)
ESSENTIAL AMINO ACIDS
Amino acids whose intake is essential for proper body function since they cannot be synthesized
PVT TIM HALL, always ARGues, never TYRes. A is always ARGinine. T is never TYRosine.
Phenylalanine
Valine
Threonine
Tryptophan
Isoleucine
Methionine
Histidine
Arginine
Leucine
Lysine
• Have a carbonyl group and an amide group that can also form hydrogen bonds
Asparagine (N), Glutamine (Q)
- Asparagine is the site for N-linked glycosylation of proteins
- Glutamine is deaminated by glutaminase resulting in the formation of ammonia, and is a major carrier of nitrogen to the liver from peripheral tissues
Sequencing from the C-terminal amino acid:
§ Hydrazine
§ Carboxypeptidase
TRYPTOPHAN DERIVATIVES
TRYp Mo Siya, ‘No?
TRYptophan Melatonin Serotonin Niacin
Sequencing from the N-terminal amino acid:
§ Sanger’s reagent (1-fluoro-2,4-dinitrobenzene)
§ Edman’s reagent (Phenylisothiocyanate)
• Specialized 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
• Can also “rescue” proteins that have become thermodynamically trapped in a misfolded dead end by unfolding hydrophobic regions
CHAPERONES
- Results in the unfolding and disorganization of the protein’s secondary and tertiary structures
- Not accompanied by hydrolysis of peptide bonds
- Results from denaturing agents:
o Heat, organic solvents, mechanical mixing, strong acids or bases, detergents, ions of heavy metals (e.g., lead, mercury)
• May be reversible, but most proteins remain permanently disordered
DENATURATION
- Amino acid residues form a zigzag or pleated pattern
- R groups of adjacent residues project in opposite directions
- Sheets can be parallel or antiparallel
Beta Sheet
- Examples:
- Amyloid
- Immunoglobulin
- Results from a missense point mutation in both genes coding for the β chain that results in a valine rather than a glutamate
- Homozygous recessive disorder
SICKLE CELL DISEASE
* Missense point mutation ito. E6V (glutamic E naging Val V sa 6th position sa β-chain). Di ba nonpolar ang Val, polar (-) charged ang Glu. Nonpolar areas can attract one another forming a hydrophobic patch which can bara in some blood vessels resulting to painful crisis. This happens under deoxygenated states (if ↓ Oxygen kasi mas exposed si Val so mas magform ng patch).
- Overall 3-dimensional shape of the protein
- Globular proteins vs Fibrous proteins
- The assembly of secondary structural units into larger functional units such as the mature polypeptide and its component domains
- Stabilized by disulfide bonds, hydrophobic interactions, hydrogen bonds, and ionic interactions
TERTIARY STRUCTURE
- The effect of changes in oxyhemoglobin saturation on the relationship of CO2 content to pCO2
- O2 bound to hemoglobin changes its affinity for CO2 , such that when less O2 is bound, the affinity of hemoglobin for CO2 increases
HALDANE EFFECT
Determined by a protein’s amino acid sequence
PRIMARY STRUCTURE
- Most common and most important degenerative disease of the brain, presenting with diffuse cerebral atrophy with dementia
- The characteristic senile plaques and neurofibrillary bundles contain aggregates of the protein β-amyloid
- β-amyloid becomes elevated, and this protein undergoes a conformational transformation from a soluble α-helix rich state to a state rich in β sheet and prone to self-aggregation
- Apolipoprotein E has been implicated as a potential mediator of this conformational transformation
ALZHEIMER DISEASE
- Most abundant protein in the body
- A long stiff extracellular structure in which 3 polypeptides (αchains) each 1000 AA in length are wound around one another in a triple helix
- Stabilized by hydrogen bonds
- At least 28 distinct types made up of over 30 distinct polypeptide chains have been identified in human tissues
COLLAGEN
