Proteins Flashcards
1
Q
How do amino acids/ proteins assist with homeostasis?
A
they have pH and osmotic affects that assist with homeostasis
2
Q
structural proteins
A
form scaffolds of the extracellular matrix and of chromatin
3
Q
Membrane Proteins
A
play critical roles in cell signaling
4
Q
Protein Enzymes
A
foundation of anabolic and catabolic metabolism
5
Q
Aberrant Proteins
A
are at the heart of multiple diseases
6
Q
enzyme vs protein malfunction
A
enzyme malfunction = inborn or acquired errors of metabolism
protein malfunction = neurodegenerative conditions and cognitive decline
7
Q
Name the monomer + examples of:
– proteins
– carbohydrates
– lipids
– nucleic acids
A
8
Q
amino acids basic structure
A
central alpha carbon
carboxylate
amino group
hydrogen
side chain R
9
Q
Henderson-Hasselbach equation
A
pH = pKa + log[conjugate base/ conjugate acid]
10
Q
pI of a protein depends on
A
the distribution of R groups
– this is because amide bonds between NH3 and COOH groups eliminate their ability to ionize
11
Q
PI Equation
A
pI = [pKa (COOH) + pKa (NH3)]/2
– this is for a non-ionizable group R
– about 5.5 for a non-ionizable group R
12
Q
buffering capacity of amino acids and proteins
A
+/- 1
13
Q
protein charge based on pH and PI
A
pH > pI = protein charge negative
pH < pI = protein charge positive
14
Q
CO2/ Bicarbonate balance
A
blood pH is determined by the henderson-hasselbach equation and CO2/ bicarbonate play an important role in buffering capacity
– dissolved CO2 = conjugate acid & dissolved HCO3 = conjugate base
15
Q
Electrophoresis
A
done at a pH of 8.6
major plasma proteins separated based on charge differences → migrate towards anode
alterations in normal electrophoretic pattern = stress, trauma, infection, or autoimmune disorder
16
Q
acidosis and alkylosis
A
blood levels of CO2 and bicarbonate = critical factors in maintaining normal blood pH (normal = 7.4)
acidosis and alkylosis = serious complications of metabolic or respiratory imbalance → can cause decrease or increase in blood bicarbonate
17
Q
ionization of drugs affect
A
it’s oral ability, ability to cross placenta/ blood, and ability to cross the blood brain barrier
drug in a unionized (neutral state) is membrane permeable, but a charged drug is not
18
Q
neutral form of weak acidic/ basic drug
A
neutral form of weak acidic drug = conjugate acid
neutral form of weak basic drug = conjugate base
19
Q
what is critical for protein folding
A
the side chains R of amino acids that form a protein
20
Q
hydrophobic vs hydrophilic protein formation
A
hydrophobic proteins = interior of globular proteins while hydrophilic proteins = exterior because they can form intramolecular hydrogen bonds and have interactions with water molecules
21
Q
R groups determine what for an enzyme
A
dictates the specificity of enzyme active sites for the substrate
ex: cysteine = disulfide bonds and proline = break up helix
22
Q
hierarchy of protein formation
A
primary structure - amino acid sequence
secondary structure = polypeptide chain interactions (alpha/Beta sheets)
tertiary structure = side chain interactions
quaternary = higher order structures → association of proteins into multimers or fibrils
23
Q
neurodegenerative diseases occur when
A
a normally globular protein misfolds = exposes hydrophobic residues that cause aggregation and formation of amyloid fibrils or neurofibrillary tangles
24
Q
Alzheimers
A
globular proteins misfolded
AB-42 peptide
25
Frontotemporal dementias
globular protein misfold
tau protein
26
transmissible spongiform encephalopathies
globular protein misfold
– prion protein (PrP)
normal functioning PrP = alpha helix; an increase in B-sheet content occurs because of either a mutation in PrP = less stable alpha helix or because of propagation through an infectious B-sheet rich Prp (**prion**)
27
reasons for an increase in beta sheets in transmissible spongiform encephalopathies
1. mutation in PrP creating a less stable alpha helix
2. self propagation through an infectious Beta-sheet rich PrP → known as a prion
28
stabilization of B-sheets in prion
interlocking hydrogen bonds help stabilization the propagation of B-sheet structure
prions = oligomers
29
misfolded proteins depending on they type
1. amyloid plaques
2. neurobirillary tangles
3. intraceullalar inclusions (Lewy or pick bodies)
30
triple helix in collagen distorted by
mutations in glycine →leads to osteogenesis imprefecta
– need glycine for most defining feature of collagen, which is the triple helix
normal sequence: Gly-Pro-Pro/HyP
31
(severe) anemia genomic cause
a single glutamate to valine mutation at position 6 on the Beta-globin chain renders homoglobin less soluble
32
(mild) sickle cell anemia genomic causes
glutatmate to lysine mutation at position 6
– lysine chain does not affect aggregation (like Valine does)
33
cystic fibrosis genomic causse
F508 mutation = mutant of cystic fibrosis transmembrane receptor
CFTR is misfolded and directed towards proteosomes instead of the cell membrane = cyststic fibrosis
– many examples of specific point mutations + examples of heterogenous mutations in protein sequences that give rise to the disease
34
allostery
small molecule modulators binding to one subunit of a multimer = can trigger a conformational change in other subunits
35
taut vs relaxed
allosteric proteins and enzymes can adopt a relaxed form = high affinity for substrate
taut form = low affinity for substrate
36
hemoglobin
a2B2
– four highly helical subunits and 4 heme groups
– binding of one O2 molecule induces a structural change in neighboring subunits that increases their oxygen affinity
– leads to a sigmoidal O2 binding curve
37
allosteric affectors of hemoglobin
CO2, H+, 2-3-BPG allosteric effectors that stabilize the taut (low) affinity conformer = causes oxygen release
CO binding to the O2 binding site stabilizes the relaxed conformation = prevents oxygen release
38
heterotropic vs homotropic effectors
heterotropic: bind at a different site from substrate
ex: CO2, H+, and 2,3 BPG bind a different site than O2 in hemoglobin
homotropic: bind at the same site as the substrate
ex: CO binds at the same site as O2 in hemoglobin
39
model of hemoglobin binding
hemoglobin is allosterically affected = higher affinity with more oxygen binding
relaxed form = when CO2, H+ or 2,3-BPG bind → leads to release of oxygen
40
sigmoidal O2 curve - hemoglobin
binding of one O2 molecule = structural change in neighboring subunits and increases their oxygen affinity
41
Bohr equations for hemoglobin
HbO2 + H2 ←→ HbH O2
HbO2 + 2,3-BPG ←→ Hb-2,3-BPG + O2
Hb-NH2 + CO2 ←→ Hb-NH-COO + H+
more acidic = release more O2
more CO2 = release O2 (makes sense as hemoglobin goes through tissue = want to release O2)
42
hypoxia effects on hemoglobin
1. hypoxia will cause increased levels of 2-3-BPG to compensate for oxygen deficiency
43
hyperventilation effect on hemoglobin
hyperventilation causes alkylosis (body not able to get out enough CO2) this raises the pH of the blood
as a result, this will decrease the release of oxygen in the tissues
44
Carbon monoxide effect on hemoglobin
**O2 starvation** due to tight binding of CO at the oxygen binding site and stabilization of the relaxed conformer
45
Hemoglobinopathies
ex: B-thalassemia and sickle cell disease
these are typically autosomal recessive because one good allele = can make enough protein for normal function
46
Collagen
most abundant protein in the human body (45 collagen genes)
fibrous protein
47
types of fibrous proteins
collegen
elastic
fibrillin
alpha-keratin
tropomyosin
48
Type I - Type IV collagen
– component of
49
Collagen abnormalities can cause?
aortic and arterial aneurisms
heart valve malfunction
bone fragility
skin distensibility
poor wound healing
joint problems
dislocation of the lens
50
hallmark of collagen
is a triple helix formed by association of 3 polyproline helices (alpha chains)
51
polyproline helices of collagen
alpha chains; **these give collagen it's tensile strength**
may be homotrimers of same gene product or heterotrimers formed by association of different gene products
(Gly-X-Y)n
(X= Proline, Y= Hydroxyproline)
52
role of glycine in collagen
glycine only has H as it' R group = allows the central core of the helix to be tightly wound
– glycine makes up the central core of the helix
53
Proline and Lysine contribution to collagen
Hydroxylated Proline (Hyp) and Hydroxylated Lysine (Hyl) = hydroxylate version of Pro and Lys
they contribute toward teh triple helix strength through hydrogen bonds on the outside of the polyproline helices
54
prolyl hydroxylsae
proline → hydroxyproline
cofactors: vitamin C & Fe2+
55
lysyl hydroxylase
lysine → hydroxylysine
cofactors: vitamin C & Fe2+
56
lysyl oxidase
collagen microbrils formed by 5 interlaced tripe helices that are stabilized by covalent crosslinks **synthesized by lysyl oxidase**
cofactors: vitamin B6 & Cu2+
57
collagen disorders are \_\_\_
autosomal dominant
due to dominant negative effect
– mutated alpha chains distort the triple helix and higher order structure even if two of three alpha chains are normal
58
2 types of autosomal collagen disorders
1. dominant negative effect
2. null mutation (no collagen produced from that gene)
59
tropocollagen molecules
arranged in sets of five staggered helices
– supported by covalent crosslinking → known as collagen microfibril
60
collagen microfibril
5 staggered helices supported by covalent cross linking
61
collagen fibril
interleaved and interwound collagen microfibrils
collagen fibrils = transversely striated
typically aggregate into collagen fibers = then form bundles and sheaths
62
which type of collagen is the most vs lease heavily glycosylated
type I = least
type IV = most
63
vitamin C deficiency
causes scurvy (lysyl hydroxylase and prolyl hydroxylase of collagen synthesis need vitamin C)
Scurvy = accompanied by bleeding gums and poor wound healing
64
Menkes disease
copper deficiency (lysyl oxidase of collagen synthesis uses this)
manifests as bone and joint deformities
65
what happens with age and collagen
increased cross-linking which reduces elasticity and remodeling
66
Osteogenesis Imperfect
due to mutations in glycine = critical for tight packing of collagen triple helix
accompanied by brittle bones
67
Ehlers- Danlos syndrome
defect in collagen processing enzymes (ex: **N/C procollagen peptidase**)
mutations in the sequence of collagen genes can also cause this condition
classic form = EDS hyperextensible skin and joints
68
N/C procollagen peptidase
cleave of procollagen extensions to form tropcollagen
69
enzymes
influence rate of reaction by lower activation energy barrier
sequester substrates into active site
do not alter substrate/ product equilibrium
catalyze reaction in both directions + are regenerated at the end of the rxn
highly specific for substrate
70
clinical significance of enzymes
important drug targets
drugs can act as competitive inhibitors
71
cofactors
small organic molecules that assist with the chemical reaction catalyzed by the enzyme
72
prosthetic groups
may be covalently bound to enzymes and coenzymes = loosly linked
73
substrate vs coenzymes
substrate only binds to a specific enzyme but a coenzyme can bind multiple enzymes
– many coenzymes derived from water-soluble vitamins
74
Thiamine
coenzyme, typical reaction, clinical consequence of def
75
riboflavin
76
Pridyoxine
77
Nicotinic Acid
78
Pantothenic Acid
79
Folic Acid
80
Biotin
81
Cobalamin
(B12)
82
ascorbic acid
83
apo vs holo form
enzymes that require a cofactor = apo/ holo form
apo = when cofactor not bound
holo = when cofactor bound
84
zymogen
inactive precursor of an enzyme
ex: proteases often stored as zymogens as a way to prevent proteolytic cleave of tissues
85
iosenzymes
enzymes with equivalent enzymatic function but variations in primary structure and different kinetic parameters
86
creatine kinase
2 unit subenzyme with 3 isoforms:
BB (brain)
MB (heart)
MM (heart, skeletal muscle)
87
alcoholics suffer from
maladsorption of water soluble vitamins (especially B1, B6, and folic acid)
88
zymogens and anti-proteases critical for
regulation of proteolytic cascade in blood clotting and digestion
89
myocardial infarction markers
detected by CK and LDH isoenzymes detected by serum electrophoresis
enzymes associated with specific tissues or organs are released into blood plasma following cell death
90
oxidoreductase
utilize NAD or FAD electron pool coenzymes = responsible for oxidation and reduction of substrates
91
transferases
transfer a chemical group
ex: kinases phosphorylate proteins
92
hydrolases
cleave bonds by **addition of water**
ex: proteases which cleave peptide groups or bonds in a substrate
93
lyases
remove water, ammonia, or CO2
94
isomerases
rearrange groups or bonds in a substrate
95
ligases
use the energy from ATP to join two molecules together
ex: synthases
96
Bcr-Abl tyrosine kinase
kinases = important in signal transduction
aberrant Bcr-Abl tyrosine kinase = causes chronic myelogenous leukemia and cyclin-dependent Serine and Threonine kinases which regulate cell cycle check points
97
emphysema due to what imbalance
hydrolases in lysosomes break down unwanted cell products = missing or mutated in lysosomal storage disorders
imbalance between proteases and antiproteases in the lungs causes emphysema
98
cirrhosis
oxidoreductase alcohol dehydrogenase (ADH) converts ethanol to acetaldehyde which causes cirrhosis of the liver in high quantities
99
allosteric enzymes
enzymes that demonstrate cooperative substrate binding
rate-determining steps of allosteric enzymes = sensitive to the concentration of substrates and products
100
drugs using allosteric mechanism
finer control over enzyme activity vs competitive inhibitor
101
valium
positive allosteric activator of GABA-A receptor
102
mavaricoc
CCR5 inhibitor of HIV entry
103
enzyme regulation
affected by
1. compartmentalization
2. substrate concentration (M-M kinetics)
3. allosteric regulation
4. transcriptional regulation of enzyme levels (slow)
5. hormonal regulation (signal transduction cascade)
6. covalent regulation (typically phospho/dephosphorylation)
7. activation of proenzymes (typically requires cleavage of N terminal)
104
competitive inhibition
increase of Km
Km = lower enzyme affinity
105
non-competitive inhibition
reduces total amount of enzyme available = **decrease Vmax**
106
uncompetitive inhibition
parallel lines on linear-weaver plot
inhibitor binds to enzyme-substrate complex rather than unoccupied enzyme
107
irreversible inhibition
enzyme completely inactivated = cannot be recovered
108
nerve gas biochemistry rx
irreversible inhibition
organophosphate (nerve gas binds to acteylcholinesterase
109
water-soluble vitamins
typically B vitamins
typically precursors of metabolic pathways
easily excreted in urine (not very toxic in high quantities)
110
fat soluble vitamins
(vitamin A, D, K, E)
absorbed and transported with dietary fat
not readily excreted
build up in liver and adipose tissue and can be toxic in large quantities
111
minerals
classified as electrolytes
large quantities of inorganic ions = dissolved in fluid compartments of the body
112
trace minerals
required for specific enzymes and proteins
113
Vitamin C
UL?, common food sources, consequences of deficiency
114
Vitamin B1
UL?, common food sources, consequences of deficiency
115
Vitamin B2
UL?, common food sources, consequences of deficiency
116
Vitamin B3
UL?, common food sources, consequences of deficiency
117
Vitamin B6
UL?, common food sources, consequences of deficiency
118
Vitamin B9
UL?, common food sources, consequences of deficiency
119
Vitamin B12
UL?, common food sources, consequences of deficiency
120
Biotin
UL?, common food sources, consequences of deficiency
121
Pantothenic acid
UL?, common food sources, consequences of deficiency
122
Choline
123
water soluble vitamins with an upper limit
vitamin C
vitamin b6
vitamin b9
choline
124
vitamin b12 sources only in
animal products
125
high doses of vitamin c result in
diarrhea and gastroinstestinal problems
126
choline - clinical consideration
plays a role in phospholipid structure, neurotransmission (acetylcholine), and methylation
– provides methyl-groups in the form of trimethylglycine (betaine)
127
Vitamin A
UL?, common food sources, consequences of deficiency
128
Vitamin K
UL?, common food sources, consequences of deficiency
129
Vitamin D
UL?, common food sources, consequences of deficiency
130
Vitamin E
UL?, common food sources, consequences of deficiency
131
vitamin A oxides to
retinoic acid = causes transcriptional activation of specific genes via the retinoic acid receptor → binds to DNA
132
retinoic acid leads to gene expression of
keratin and growth and differentiation of epithelial cells
133
retinal and retinol critical for
vision cycle
normal reproduction
(retinoic acid cannot carry out functions of retinol and retinal)
134
y-carboxyglutamate
good chelators of Ca2+
prothrombin-calcium complexes bind to membrane of damaged endothelium and platelets in the initiation of clotting cascade
135
vitamin D group of __ that acts as:
group of sterols that act as hormones by binding to intracellular DNA binding receptors = trigger transcription of genes for regulating plasma levels of Ca2+ and phosphorus
136
excess Vitamin A
dry prurotic skin
enlarged liver
137
all-trans retinoic acid can be used for
topical agent to treat acne and psoriasis
138
12-cis retinoic acid
can be used to treat severe forms of acne
139
Vitamin K made by
gut bacteria
140
dose of vitamin k recommended for
excess causes
recommended for infants (whose gut is sterile)
prolonged administration of vitamin K (menadione) results in damage to RBC's
141
excess vitamin D
deposition of calcium in organs, especially kidneys and arteries
142
excess vitamin E
increase risk of bleeding problems
143
water-soluble vitamins absorbed through
what can affect this?
endothelial cells lining the small and large intestine
– intestinal diseases, resection, or chronic alcohol use can effect their absorption and lead to vitamin deficiencies
144
absorption of fat soluble vitamins
incorporation into mixed micelles with other lipids and bile acids in the lumen of the small intestine and enter enterocytes through diffusion
– pancreatic insufficiency may be accompanied by a deficit of fat soluble vitamins
145
main electrolytes in the body
sodium
potassium
chloride
146
function of main electrolytes in the body
sodium, potassium, chloride
– establish gradients across membranes
– maintain water balance
– neutralize charges on proteins and other biomolecules
147
calcium + phosphorous
structural components of bones and teeth
calcium also involved in hormone action and blood clotting
148
calcium binding/ regulating enzymes include
calmodulin
calbindin
troponin C
calcineurin
149
phosphorus
required for production of ATP
phosphorylation important mechanism of enzyme regulation
important buffer
150
magnesium
activates many enzymes (including all that use ATP as a substrate)
required for DNA polymerase, many DNA repair enzymes, and stabilization of DNA structure
151
sulfur
primary role = amino acid metabolism
ingested in form of cysteine and methionine
152
iron
trace mineral
– most abundant trace metal
– important in O2 transport and redox enzymes
153
zinc
– second most important trace metal
– reacts with insulin
– cofactor in many enzymes
154
copper
essential for processing of connective tissue proteins (collage and elastin) by lysyl oxidase
155
manganese
156
manganese
involved in enzymes of gluconeogensis
plus protein/ fat metabolism
157
iodine
required for synthesis of thyroid hormones
158
molybenum
cofactor in xanthine oxidase
159
selenium
critical in reduction of oxidized glutathione
