Section II (Chapters 4, 6-9) Flashcards
(208 cards)
1
Q
Why is water a good solvent for electrolytes?
A
Since they are dipolar molecules, they can form hydrogen bonds easier via uneven electrons
2
Q
If molecules hydrogen bond with water molecules, it means…
A
Dissolve readily in water
3
Q
Hydrogen bonds between water & polar solutes
A
Continuously dissociate and reform
4
Q
Water has a high heat of…
A
Fusion, making it a good thermoregulator
5
Q
What is a hydrogen bond?
A
Weak noncovalent interaction between hydrogen of one molecule and more electronegative of acceptor molecule
6
Q
In a polar environment, molecules can … to form network of hydrogen bonds with water
A
dissolve
7
Q
In a nonpolar environment, molecules do…dissolve, which causes them to form
A
Not, hydration shells
8
Q
What is osmolality?
A
Water distributes between compartments according to concentration of solutes (osmolality), moves from component with lower osmolality (lower concentration of solutes) to higher concentration (high osmolality) to achieve balance
9
Q
What occurs in hyperglycemia?
A
Excess glucose or ketones in blood increase blood osmolality, pulling extra water into cells with it, thus when passed through kidney, increased water is excreted in urine, leading to overall dehydration of cells
10
Q
What is pH?
A
Negative log10 of hydrogen concentration expressed in moles per L (pH = -log[H+])
11
Q
What is an acid?
A
Substance that can release hydrogen ions/protons
12
Q
What is a base?
A
Substance that can accept hydrogen ions/protons
13
Q
What is a buffer?
A
Mixture of undossociated acid and its conjugate base (form of the acid that has lost its proton), resists changes in pH when H or OH are added
14
Q
What is the pKa?
A
Negative log of dissociation constant Ka, buffer has greatest buffering capacity when pH is near pKa
15
Q
What does strong acid mean?
A
Dissociates completely within water
16
Q
What is an example of a strong acid?
A
Sulfuric acid
17
Q
What is an example of a weak acid?
A
Lactic acid, citric acid
18
Q
Interpretation of titration curve
A
- Midpoint is when 0.5 equivalents of OH have been added and half of conjugate acid is dissociated = pKa
- Adding OH causes shift to right, H dissociates from acid and combines with OH to form water = minimal change in pH
- Adding H causes shift to left, conjugate base A- combine with H to form HA = minimal change in pH
19
Q
If pH is above pKa…
A
Basic form
20
Q
If pH = pKa
A
Balanced at 50% basic and acidic form (A-/HA = 1)
21
Q
If pH is below pKa
A
Acidic form
22
Q
What is the physiological pH?
A
7.4
23
Q
Added OH causes
A
Dissociation of acid and H to combine in order to form water
24
Q
What is the Henderson-Hasselbach equation?
A
pH = pKa + log ([A-]/[HA])
25
What is the major source of acid?
CO2
26
Where does CO2 diffuse?
Diffuses into interstitial fluid, then blood plasma, then into RBC
27
Where does phosphate buffer occur?
All cells
28
Where does protein buffer occur?
Cells & plasma
29
What does Aspirin do?
Increases breathing rate and expiration of CO2 to attempt to normalize excess H concentration
30
What is ketoacidosis?
Insulin supply is inadequate (due to autoimmune destruction of B-cells of pancreas), so body stays in a state similar to fasting even with food ingestion (insulin is not signaling uptake of glucose into tissues, so ketones are still being formed); ketones are weak acids that release anions and hydrogen ions which thereby lower the blood pH
31
What do we use for PO2 analysis?
Clark electrode
32
What do we use for PCO2 analysis?
Severinghaus
33
What is 60% of our body weight?
Water
34
What does buffer resist?
Changes in pH
35
How is water distributed?
Intracellular & extracellular components
36
Acids release
H
37
Bases accept
H
38
What does normal metabolism generate?
Metabolic acids, inorganic acids, and CO2
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Hemoglobin acts as a
Buffer
40
Respiratory acidosis
CO2 elimination is inadequate
↑ PCO2
↓ pH because [H+] increases
If chronic, [HCO3 ] increases
Accumulation of CO2, push toward right
41
Respiratory alkalosis
CO2 elimination is excessive
↑ pH because [H+] decreases
↓ PCO2
If chronic, [HCO3-] decreases
CO2 decrease, push toward left
42
Metabolic acidosis
↓ pH because [H+] increases
↓ [HCO3 ]
If chronic, PCO2 decreases
Administration of HCO3 can provide temporary palliation.
Accumulation of H in blood
43
What is the general structure of amino acids?
Carboxylic acid group, amino acid group attached to an alpha-carbon in L configuration, hydrogen atom, and varying side chains
44
What is the ionization state of amino acids at physiological pH?
They are zwitterions
Amino group + charge, carboxylate group - charge
45
Why does glycine not fit well into any amino acid classifications?
Small hydrogen chain, which causes the least amount of steric hinderance
Usually found at bends in proteins
46
Which amino acids are nonpolar hydrophobics?
Alanine, valine, leucine, isoleucine, proline
47
Which amino acids are uncharged polar?
Serine, threonine, asparagine, glutamine
48
Which amino acids are considered "sulfur"
Cystine, methionine
49
Which amino acids are negatively charged (acidic)?
Aspartate, glutamate
50
Which amino acids are positively charged (basic)?
Lysine, arginine, histidine
51
Which amino acids are aromatic?
Phenylalanine, tyrosine, trytophan
52
What are the 9 essential amino acids for the body?
Leucine, isoleucine, lysine, threonine, valine, tryptophan, phenylalanine, methionine, and histidine
53
Phenylalanine is very... and ...
Nonpolar, hydrophobic
54
Tyrosine has ... group that engages in ... bonds/hydrophilic
Hydroxyl, hydrogen
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Tryptophan is an indole ... with ... that can hydrogen bond
Ring, nitrogen
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What does not occur with the H atoms on the aromatic amino acids?
Hydrogen bonding
57
Which sulfur amino acid forms disulfide bridges?
Cysteine
58
What occurs when a pH is higher than 10 in positively charged amino acids?
Lose the proton from NH group
59
What occurs when a pH is lesser than four in negatively charged amino acids?
Lose the proton from carboxylic acid
60
Methionine (sulfur) is nonpolar, large, and has a bulky side chain. What does it do in place of forming a disulfide bridge?
Transfers methyl group that was attached to the sulfur atom
61
What do uncharged amino acids contain?
Hydroxyl or amide group
62
Asparagine and glutamine are amides of...
Aspartate and glutamate
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Where can you find uncharged polar amino acids?
On the surface of water-soluble globular proteins
64
Nonpolar amino acids...
Cluster together for the hydrophobic effect
65
What is unique about proline?
An amino acid due to ring involving a-carbon and a-amino group, forms kinks in peptide backbones or restrictions of conformation
66
What do valine, leucine, and isoleucine exhibit?
High hydrophobicity!
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What are the chemical properties of a peptide bond?
* Between carboxylic acid group and amino group of next acid
* Amino group, a-carbon, and carboxyl group form peptide backbone with side chains extending outwards
68
Primary structure of amino acids can ... the translated protein structure ...
Alter, therefore alter protein function
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What does the primary structure assume?
Trans configuration -> successive alpha-carbons and R groups are on opposite sides
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What must remain planar in the primary structure?
Carboxyl & amide groups
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What can occur in primary structure?
Variations
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What is found in variant regions?
Noncritical variations of the primary amino acid
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What is considered a conservation substitution?
Replacing one amino acid with one of a similar structure
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If many different amino acid residues are tolerated at a certain position, it is called...
Hypervariable
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Regions where binding sites or functional three-dimensional structures are usually...
Invariant
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What are common post-translational modifications?
Phosphorylation, oxidation, carboxylation, glycosylation, fatty acylation/prenylation, regulatory modification, oxidation/hydroxylation of proline, selenocysteine
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O-glycosylation
Small chains bound to serine or threonine residues by O-linkage, attached in secreted proteins
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N-glycosylation
Bound by N-linkage to the amide nitrogen of asparagine, in order to protect from proteolysis or immune attack
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Fatty acylation/prenylation
Addition of lipid, found in many membrane proteins
80
Phosphorylation of hydroxyl group on serine, threonine, or tyrosine by protein kinase
Large, bulky, negatively charged group created altering structure and activity
81
Where does acetylation occur?
Lysine residues of histone proteins in chromatin
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Adenosine diphosphate ribosylation
Transfer of ADP ribose from NAD+ to arginine, glutamine, or cysteine residue, regulating the activity
83
Carboxylation of gamma-carbon of glutamate
Attaching clot to surface; mediated by calcium ions binding two negatively charged carboxyl groups to phospholipids of cell membrane
84
Oxidation/hydroxylation of proline
Hydroxyproline found in collagen, with proline containing hydroxyl group bound to proline which increasing hydrogen bonding and stabilizes structure
85
What is not a true posttranslational modification?
Selenocysteine
86
What is cystinuria?
A genetically inherited amino acid substitution in this transport protein (normally reabsorbs cystine, arginine, and lysine) resulting in high amounts in urine. Since cystine is less soluble and precipitates to form renal stones/calculi
87
What are the chemical forces that govern protein structure?
Covalent bonds, hydrogen bonding for alpha-helices and beta-sheets, combo of ionic interactions, hydrophobic effects, hydrogen bonding, and van der Waals forces
88
What is the primary structure of proteins?
Linear sequence of amino acids in polypeptide chain
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What is the secondary structure of proteins?
Alpha-helices, beta-sheets (repetitive patterns of hydrogen bonds)
90
Alpha-helices
Hydrogen bond between carbonyl oxygen and amide hydrogen of AA four residues down with side chains projecting back and out (proline is helix breaker)
91
Beta-sheets
Hydrogen bonding between neighboring strands that are parallel, and carbonyl oxygen of one is bonds to amide hydrogen of adjacent (usually pleated)
Can run in parallel, antiparallel
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What is the tertiary structure of proteins?
Folding of secondary into overall conformation (hydrophobic core and hydrophilic surface), made of structural domains (nucleotide bonding fold, or actin fold)
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Actin fold
ATP bound to middle of cleft of actin fold which promotes conformational change
94
Nucleotide-binding fold
Single domain, binding site for NAD+
95
What is the quaternary structure?
Two or more subunits of a protein
Protomer/multimer: multiple different subunits
Oligomer: identical subunits
96
How do globular proteins resemble?
Irregular balls, soluble in aqueous medium
97
How do fibrous proteins resemble?
Geometrically linear, arranged around a single axis, and having a repeating unit structure
98
What is usually in transmembrane proteins?
Proteins that have one or more regions aligned to cross the lipid membrane
99
What is the structure of myoglobin?
Globular protein composed of single polypeptide chain with one oxygen binding site
100
What is the structure of hemoglobin?
A tetramer with two different subunits (aB-protomer), each subunit with its own oxygen binding site
101
What type of curve occurs for myoglobin?
Hyperbolic curve
102
What type of curve occurs for hemoglobin?
Sigmoidal curve
103
At lower oxygen levels, what does myoglobin picks O2 from?
Hemoglobin
104
What does 2-3 biphosphoglycerate do in oxygen-binding to hemoglobin?
Binds to hemoglobin in central cavity and increases energy required for conformational changes, decreasing affinity and releasing O2
105
What happens when blood enters tissue?
pH of blood decreases due to CO2 and carbonic acid reaction, promotes release of oxygen
106
What structure determines protein folding?
Primary structure
107
What occurs during protein folding?
Not always completed on their own, can use heat-shock/chaperonin proteins which use ATP hydrolysis to assist with folding, especially through high energy conformations
Other isomerases can also assist with folding or differentiation into other stable isomers
108
What is protein denaturing?
Unfolded/broken, losing overall structure
109
What is an example fo protein denaturing?
Urea disrupts hydrogen bonds, converting protein into soluble random coil
110
What can occur to denatured proteins?
Refold if not precipitated into aggregates
111
What is prion disease?
Neurodegenerative disease that templates as misfolding and aggregation of normal cellular proteins
112
When can proteins by denatured?
Changes of pH, temperature, or solvent that disrupt ionic, hydrogen, and hydrophobic bonds
113
What does prion stand for?
Proteinaceous infectious agent
114
How does prion disease form?
Acquired through infection or from sporadic or inherited mutations
115
What is the most common form of prion disease?
Sporadic
116
When does prion disease occur?
The infectious disease occurs with the ingestion of PrPSc dimers in which the prion protein is already folded into the high β-structure
117
What occurs in sickle cell anemia?
Abnormal quaternary structure due to valine know which binds successive molecules in long fibers
118
What are the symptoms of sickle cell anemia?
Red blood cells become sickle-shaped which results in clogging of capillaries and ischemia, resulting in pain, likewise spleen destroys these cells resulting in overall anemia
119
What occurs is malaria?
Caused by parasite plasmodium falciparum, affects red blood cells developing protrusions that attach to lining of capillaries occluding vessels
120
IN HbS infected cells, what easily recognizes and destroys the cell?
Spleen
121
What is isozyme?
Proteins that differ somewhat in primary structure and properties from tissue to tissue
122
What is creatine kinase used for?
MB can be utilized to diagnose tissue injury and cell death in heart
123
What is troponin used for?
Cells cannot generate ATP, membranes become damaged, and enzymes leak into blood; detectable in blood measurement
124
What is amyloidosis?
A generic name for the extracellular deposition of pathological insoluble proteins, called amyloid, which are located in organs and tissues. In this chapter, the amyloid is derived from the immunoglobulin light chain. In this disorder, the amyloid will accumulate in the kidney and heart, leading to renal and cardiac-related symptoms
125
Charged amino acids form
Ionic bonds
126
Which protein structure contains a hydrophobic core?
Tertiary
127
What is the most specific marker for evidence of heart muscle damage?
Cardiac troponin - cTnT
128
What is an enzyme?
Proteins that act as catalysts which increase rate of chemical reactions
129
What is within an enzyme?
Contain active catalytic sites which bind specific substrates
Increases in temperature -> increase reaction rate
Usually ends in -ase
130
What are the three enzyme equations?
1. Binding of substrate (a reactant): E + S ↔ ES
2. Conversion of bound substrate to bound product: ES ↔ EP
3. Release of product: EP ↔ E + P
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What does enzyme not do?
Change initial energy of substrates or final energy of product
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Active site is usually...
Cleft or crevice in enzyme formed by one or more regions of the polypeptide chain
133
What is enzyme specificity?
Ability to select just one substrate and distinguish between similar, due to three dimensional arrangement of specific amino acid residues in the enzyme
134
What is the lock and key model?
Substrate bindng site contains arrangement that recognizes substrate and binds it
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What is the induced fit model?
As substrate binds, enzyme undergoes a conformational change that repositions and increases binding interactions, dynamic surface
136
Transition state
Formed within enzyme when substrates have bound and conformational changes have occurred, activating substrates in an unstable high energy complex with strained configuration
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What is the general acid base enzyme?
Functional group on proton either donates or accepts proton
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What is the covalent enzyme?
Substrate is covalently linked to amino acid in active site of enzyme
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What is a metal-ion enzyme?
The enzyme contains metal ions that binds and orient substrates
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What is an approximation enzyme?
Enzyme forces substrates to bind in manner that places reactive groups in appropriate orientation
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What is a cofactor enzyme?
Specific cofactor in enzyme forms covalent bond with substrate
142
What is the role of functional groups in catalysis?
Rely of specific amino acid residues in active site to bind substrate, or can employ cofactors to help
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Which amino acids often participate in catalysis?
Polar amino acids, since they are nucleophilic and stabilize more positively charged groups
144
Activation energy
The difference in energy between the substrate and the transition state-complex
145
What is a coenzyme?
Complex nonprotein organic molecules that catalyze by providing functional groups; usually synthesized from vitamins
146
How do activation-transfer coenzymes participate in catalysis?
Forming a covalent bond with a portion of the substrate
147
Coenzymes have very little...in the absence of enzyme and very little...
Activity, specificity
148
Activation-transfer coenzymes
Holds substrate tightly for next reaction step, depends on enzyme for additional specificity and catalytic power
149
Oxidation-reduction coenzymes
Has unique functional group that accepts and donates electrons
150
Metal ions can uniquely
Bind to multiple ligands (possibly)
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How does pH impact enzyme activity?
Low pH -> too protonated
High pH -> too ionized
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How does temperature impact enzyme activity?
Increase in temperature can increase energy of substrates, but too high and the enzymes will become denatured
153
Mechanism-based inhibitors
Inhibitors that mimic or participate in intermediate step of catalytic reaction
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Covalent inhibitors
Form covalent bonds with function groups in the catalytic site, often irreversible
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Transition state analogs
Potent and specific inhibitors of enzymes, bind very tightly, resemble intermediate state of reaction more closely than substrate
156
Heavy metal inhibitors
Cause heavy metal toxicity by tight binding of metal to functional group of enzyme
Examples: mercury, lead, aluminium, iron
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What type of enzyme inhibition occurs in malathion?
Covalent inhibitor
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What mechanism of action is the enzyme inhibition of malathion?
An organophosphate
o Metabolized in lever to malaoxon, which binds to active site serine in enzymes, prevents breakdown of Ach which overstimulates autonomic nervous system
o Form a covalent intermediate in active site, preventing enzyme from degrading into product
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What type of enzyme inhibitor is penicllin?
Transition state analog
160
What is the mechanism fo action for penicillin?
o Binds tightly to glycopeptide transferase which synthesizes cell wall in bacteria
o Strong resemblance between peptide bond in B-lactam ring and transition state complex of natural transpeptidation reaction
o Also referred to as suicide inhibitors
161
What type of enzyme inhibitor is allopurinol?
Induced transition state analog
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What mechanism does allopurinol do?
o Inhibits xanthine oxidase by causing it to oxidize allopurinol to oxypurinol which then binds very tightly to Mo-S complex in active site
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If the enzyme is doubled...
Velocity is doubled
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As substrate increases...
Velocity increases, slightly closer to Vmax (due to saturation)
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What is Vmax?
Max velocity that can be achieved with infinite substrate concentration
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What is Km?
Concentration of substrate required to reach 1/2 Vmax
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What is most sensitive to changes at substrate concentrations?
v
168
What is the Michaelis-Menten equation?
v = Vmax [S] / Km + [S]
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Competitive inhibition
o Competes with substrate for binding of the enzymes active site
o Usually a close structural analog of substrate
o Increase in substrate concentration can overcome competitive inhibition
o Increase the apparent Km of the enzyme because they raise the concentration of substrate necessary to saturate, but no effect on Vmax
170
Noncompetitive inhibition
o Binds to an inhibition site that does not affect the binding of other substrate
Can be in a multisubstrate enzyme that binds to only one of the substrate sites, or a metal inhibitor that binds to a different site affecting both substrates
o Lower concentration of active enzyme and therefore decreases Vmax, but does not change Km
171
In a Lineweaver Burk plot, what is the X intercept? The Y intercept? What is the slope?
X intercept -> -1/Km
Y intercept -> 1/Vmax
Slope -> Km/Vmax
172
What is an allosteric enzyme?
Compounds that bind to allosteric site causing conformational change affecting affinity of enzyme for substrate
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What do allosteric enzyme activators do?
Increase affinity for substrate, bind more tightly to relaxed state than taut state
174
What do allosteric enzyme inhibitors do?
Decrease affinity for substrate, bind more tightly to taut state than relaxed
175
What are three examples of covalent modification?
Phosphorylation, muscle glycogen phosphorylase, protein kinase A
176
What is phosphorylation?
Protein kinases transfer phosphate from ATP to hydroxyl group on target enzyme amino acid residue, which causes conformational change affecting activity of enzyme; can be reversed by protein phosphatase
177
What is muscle glycogen phosphorylase?
Can be activated allosterically by AMP, or through phosphorylation by glycogen phosphorylase kinase
178
What is protein kinase A?
Phosphorylates several enzymes that regulate different pathways; hormonal control by epinephrine and other hormones increases CAMP which binds to regulatory subunits of protein kinase A, causing release of inhibitory regulatory subunits
179
What are protein-protein interactions?
CA2+-calmodulin & G-proteins
180
What is Ca2+-calmodulin?
Dissociable modulator protein that binds to several proteins regulating their function; neural impulses triggers Ca release from SR to initiate
181
What is a G protein?
Small single subunit proteins that bind GTP which allows them to bind to target protein for inhibition or activation, hydrolysis of attached GTP forces dissociation of G protein and target protein, GDP can be phosphorylated again and process can restart
182
What is proteolytic cleavage?
Precursor proteins of proteases are released as zymogens, which are activated by cleaving off small peptide from peptide structure
183
What changes with amount of enzyme?
Vmax -> increased protein synthesis or increased degradation
184
How are metabolic pathways regulated?
Rate limiting step, feedback regulation, feed-forward, tissue isozymes of regulatory proteins, counter-regulation of opposing pathways, and substrate channeling through compartmentalization
185
What is the rate-limiting step?
Rate-limiting enzyme, slowest step of reaction, not readily reversible; inhibition of this usually leads to accumulation of pathway precursor
186
What is feedback regulation?
End product of pathway controls its own rate of synthesis; usually allosteric regulation of rate limiting enzyme or by inducing/repressing gene transcription
187
What is feed-forward?
Increased supply of substrate causes allosteric activation of rate limiting enzyme, substrate induction of gene transcription, or increased concentration of hormone which stimulate enzyme phosphorylation; often disposal of toxic compounds
188
What is tissue isozymes of regulatory proteins?
Specific tissues use certain isozymes for certain functions in each tissue
189
What is counter-regulation of opposing pathways?
Inhibition of one pathway while other is activated
190
What is substrate channeling through compartmentalization?
Similar enzymes or pathways are compartmentalized into organelles (TCA located within mitochondria) or formation of multienzyme complexes that can transfer from one enzyme to next more easily
191
What occurs in malathion poisoning?
Inhibition of acetylcholinesterase at neuromuscular junctions
192
What is typically elevated in liver disease?
AST, ALT
193
What is typically elevated in pancreas disease?
Amylase, lipase
194
What is elevated in myocardial infarction?
CK-MB
195
What is elevated in myocardial infarction?
CK-MB
196
What does GGT indicate?
Liver disease especially in biliary obstruction
197
When is troponin the most elevated in an acute myocardial infarction?
12 - 18 hours
198
Streptokinase purpose
Activates fibrinolytic enzyme system in order to break down clots
CAN ONLY BE USED ONCE
199
Tissue plasminogen activator (t-PA) purpose
Made from deactivated E.coli
Used to dissolve blood clots after myocardial infarction
200
Asparaginase purpose
Breaks down asparagine for development of certain tumors ie: adult leukemia
201
What does sulphonamides inhibit?
Dihydropteroate synthetase for bacterial infections
202
What does methotrexate inhibit?
Dihydrofolate reductase -> various neoplasms (* leukimia)
203
What does allopurinol inhibit?
Xanthine oxidase -> gout!
204
What ACE inhibitors?
Angiotensin-converting enzyme (high blood pressure)
205
What does warfarin inhibit?
Glutamate carboxylase -> thrombosis
206
What do statins inhibit?
HMG-CoA reductase
Elevated plasma cholesterol
207
What does omeprazole and esomeprazole inhibit?
H+K+-ATPase -> gastric reflux
208
What does aspirin inhibit?
Cyclo-oxygenase -> inflammation, pain, prophylaxis in CAD
