Week 3 Flashcards
(144 cards)
1
Q
In what ways are enzyme-catalyzed reactions are controlled by regulatory enzymes?
A
- When a particular substance is needed, reaction increases
2. When a substance is not needed, reactions rate decreases
2
Q
What is the benefit of controlling the rate of metabolic pathways?
A
Allows cells to adapt to its changing needs
3
Q
Why does an enzyme rate depend on substrate concentration?
A
The higher the concentration, the faster the reaction until active sites are fully saturated.
4
Q
What controls the rate of a metabolic pathway at the right place and time?
A
Regulation enzymes
5
Q
What are the two mechanisms of regulating enzyme activity?
A
- Control of catalytic efficiency through protein modification
- Bioavailability
6
Q
What are 5 ways enzymes are regulated?
A
- Allosteric control (non-covalent)
- By having multiple forms of enzymes (isozymes)
- Reversible covalent modification (transfer of phosphoryl groups)
- Proteolytic Activation (zymogens)
- Controlling amount of enzyme present (transcriptional level)
7
Q
How is enzyme activity controlled?
A
Inhibition by enzyme inhibitors
8
Q
Differentiate between allosteric activators and inhibitors
A
Activators increase the affinity of the enzyme for a substrate by binding to the T state and conformational changes the enzyme to an R state.
Inhibitors bind more tightly to the T state making it difficult for subunits to be in a more active conformation
9
Q
What are examples of allosteric activators?
A
AMP and ADP indicate low energy state and the need to turn on enzymes to generate ATP
It is a rapid process
10
Q
How do you overcome the effects of the allosteric inhibitor?
A
- Increase in substrate concentration
2. Increase in activator concentration
11
Q
What is the purpose for allosteric site?
A
Apart from the active site, it causes conformational change that affects enzymes affinity for the substrate
12
Q
What is a homotropic effectors?
A
- Presence of substrate in one active site enhances the catalytic properties at other binding sites (positive cooperativity)
- Most function as allosteric activators
- When an enzyme’s substrate serves as an effector
13
Q
What are heterotropic effectors?
A
- Different from the enzyme substrate
- Ligand binding to the allosteric site has a different purpose than a ligand binding to the active site
- Most function as allosteric inhibitors
- Important to feedback mechanisms where products from downstream reactions feedback and affect allosteric enzyme activity
14
Q
Explain positive cooperatively
A
When the binding of a substrate to one subunit facilitates the binding of a substrate to another subunit
15
Q
What is the “T” conformation?
A
Low affinity for substrate (inactive state)
16
Q
What is the “R” state
A
High affinity for substrate (active state)
17
Q
What is the purpose for allosteric enzymes?
A
- Rate limiting enzymes in metabolic pathways
2. Junctions between different pathways that use the same substrate
18
Q
What are isozymes?
A
Enzymes that catalyze the same reactions but have different physical properties
19
Q
What is the difference between glucokinase and hexokinase?
A
- Glucokinase has low affinity for glucose and found in the liver
- Hexokinase has high affinity for glucose and found in RBCs, skeletal muscles, and most tissues
20
Q
What is lactate dehydrogenase and does it express isozymes?
A
- Utilized for pyruvate to lactate reactions (anaerobic) and lactate to pyruvate (aerobic)
- Has 5 isozymes revealing tissue specificity differing in structure and kinetic properties
21
Q
What mechanism regulates most enzymes?
A
Phosphorylation
22
Q
What enzyme carries out phosphorylation?
A
Protein kinase
23
Q
What enzyme carries out dephosphorylation?
A
Protein phosphatase
24
Q
What enzyme transfers a phosphate group from ATP to OH group of serine on target enzyme?
A
Serine/threonine kinases
25
What enzyme transfers a phosphate group to the hydroxyl group of a specific tyrosine residue?
Tyrosine kinases
26
What are the key features of phosphorylation?
1. The addition of the phosphoryl group alters electrostatic interactions
2. A phosphoryl group can form H-bonds
3. Phosphorylation and dephosphorylation occurs rapidly
4. Phosphorylation can be used to amplify signals
5. Kinases use ATP as the source of phosphate groups
27
Explain glycogen phosphorylase
- Rate limiting enzyme in glycogen degradation (glycogen to G1P)
- Activated by phosphorylation of Ser side chain
- Inactivated by dephosphorylation of Ser residues
28
Explain Proteolytic Activation-Zymogens
An irreversible regulation where zymogens most undergo proteolytic cleavage to become fully functional does not require energy to cleave
29
What is a zymogen?
An inactive precursors of enzymes
30
Describe the process of activating chymotrypsinogen?
1. Chymotrypsinogen is stored in the pancreatic cell and secreted into the intestinal lumen
2. By proteolytic enzyme trypsin, chymotrypsinogen converts to a-Chymotrypsin
3. Enzyme cleaves primary structure cause tertiary structure to cleave as well
4. a-chymotrypsin actives
31
Give a brief explanation of the blood clotting cascade
1. Fibrinogen and prothrombin circulate in the blood in the inactive form
2. They are cleaved by proteases to active form
3. Proteases are activated by their attachment to a damaged region in the vessel wall
4. Keeps clot formation to site of injury and not in circulation
32
What factors effect maximal capacity of a tissue change?
1. Increased protein synthesis
| 2. Increased protein degradation
33
How would you increase the velocity of a reaction?
Increase the amount of enzyme present to convert substrate to product
34
What is the difference between induction and repression?
Induction is the increase in rate, repression is the decrease in rate of gene transcription
35
Is regulated enzyme synthesis a slow or rapid process?
Slow – hrs to days
36
What is an example of induction?
Cytochrome P450-2EI oxidizes ethanol in alcohol. Increased in the liver with increased ingestion of alcohol relaying to the induction of gene transcription.
37
Explain what protein degradation is in regards to fasting
Protein degradation in skeletal muscles are activated to increase amino acid levels in blood
38
Explain what protein degradation is in regards to infection
Degradation is used to liberate amino acids to produce antibodies and other proteins for the immune response
39
What enzymes are involved with lysosomal degradation?
Acidic proteases and hydrolases
40
What is a ubiquitin-proteasome system?
Attachment of a ubiquitin polypeptide to proteins targeted for degradation by proteasome
41
What are the principles of pathway regulation?
1. Metabolic pathways are a series of sequential reactions
2. Product of one reaction is the substrate for another
3. Pathways have branch points where intermediates become precursors for another pathway
42
Explain rate limiting step
- Pathways are regulated by one key enzyme-regulatory enzyme
- Slowest step and not easily reversible
- 1st committed step of a pathway
- Changes in this step can influence the rest of the pathway
43
What happens when there is high end product?
Product binds to regulatory enzyme and of pathway and inhibits the formation of intermediate substrates in pathway
44
What happens when there is low end product?
The allosteric inhibitor dissociates from the allosteric site allowing the regulatory enzyme to become active again
45
Why do cells compartmentalize enzymes?
1. Provide unique conditions
2. Limit access of enzymes to substrates
3. Separates anabolic pathways from catabolic ones
46
Define inhibitors
Substances that decrease the rate of an enzyme-catalyzed reaction by binding to the enzyme
47
Describe reversible inhibitors
Substance non-covalently bind to E or ES are subsequently released
48
Explain competitive inhibition
Competes with substrate for binding in the active site by binding to the active site
49
How is competitive inhibition overcome?
Increasing concentration of substrate
50
Why is Statin drugs considered competitive inhibitors?
Inhibits the rate-limiting step of cholesterol synthesis
Statin binds to HMG CoA reductase inhibiting the formation of cholestrol
51
Why are Saquinavir and Indinavir considered competitive?
Mimics the natural Phe-Pro substrate cleaving viral protein from active sites
52
Explain uncompetitive inhibition
Does not compete with substrate because it only binds to ES complex
53
Why can’t you overcome inhibition by increasing substrate concentration?
An increase in [S], increases ES complexes leading to more inhibitor binding
54
Explain noncompetitive inhibition
Can bind to both E or ES complex
Causes conformational change of the enzyme affecting the affinity of the E for the substrate reducing overall functionality of enzymes
55
Describe irreversible inhibitors
Substances cause covalent alterations of enzyme causing it to permanently shut down
They are unreactive until bound to an active site
56
What are important roles of lipids?
1. Energy storage
2. Cell membranes
3. Endocrine signaling
57
What does amphopathic mean?
Molecule that has one end with a polar water-soluable group and another end with a nonpolar hydrocarbon group
58
List the open-chain lipid compounds
- Fatty acids
- Triacylglycerols
- Sphingolipids
- Phosphoacylglycerols
- Glycolipids
59
Explain the structure of fatty acids?
Unbranched carboxylic acids with hydrocarbon chains containing even numbers 4-36 carbons
60
What are examples of fatty acids?
- Unsaturated
- Saturated
- Monounsaturated
- Polyunsaturated
61
What is the difference between unsaturated and saturate?
Unsaturated: Contains carbon-carbon bonds
Saturated: No double bonds between carbons in the chainW
62
What is the difference between unsaturated and saturate?
Unsaturated: Contains carbon-carbon bonds
Saturated: No double bonds between carbons in the chainW
63
What is the difference between monounsaturated and polyunsaturated?
Mono: One double bond between carbons in the alkyl chain
Poly: More than one double bonds in the alkyl chain
64
What form of unsaturated fat is the most predominate?
cis
65
How are the degrees of saturation related to the melting point?
Greater the degree of unsaturation, lower the melting point
66
How does trans fatty acids form?
Partial dehydrogenation of unsaturated fatty acids
67
How is trans fat different from cis fat?
Increased shelf life and stability at high temperature of oils
68
What makes unsaturated cis fatty acids less orderly than saturated?
Its double bond kink
69
What are the three major types of lipid components?
1. Glycerophospholipids
2. Sphingolipids
3. Chloesterol
70
Describe the structure of a glycerophospholipids
1. One or more fatty acids
2. Glycerol backbone
3. Polar he'd group
71
What is the major component of most eukaryotic cell membranes?
Phosphatidylcholine
72
What is the function of sphingolipids?
Plays a role in cell signaling transduction
73
What is a glycolipids?
Located on the extracellular surface of the cell membrane that assists with cell-cell recognition
74
What is the cerebrosides?
The simplest glycolipids containing only a single sugar
75
What is a ganglioside?
A branched chain of as many as 7 sugar molecules
76
What is a sphingomyelin?
Found in the plasma membrane of many cells but is enriched in nerve cells
77
Describe the structure of cholesterol
Contains 27 carbons and a rigid four-ring steroid core
78
What is the function for cholesterol?
1. Affects the fluidity and permeability of the membrane
2. Absent in prokaryotic and fungal cells
3. Serves are a precursor for steroid hormones and bile acid
79
List the fused-ring lipid compounds
- Cholestrol
- Steroid hormones
- Bile acids
80
What part of the membrane is hydrophobic?
Fatty acid portion
81
What part of the membrane is hydrophilic?
Polar head group
82
What are the examples of amphipathic molecules?
1. Micelles
2. Lyposomes
3. Bilayers
83
What determines the amphipathic lipid molecule structure?
1. Type of lipid
| 2. Concentration
84
Describe the structure and function of a micelle
Forms in the solution of amphipathic molecules that have larger, more polar head than tail
Important in intestinal digestion
85
What forms a lipid vesicles?
Small bilayers will spontaneously seal into spherical vesicles in a concentration-dependent manner
86
What makes lipid vesicles different than miscelles?
They had 2 polar heads with an aqueous cavity
87
What stabilizes the plasma membrane?
van der Waals interactions between hydrophobic tails
88
How do membrane lipids provide compartmentalization?
1. Separates energy-producing reactions from energy-consuming ones
2. Keeps proteolytic enzymes away from important cellular proteins
3. Allows for generation of a proton gradient to support ATP synthesis
89
Where is the membrane lipid synthesized?
SER
90
What are the important functions of the plasma membrane?
1. Lipid composition affects flexibility
2. Define the boundaries of the cell
3. Allow import and export
4. Retain metabolites and ions within the cell
5. Sense external signals and transmit information into the cell
6. Provides compartmentalization within the cell
91
Why is the plasma membrane considered asymmetrical?
1. Some lipids are found inside and outside
2. Glycolipids are found on the outer leaflet
3. Can be polarized
92
List 2 proteins that can either be embedded in or associated with the membrane
1. Integral
| 2. Peripheral
93
What are integral proteins?
Firmly associated with the membrane spanning the bilayer
94
What are peripheral proteins?
Proteins that are weakly linked to membrane lipids by anchors or covalently attached to membrane
95
What does the lipid composition of membranes vary by?
1. Organisms
2. Tissues
3. Organelles
96
In what ways do the ratio of lipid to protein vary?
1. Type of phospholipid varies
2. Abundance of cholesterol varies
3. Prokaryotes lack of sterols
4. Cholesterol is predominant in the plasma membrane, absent in mitochondria
97
What holds together the lipid bilayer?
Noncovalent
98
What type of molecule predominates in the outer layer?
Bulkier
99
What type of molecule predominates in the inner layer?
Smaller
100
What side of the membrane is more positively charged?
The outer layer
101
What causes the pause transition of membranes?
Heating
102
In physiological conditions is the membrane more fluid or gel-like?
Fluid
103
Describe the function of saturated fatty acids in the membrane
Provides membrane rigidity
104
Describe the function of unsaturated fatty acids in the membrane
Causes disorderly packing leading to fluidity
105
Describe the function of cholesterol in the membrane
Disrupts the tight packing of fatty acids, sandwiched between saturated fatty acids
106
What happens in lateral diffusion
Lipids and proteins can diffuse laterally in the bilayer
107
What happens in transverse diffusion?
A 10 day process where the phospholipid spontaneously flips from 1 leaflet to another
108
Why is transverse diffusion a slow process?
Charged head group must transverse the hydrophobic tail region of the membrane
109
What is flippases?
An enzyme that uses energy of ATP to regulate membrane fluidity
Catalyzes transverse diffusion
110
What is purpose of a lipid raft?
- Allows segregation of proteins in the membrane
- Important for cell signaling
- Moves as 1 unit
111
What are different types of receptors that detect signals from the outside?
1. Light (opsin)
2. Hormones (insulin receptor)
3. Neurotransmitters (acetylcholine receptor)
4. Pheromones (taste and smell receptors)
112
What are examples of channel proteins?
1. Maltoporin: nutrients
2. K-channel: ions
3. Serotonin reuptake protein: neurotransmitters
113
How do you remove an integral protein?
Breaking apart the membrane
114
What is the difference between monotonic and polytopic?
Mono: interacts with 1 leaflet
Poly: interacts with both leaflets
115
What is a bacteriorhodopsin?
A polytopic integral protein containing membrane spanning alpha helices
116
What is function of b-sheets in the membrane?
Curl up and form a hollow cylinder that serves as a pore or channel
117
Are most transmembrane segments hydrophobic or philic?
Hydrophobic
118
What amino acids are predominant at the non polar/polar interface?
Tyr and Trp
119
What domain are charged amino acids found regarding the membrane?
aqueous
120
What bonds are associated with the peripheral proteins?
1. Electrostatic interactions
| 2. Hydrogen bonds
121
How can peripheral membranes be held by lipid anchors?
1. Con covalently linked to the extracellular or cytoplasmic side
2. GPI anchor
3. Thioester linkage
4. Myristoyl linkage
122
What are amphitropic proteins?
Obtains an affinity for both lipid and aqueous environments
123
How are amphitropic proteins regulated?
Attaching or cleaving from lipids in the membrane
124
What is a function of lipid bilayer's hydrophobicity?
The ability of small molecules to cross the membrane
125
What type of substances has low membrane permeability?
Ions and polar molecules (not water)
126
What does it mean to have a permeability barrier?
Membrane proteins allow transport of molecules and information across the membrane
127
In what ways would transport across a membrane be energetically favorable?
1. Solute moves toward equilibrium across the membrane
| 2. The solute moves toward charge equilibrium across the membrane
128
What is the meaning of passive transport?
Moves solute down its concentration gradient
129
What is simple diffusion?
Molecule or ion moves through an opening or pore in a membrane without a carrier or energy
130
What is facilitated diffusion?
Substances entering cells by binding to transporters and channels
131
What is the importance of ion channels?
Speeds up the passage of inorganic ions across the membrane
132
What is an aquaporin?
A tetramer of identical submits with a transmembrane pore that forms hydrophilic transmembrane channels allowing rapid and bulk transport of water
133
What accompanies energy change for passive diffusion?
A hydrophilic solute through the lipid bilayer of a biological membrane
134
Is the removal of the hydration shell endergonic or exergonic?
endergonic with a high activation energy
135
How a transport protein reduce activation energy?
By forming non covalent interactions with the dehydrated solute to replace the hydrogen bonding with water and by providing a hydrophilic transmembrane pathway
136
What species produces ionophores?
Bacteria and fungi
137
What are ionophores?
Hydrophobic peptide toxin that surrounds an ion and shuttles the ion across the membrane
138
What are some antibiotics that act as ionophores?
Valinomycin and Monesin
139
Describe glucose transport
1 Glucose in blood plasma binds to a stereospecific site on T1; this lowers the activation energy for
2. A conformational change from glucoseout • T1 to glucosein • T2, effecting the transmembrane passage of the glucose.
3. Glucose is released from T2 into the cytoplasm
4. The transporter returns to the T1 conformation, ready to transport another glucose molecule.
140
How is bicarbonate transporter an antiport?
For each HCO3- ion that moves in one direction, a Cl- ion moves in the opposite direction.
Allows the entry and exit of bicarbonate without changing the membrane potential (electroneutral exchange)
141
What is active transport?
Substance moving against its concentration gradient involving a carrier protein requiring energy
142
What is primary active transport?
Transport is directly linked to the hydrolysis of a high-energy molecule, such as ATP
Energy released from ATP hydrolysis drives (“pumps”) solute movement against an a gradient
Sodium–potassium ion pump (Na+--K+ ion pump)
143
What is secondary active transport?
Driven by ion gradient generated by primary active transport
Usually antiporters or symporters
Sodium-glucose linked transporter (SGLT) brings Na+ and glucose inside the cell and is driven by ion gradient generated by the Na+/K+ ion pump
144
Describe the process of potassium ion pump
1. Three intracellular Na+ ions bind
2. Triggers ATP binding
3. Phosphoryl group is transferred to the pump and ADP is released causing a conformational change
4. Na+ dissociates
5. Two extracellular K+ ions bind
6. Stimulates dephosphorylation by hydrolysis
7. Pump undergoes conformation change and release K+ ions
