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Biochemistry > Exam 2 Lecture 10 > Flashcards

Exam 2 Lecture 10 Flashcards

1
Q

What is signal transduction?

A

Cell to cell communication

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2
Q

What is the process of signal transduction?

A
  1. Cells receive external signals through receptor molecule (sender cell)
  2. Signal is converted into another chemical form or is transduced
  3. Transduction is often amplified and is regulated by intracellular signaling proteins
  4. A cellular response is created
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3
Q

What are the different cell responses?

A
  1. gene expression
  2. membrane transport
  3. metabolism
  4. cell growth/death
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4
Q

What is the overall idea of signal transduction?

A

Information from the environment that gets transmitted inside a cell generates a cellular response

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5
Q

What is the purpose of signal transduction?

A
  1. coordinate cell metabolism, growth, and development
  2. ensure homeostasis among tissues and organs
  3. response to external stimuli like light, pressure, and heat
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6
Q

What is a signal transduction cascade?

A

Sequential biochemical events that transfer a signal through a series of reactions that activate intermediate molecules and to the final target

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7
Q

What are the three main steps in a signal transduction cascade?

A
  1. reception
  2. transduction
  3. response
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8
Q

What is signal amplification?

A

One signaling molecule on the outside can activate downstream signaling molecules over and over again to create a huge cascade on the inside of the cell and amplify the signal

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9
Q

How do metabolic pathways differ from signaling pathways?

A
  1. Series of enzymatic reactions (in which the product of one reaction is the substrate of the next reaction) to convert a metabolite into one or two other metabolites to synthesize or degrade biomolecules
  2. Can include the transportation of a metabolite from one compartment of the cell to another or even across the plasma membrane
  3. Regulated depending on the needs of the cell and substrate availability
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10
Q

How do signaling pathways differ from metabolic pathways?

A
  1. Have external ligands that trigger intracellular events
  2. Involves the enzymatic modification of a protein (post translational) to alter its conformation, intermolecular interactions, cellular locations, and/or its function
  3. Involves the regulation of gene expression and changes in protein activity
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11
Q

What are the 5 different modes of cell-cell communication?

A
  1. Juxtacrine
  2. Paracrine
  3. Endocrine
  4. Synaptic/neuronal
  5. Autocrine
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12
Q

What is juxtacrine signaling?

A

Is direct cell to cell contact in which two surface proteins bind

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13
Q

What is endocrine signaling?

A

Involves hormones that get secreted into the bloodstream so has no cell-cell contact, has a low concentration (10^-12 to 10^-9 M), and has a high affinity receptor (has to find their target), response can take minutes to hours

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14
Q

What is paracrine signaling?

A

Involves the sender and target cell being nearby one another in which the secreted ligands target nearby cells, has a high local concentration (10^-9 to 10^-6 M), has a low affinity receptor, response is rapid and transient within seconds to minutes

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15
Q

What is the relationship between the affinity of the receptor and the concentration?

A

Direct relationship in which low concentration = high affinity receptor and high concentration = low affinity receptor

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16
Q

What is synaptic/neuronal signaling?

A

Involves the pre-synaptic neuron and the post-synaptic neuron/target cell (which has the receptor) and the synapse between the neuron and target cell is very short distance, has a very high local concentration (10^-6 to 10^-3 M), has a low affinity receptor that dissociates rapidly in milliseconds (has a short life)

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17
Q

Synaptic/neuronal signaling is a special type of what kind of signaling?

A

Paracrine signaling

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18
Q

What is autocrine signaling?

A

The sender and target cell are the same cell (cell is telling itself so there are receptors on itself) and the response time is similar to paracrine signaling which is rapid and transient from seconds to minutes

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19
Q

What are secreted molecules for receptors?

A

They are first messengers and ligands that can be a variety of molecules ranging in size and chemical types

20
Q

What are some examples of large ligands?

A

Proteins and polypeptides

21
Q

What are some examples of small ligands?

A

Amino acids, lipids, and nucleotides

22
Q

What are some examples of other chemical types of ligands?

A

Steroids, vitamins, histamine, and modified amino acids

23
Q

What are some examples of receptors?

A

Intracellular proteins and integral membrane proteins

24
Q

How does the intracellular receptor for steroid hormones, thyroid hormones, and vitamins work?

A

Hormones are lipid soluble (hydrophobic) so they can diffuse through the membrane and bind to the intracellular receptor → signal gets propagated by changes in the receptor upon binding which can lead to altered gene expression

25
Q

What is an example of an intracellular receptor?

A

Hormonal nuclear receptor in which the hormonal response element is highly specific to the given hormone/nuclear receptor

26
Q

What is another example of an intracellular receptor?

A

Thyroid nuclear receptor

27
Q

What is the mechanism of the thyroid nuclear receptor?

A
  1. Thyroid hormone is lipid soluble so it can diffuse through the plasma membrane
  2. Once inside the cell, the thyroid hormone can bind to the receptor and promote the dimerization of the receptor
  3. Coregulatory proteins are recruited
  4. Promotes DNA binding and specific recognition of thyroid response element (TRE) → affects signaling outcome on transcription
28
Q

Where does the thyroid hormone bind?

A

It binds in the middle of one of the dimers of the ligand binding domain

29
Q

What are the 4 major cell-surface receptors?

A
  1. ligand gated ion channel receptors
  2. enzyme-linked or catalytic receptors
  3. cytokine family receptors
  4. G-protein coupled receptors (GPCR)
30
Q

What are the 3 types of effects of first messenger binding?

A
  1. generation of second messengers
  2. change in the plasma membrane potential
  3. activation of effector-enzyme cascades by direct interaction of receptor or through coupling/transducing proteins
31
Q

What is a second messenger and what does it do?

A

They are typically small, intracellular molecules that transmit and amplify the initial signal from extracellular first messenger binding to receptors

32
Q

What are some examples of second messengers?

A

They can be inorganic ions such as Ca2+ or organic products of enzyme catalyzed reactions

33
Q

What are some examples of water soluble second messengers?

A

cAMP, cGMP, and inositol triphosphate (IP3)

34
Q

What are some examples of lipid soluble second messengers?

A

diacylglycerol (DAG) and PIP3

35
Q

What does downstream signaling control do?

A

It’s a mechanism to control protein-protein interactions and enzymatic activity

36
Q

What does phosphorylation of a protein do?

A
  1. It can induce a conformational change like catalytic activity that results in an altered function
  2. It can promote protein-protein interaction in which the phosphorylated residue in the binding site is recognized by a binding partner but the unphosphorylated one is not
37
Q

What enzymes are needed for phosphorylation?

A

Kinases will phosphorylate a protein using ATP and a phosphatase will remove a phosphate group and dephosphorylate the protein

38
Q

What is a scaffold and what is its importance?

A

They are large assemblies of proteins that form under the control of phosphorylation and can relay a message much faster than waiting for a protein to float by and relay the message

39
Q

What is another example of a downstream signaling control?

A

GTP binding regulatory proteins (GTPases)

40
Q

What do G proteins do?

A

They bind and hydrolyze GTP and the GDP bound form has a different conformation than the GTP bound form

41
Q

The exchange of GDP for GTP is catalyzed by what enzymes?

A

Guanine nucleotide exchange factors (GEFs) → can be coupled to GPCR and GPCRs can act as GEFs

42
Q

If GTP is bound

A

Signal is turned ON

43
Q

If GDP is bound

A

Signal is turned OFF (hydrolysis turns off the signal)

44
Q

Ras proteins are

A
  1. not trimeric
  2. small GTPase/monomeric G-protein that functions in cell proliferation and protein synthesis
  3. bad things happen when it has mutations because it could become oncogenic
  4. Small and soluble
45
Q

How are cell surface receptors turned off to terminate signaling?

A
  1. Rapidly reduce the level of the message/agonist availability in the extracellular vicinity of the target cell (common for synaptic signaling)
  2. Receptor loss/desensitization
46
Q

How can you reduce the level of message to terminate signaling?

A
  1. Rapid re-uptake of neurotransmitters by transporters (like serotonin, dopamine, SERT!)
  2. Breakdown by enzymes (acetylcholine esterase)
47
Q

How can receptor loss or desensitization occur?

A
  1. Reduced receptor availability by internalization (endocytosed) or degradation of the agonist bound receptor complex
  2. Functionally adapted by modifying receptors to be less sensitive (by phosphorylation or dephosphorylation)

Biochemistry (18 decks)

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