HHP Exam 3

• Cells are _________ coupled and can transmit forces (_________ _________) and _________ can sense and respond to force

  • Force → __________________ → __________________

• Without gravity and loaded movement muscles _________

• After spaceflight, _________ proteins (i.e. proteins of the _________) are lost in disproportionate amounts to other cellular proteins

• Cells are mechanically coupled and can transmit forces (adherens junctions) and proteins can sense and respond to force

  • Force → cell signaling events → expression of proteins

• Without gravity and loaded movement muscles atrophy

• After spaceflight, contractile proteins (i.e. proteins of the sarcomere) are lost in disproportionate amounts to other cellular proteins

Body Mass Index: BMI

• What is it: Screening tool for _______ ________

• Only considers ________ and ________

• BMI equation = ________________________

• Interpret with caution:

• Incomplete information

• Does not quantify ________ or ________ ________ (fat mass vs. fat-free mass, i.e. body fat %)

Body Mass Index: BMI

• What is it: Screening tool for disease risk

• Only considers height and weight

• BMI equation = weight (kg) / height (meters^2)

• Interpret with caution:

• Incomplete information

• Does not quantify fitness or body composition (fat mass vs. fat-free mass, i.e. body fat %)

• Correlation between BMI and disease risk

  • Observational study = measuring and collecting data without ________ ________

  • Study observed:

    • (Increasing/Decreasing) deaths (i.e. decreased survival) with (Increasing/Decreasing) BMI due to ________ and all-cause mortality

• Generally, (increased/decreased) fitness = (increased/decreased) health risk

  • Recently, there has been interests in understanding health risk of _______ _________, but this is still being actively investigated

• Correlation between BMI and disease risk

  • Observational study = measuring and collecting data without experimental manipulation

  • Study observed:

    • Increasing deaths associated with Increasing BMI due to CVD and all-cause mortality

• Generally, increased fitness = decreased health risk

  • Recently, there has been interests in understanding health risk of extreme exercise, but this is still being actively investigated

What is Fitness?

• 5 components of fitness: ______________________

• Cardiovascular Fitness: Measurement of an individual's _______ _______ capacity

• Ability to uptake, transport, and utilize _________

• Quantified by ________ ________

  • L/min or ml/kg/mi

What is Fitness?

• 5 components of fitness: Cardiovascular, muscular strength, muscular endurance, flexibility, body composition

• Cardiovascular Fitness: Measurement of an individual's aerobic exercise capacity

• Ability to uptake, transport, and utilize oxygen

• Quantified by oxygen uptake

  • L/min or ml/kg/mi

Influence of BMI and Fitness on health outcomes?

• Both cardiovascular fitness and BMI are correlated with health outcomes,

• Generally:

  • CF has (positive/negative) health attributes

  • BMI associated with (positive/negative) health attributes

• Common health metrics assessed:

  • ________ disease risk

  • ________ mortality

Influence of BMI and Fitness on health outcomes?

• Both cardiovascular fitness and BMI are correlated with health outcomes,

• Generally:

  • CF has positive health attributes

  • BMI associated with negative health attributes

• Common health metrics assessed:

  • Cardiovascular disease risk

  • All-cause mortality

Influence of BF% and Fitness on health outcomes

• Black bars = ________________________________

• White bars = ________________________________

• RR = ________________________________

• Higher values = ________________________________

Influence of BF% and Fitness on health outcomes

• Black bars = least fit men in each BF% category (lowest quartile of oxygen uptake)

• White bars = fittest men in each category

• RR = relative risk compared to control (fit, lean men)

• Higher values = increased risk of dying from CVD

• Increasing BF% (inc/dec) RR of CVD (increasing height of (black/white) bars)

  • BUT – Fittest men within each category had (inc/dec) risk of CVD ((black/white) bars are shorter than all (black/white) bars)

• Authors conclude: The health benefits of leanness are limited to fit men, and being fit may reduce the hazards of obesity.

• Key takeaway for future health or fitness professionals: De-emphasize the need/focus for _________, encourage _________ even if body weight is unchanging.

  • Sometimes, you just cannot see the positive physiological/cellular changes that accompany _________

• Increasing BF% increased RR of CVD (increasing height of black bars)

  • BUT – Fittest men within each category had decreased risk of CVD (white bars are shorter than all black bars)

• Authors conclude: The health benefits of leanness are limited to fit men, and being fit may reduce the hazards of obesity.

• Key takeaway for future health or fitness professionals: De-emphasize the need/focus for weight loss, encourage PA even if body weight is unchanging.

  • Sometimes, you just cannot see the positive physiological/cellular changes that accompany PA

• Physical Activity: ___________________

• Physical Inactivity: the inverse of physical activity

• Quantitatively inactivity would be less than ______________ (< (#) minutes / week)

  • If (#)% Americans report meeting activity recommendations, then (#)% of Americans quantitively considered inactive

• Physical Activity: any bodily movement

• Physical Inactivity: the inverse of physical activity

• Quantitatively inactivity would be less than activity recommendations (< 150 minutes / week)

  • If 25% Americans report meeting activity recommendations, then 75% of Americans quantitively considered inactive

The Dallas Bed Rest Study (1966)

• 5 healthy 20-year-old men

• (#) weeks at complete bed rest with no weight bearing allowed

  • At the time, standard patient care protocol after ___________

• "Thus, 3 weeks of bed rest at age 20 years reduced ___________ capacity more than (#) years of aging."

• Altered the way heart attack patients cared for

  • Encouraging ___________ and ___________ rehabilitation programs

The Dallas Bed Rest Study (1966)

• 5 healthy 20-year-old men

• 3 weeks at complete bed rest with no weight bearing allowed

  • At the time, standard patient care protocol after heart attack

• "Thus, 3 weeks of bed rest at age 20 years reduced cardiovascular capacity more than 30 years of aging."

• Altered the way heart attack patients cared for

  • Encouraging movement and cardiac rehabilitation programs

• What is Cell Signaling: _____________________

• Receptors throughout the body detect changes and respond to ________ ________

• Utilized to monitor and communicate conditions that are regulated through ________ _______

  • (Positive/Negative) feedback is the most common

  • Few instances of normal (Positive/Negative) feedback in human function

• What is Cell Signaling: The processes by which cells communicate with each other

• Receptors throughout the body detect changes and respond to maintain homeostasis

• Utilized to monitor and communicate conditions that are regulated through feedback loops

  • Negative feedback is the most common

  • Few instances of normal positive feedback in human function

Cellular messaging system

• Cells respond to changes in the environment

  • Cells may respond to a ________ stimuli that increases other ________ in their membrane

  • ________ signals the cell to position glucose transport channels into its membrane

• Cell to Cell Communication

  • Direct Communication: _______________________

  • Contact Dependent: _________________________

  • Contact Independent: _________________________

Cellular messaging system

• Cells respond to changes in the environment

  • Cells may respond to a chemical stimuli that increases other proteins in their membrane

  • Insulin signals the cell to position glucose transport channels into its membrane

• Cell to Cell Communication

  • Direct Communication: Signals pass from the cytosol of one cell to an adjacent cell

  • Contact Dependent: Membrane bound signaling molecules

  • Contact Independent: Messenger molecule is released to communicate

Contact Independent Cell Signaling

• Autocrine: _________________________________________

  • Auto- = ______ / -crine = ______

  • Example: ___________________________________________

• Paracrine: ________________________________________

  • Para- = ____________

  • Example: _____________________________________

• Endocrine: ____________________________________________

  • Endo = _______

• Neurotransmitter: ________________________________________

Contact Independent Cell Signaling

• Autocrine: An autocrine messenger stimulates the cell that originally secreted the signal

  • Auto- = self / -crine = secrete

  • Example: Immune System Function (white blood cells stimulate their own replication)

• Paracrine: Chemical messengers that act on cells in the local environment

  • Para- = beside/adjacent

  • Example: Histamine during allergic reactions; protective response against viruses

• Endocrine: Chemical messengers released by glands that utilize the blood to travel to target cells

  • Endo = internal/within

• Neurotransmitter: Chemical messengers secreted by neurons to adjacent cells

Steps in Cell Signaling (Overview)

1. _____________/______________

2. ______________

3. ______________

Steps in Cell Signaling (Overview)

1. Signal Reception/Receptor Activation

2. Signal Transduction

3. Cell Response

Membrane Receptors (extra/intra-cellular)

• Receptors on the cell membrane bind signaling molecule (______)

• Receptor produce their own signal (i.e. produce a second signal)

  • This signal is called a _______________

• Common receptors include:

  • ___________________

  • ___________________

Membrane Receptors (extracellular)

• Receptors on the cell membrane bind signaling molecule (ligand)

• Receptor produce their own signal (i.e. produce a second signal)

  • This signal is called a secondary messenger

• Common receptors include:

  • G-protein Coupled Receptors

  • Receptor Tyrosine Kinases (RTKs)

Intracellular Receptors

• Similar role to membrane receptor, just ____________

• Some chemical messenger can cross through the __________

  • (Don’t need/Need) bind to a membrane receptor

  • Very (large/small) molecules

  • Or (hydrophobic/hydrophilic) messengers

Intracellular Receptors

• Similar role to membrane receptor, just inside the cell

• Some chemical messenger can cross through the membrane

  • Do not need bind to a membrane receptor

  • Very small molecules

  • Or hydrophobic messengers

What determines if a signaling messenger binds to an extracellular receptor vs. an intracellular one?

• Chemistry! (______________ and ______________)

• ______ hormones, like _______, bind extracellular receptors

  • Because they are (hydrophobic/hydrophilic)

  • They (can/cannot) diffuse through the lipid bi-layer

• ______ hormones, like _______, bind intracellular receptors

  • Because they are (hydrophobic/hydrophilic)

  • They (can/cannot) diffuse through the lipid bi-layer

What determines if a signaling messenger binds to an extracellular receptor vs. an intracellular one?

• Chemistry! (lipid solubility and membrane permeability)

• Peptide hormones, like insulin, bind extracellular receptors

  • Because they are hydrophilic

  • They cannot diffuse through the lipid bi-layer

• Steroid hormones, like cortisol, bind intracellular receptors

  • Because they are hydrophobic

  • They can diffuse through the lipid bi-layer

________ _________ – Adding phosphates

• Often (simple/multistep) processes

• Need to (transmit/amplify) signal

• Common steps involve adding/removing a phosphate group to a ________

  • ______________/_______________

• Phosphorylation cascades: ____________________________

Signal Transduction – Adding phosphates

• Often multistep processes

• Need to amplify signal

• Common steps involve adding/removing a phosphate group to a protein

  • Phosphorylation/dephosphorylation

• Phosphorylation cascades: chain reaction of kinases phosphorylating other kinases

• Kinases and Phosphatases: Enzymes that add or remove ___________

  • (Kinase/Phosphatase) adds

  • (Kinase/Phosphatase) removes

• These enzymes commonly activated during ___________________

• Either can activate/deactivate

  • Depends on ___________________

• Common for phosphorylation to "turn (on/off)"

• Modifying an already made protein is called ________________________

• Kinases and Phosphatases: Enzymes that add or remove phosphate groups

  • Kinase adds

  • Phosphatase removes

• These enzymes commonly activated during cell signaling/transduction

• Either can activate/deactivate

  • Depends on the protein they are modifying

• Common for phosphorylation to "turn on"

• Modifying an already made protein is called post-translational modification (PTM)

Signal Transduction - Secondary Messengers

• Second messengers: _____________________

• Cyclic AMP (cAMP)

  • Adenylyl Cyclase: enzyme catalyzes ATP -> _____

• Calcium (Ca2+)

Signal Transduction - Secondary Messengers

• Second messengers: small molecules or ions that relay signals

• Cyclic AMP (cAMP)

  • Adenylyl Cyclase: enzyme catalyzes ATP -> cAMP

• Calcium (Ca2+)

• G Protein Coupled Receptors: ____________________________

  • _______ __________ binding protein

• G Protein w/ GDP = (OFF/ON)

• G Protein w/GTP = (OFF/ON)

  • Example: G protein can activate _______ ________ to produce cAMP

• G Protein Coupled Receptors: Membrane bound receptor protein that binds a "G protein"

  • Guanine nucleotide binding protein

• G Protein w/ GDP = OFF

• G Protein w/GTP = ON

  • Example: G protein can activate Adenylyl Cyclase to produce cAMP

Cell Response (fast and slow)

• Cell response varies by ________ type and ________ type

• Many pathways lead to the activation of ____________________

• May involve the alteration of (intra/inter-cellular) structural proteins (fast/slow)

  • ________ changes if movement is related to response

• May affect the function of transcription factors (fast/slow)

  • Changes the expression of ________

  • Commonly seen in (intra/inter-cellular) receptor pathways

Cell Response (fast and slow)

• Cell response varies by cell type and signal type

• Many pathways lead to the activation of one or more enzymes

• May involve the alteration of intracellular structural proteins (fast)

  • Actin changes if movement is related to response

• May affect the function of transcription factors (slow)

  • Changes the expression of genes

  • Commonly seen in intracellular receptor pathways

3 Steps in Cell Signaling (Details)

• Receptor Activation: ____________________________

• Signal Transduction: ____________________________

• Cellular Response

  • Cell response varies by ________ type and ________ type

  • Many pathways lead to the activation of ____________________

  • May involve the alteration of (intra/inter-cellular) structural proteins (fast/slow)

    • ________ changes if movement is related to response

  • May affect the function of transcription factors (fast/slow)

    • Changes the expression of ________

    • Commonly seen in (intra/inter-cellular) receptor pathways

3 Steps in Cell Signaling (Details)

• Receptor Activation: Signaling molecule binds to the receptor on the target cell causing a conformational change in the receptor to activate function

• Signal Transduction: Initial signal is converted to a different signal inside the cell; this is carried out through proteins that form a signal transduction pathway

• Cellular Response

  • Cell response varies by cell type and signal type

  • Many pathways lead to the activation of one or more enzymes

  • May involve the alteration of intracellular structural proteins (fast)

    • Actin changes if movement is related to response

  • May affect the function of transcription factors (slow)

    • Changes the expression of genes

    • Commonly seen in intracellular receptor pathways