HBIO 250 Midterm 1

Is the covalent bond strength between the 2 terminal phosphates in ATP particularly strong? If not, what properties of ATP have led to its universal usage as "energy currency" in biology?

"It's called a high energy bond because it's a weak bond and relatively easy to break." So the phosphates have high energy and are easy to break down and use for energy.

What is human performance?

"Mechanical resistance and distance per unit time" includes human, task and environmental factors, all interrelated.

Be able to list the physiological changes that take place that poise us to be able to respond to a "stressful" situation.

-Alarm reaction: initial response; increase in cardiac output and blood flow to muscles in response to running -Resistance development: training response; increased cardiac capacity and greater capillary density in the muscles -Exhaustion: When stress is too great, overtraining. Body breaks down

LIMITS TO HUMAN PERFORMANCE

2

HISTORY OF DOPING AND OVERSIGHT

3

SKELETAL MUSCLE ARCHITECTURE AND ULTRASTRUCTURE

5

TERMS

6

Would high altitude have more of an effect on a 100 m dash or a marathon? Why?

A marathon because less oxygen is available to the runners.

Noncompetitive inhibitor

A substance (drug) that reduces the activity of an enzyme (blocks agonist) by binding to a location remote from the active site, changing its conformation so that it no longer binds to the substrate. (allosteric mechanism) -graph changes vertically

During WWII, what drug did the Nazis (including Hitler) and the allied forces routinely take to "stay alert and awake"?

Amphetamine/Methamphetamine

What is the definition of an ergogenic aid or factor?

An aid that increases the potential for work output and thus, human performance

Hypertrophy

An increase and growth of muscle cells. -refers to an increase in muscular size achieved through exercise

What explains aspirin's effects on the stomach and its use as a "blood thinner" at low dosages?

Aspirin is a negative inhibitor of COX1 and COX2 so it inhibits oxygen → it then prevents platelet aggregation so it is less likely to have blood clots

During the late 1980s, many of the world records for women's strength events (e.g., discus, shot put, powerlifting, etc.) were set and have been held to this day. What is a logical explanation for this when many other records for swimming and running continue to be set to this day?

At that time (during the late 1980s), things like taking testosterone and other masculine performance enhancing substances weren't yet banned.

What advantages and disadvantages are associated with competing at high altitude?

Affects performance in terms of both gravity and hypobaria -Gravity: long jump, high jump, pole vaulting (but the gravitational pull is affected more by latitude than altitude) -Hypobaric Conditions: Lower O2 availability at altitude has a definitive effect on human performance. Lower air pressure equates to less air and lower drag for many track and field events

Which NSAIDs are specific to COX2 and which are not (i.e., inhibit both COX1 and COX2)?

Celebrex® for rheumatoid arthritis and other autoimmune inflammatory diseases

Why are skeletal muscles multinucleated?

Cells are multinucleated as a result of the fusion of 100's of myoblasts (myo = muscle) that fuse to form each long muscle fiber.

What are the four different ways that a drug can be named?

Chemical name, generic name (international nonproprietary name), proprietary name (manufacturer's name; brand name), mechanism of action -the chemical and generic names NEVER change

Competitive inhibitor

Competes with an agonist at binding site -A substance that reduces the activity of an enzyme by entering the active site in place of the substrate whose structure it mimics. -graph changes horizontally

EC50

Concentration of a drug required to produce 50% the desired or maximum response

Agonist

Drug or substance that inactivates a receptor

Antagonist

Drug that acts against and blocks an action. (prevents agonists from binding...bc it binds but does not activate receptors)

Pharmacological Aids

Increase physical power, mental strength, or mechanical edge by influencing physiological or psychological processes (e.g., anabolic steroids) -Allowed: Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) (inhibit COX enzymes and reduce prostaglandins thereby reducing inflammation), Caffeine (central nervous system stimulant) -Disallowed: Amphetamines (central nervous system stimulant increase blood pressure, heart rate and blood flow to the active muscles), Androgenic Anabolic Steroids (AASs) (increase muscle mass)

Mechanical Aids

Increases energy efficiency -Allowed: Nike light weight racing shoes -Disallowed: Full-body swimsuits [banned after 200 records fell in 2009])

Psychological Aids

Increases mental strength -Allowed: Hypnosis, relaxation yoga, and music, etc. -Disallowed: Not surprisingly, none of these techniques have ever been banned from sports.

What is meant by an "off-target effect" of a drug?

When a drug has another application outside of its intended therapeutic usage.

What events would be most affected by altitude?

Long distance running

What function do multiple nuclei serve?

Nuclei of each myoblast retained to provide enough mRNA for protein synthesis in large fiber

Nutritional Aids

Nutritional Aids: Increase physical power, mental strength, or mechanical edge by influencing physiological or psychological processes (e.g., protein supplements, creatine, etc.) -Allowed: Creatine Monohydrate (some scientific evidence suggests that short term creatine use can increase maximum power and performance in high-intensity anaerobic repetitive work (jump squats)), Betahydroxybetamethylbutyrate (HMB) (a metabolite of leucine that is purported to influence strength and lean body mass by acting as an anti-catabolic agent) -Disallowed: Any supplement that contains substances that are mimetics for human growth factors or hormones, anabolic steroids, etc.

What nation had more than 25% of its athletes denied from competing in the Rio Summer Olympics for doping?

Russia

Under what moniker did athletes from this same country compete in the "2020" Tokyo Olympics?

Russian Olympic Committee (ROC) but using same colors as Russia

Which schedule (class) of drug is most addictive (I - V)?

Schedule 1 drugs are the most addictive --ex. heroin, methylenedioxymethamphetamine (ecstasy), Lysergic acid diethyl-amide (LSD)

What dictates a drug's potency?

The drug with the lowest EC50 (effective concentration to reach 50% of maximal effect) has the highest potency (i.e., the biggest effect at the smallest concentration)

Following WWII, the allied forces preferred drug was used in sporting events, resulting in what horrific consequences.

They collapsed and ended up dying. Adverse effects include seizures, heart problems, and psychosis

What is the origin of the word "dop"?

comes from Dutch word "dop" which was the name of an alcoholic/hallucinogenic beverages that zulu warriors took before battle to make them more aggressive

Hyperplasia

increase in number of cells

Pharmacodynamics

what drugs do to the body

Pharmacokinetics

what the body does to the drug

According to WADA what substances are prohibited in competition?

-S.6 Stimulants -S.7 Narcotics -S.8 Cannabinoids -S.9 Glucocorticosteroids

What are the different ways in which a drug can have an effect in our body (to what must it bind to have an effect)? -Be able to name all the different ways.

-Acid / base properties (e.g., antacids) -Astringents: contract, "shrink", or dry tissues (e.g., acne medications) -Membrane surfactants: forms pores in cell membranes (e.g., antifungals, antibiotics) -Receptor-site binding (many drugs work this way)

Sarcolemma

-"the sarcolemma functions as a barrier between the extracellular and intercellular parts of the muscle fiber cells." -Refers to the plasmalemma + basement membrane [extracellular]

The connective tissue sheaths that include the epimysium, perimysium and endomysium help to organize skeletal muscles. What structural units do they form, what are they composed of, and what structures do they come together to form at the end of skeletal muscles?

-1. Epimysium: covers the muscle (exterior collagen layer) and separates it from other tissues --Composed of collagen, elastin & EC matrix -2. Perimysium: bundles muscle fibers into groups called fascicles and covers a fascicle --Composed of collagen and elastin & EC matrix -3. Endomysium: conduit for capillaries, nerve fibers and myosatellite cells, surrounds individual muscle fibers --Composed of composed of collagen, elastin and EC matrix

Muscles that have relatively short fiber length (FL) to muscle length (ML) are designed for force generation or velocity and high tendon displacement or excursion [joint rotation]?

-> When you have a muscle w. FL < ML it is designed for force generation -> When you have a muscle with FL = ML, it is designed for high velocity and high tendon displacement or excursion [joint rotation]

What series of hormonal events happen during the "fight or flight response"?

-Amygdala initiates "fear" response: -Hypothalamus releases CRH -Pituitary releases ACTH -***Adrenal gland releases cortisol & epinephrine. -Behavioral responses include alertness, focus, reduction of pain receptors -Cortisol and epinephrine increases blood pressure & blood sugar, redirects blood flow to the heart, muscles and brain

In regard to NSAIDs, what two pathways may these drugs affect?

-COX-1: cytoprotective prostaglandins (stomach lining / platelet aggregation) -(constitually expressed → expressed at all times): cytoprotective prostaglandins (stomach lining/platelet aggregation), take alongside food (Cytoprotective for gut lining) -COX-2: inflammatory prostaglandins -pro-inflammatory → recruit inflammatory white cells sensitive skin pain receptors → stimulate hypothalamic fever response (anti inflammatory) -NSAIDs block COX receptors

How can epinephrine/ norepinephrine have opposite effects in different tissues (think receptor types)?

-Drugs often work on more than one receptor, and as a result produce more than one kind of biological response --Ex: norepinephrine (a sympathetic neurotransmitter) relaxes bronchial smooth muscle via β2 adrenergic receptors but constricts arterial smooth muscle of blood vessels to digestive tract and kidneys via α1 adrenergic --------results from NE binding to different adrenergic receptor subtypes (α and β) at different anatomical locations

What is EC50?

-EC50 can be defined as the concentration required to obtain a 50% [...] effect -Refers to the concentration of a drug, antibody or toxicant which induces a response halfway between the baseline and maximum after a specified exposure time.

Know the different routes for the absorption of drugs. What are the advantages/disadvantages/ challenges of each?

-Enteral = Oral (sublingual, buccal, & via other mucous membranes [e.g., rectal, vaginal]): most common route of drug administration ---------The gastrointestinal (GI) tract provides a significant barrier to drug administration - highly acidic, thick cell layers, many digestive enzymes, etc. ---------Factors affecting absorption: Stomach acidity (pH), GI motility, Physio-chemical reaction with the contents of the gut (other drugs, enzymes, etc.), Fat solubility of the drug (is it oil-based [lipophilic] or water-based [hydrophilic]?) -"Parenteral" (outside of the intestines) -Injectable: (ID) - slowest uptake, e.g., allergy or TB test : bc oral is the slowest for faster response or for a drug susceptible to breakdown in the GI tract, an injectable route is preferred -Intravenous (IV) - fastest, e.g., overdose reversal -"SubQ" or subcutaneous - faster than IM, e.g., insulin, some vaccinations -Intramuscular (IM) - quick, e.g., vaccines -Topical (any mucous membrane including lungs, eyes, nose ears, transdermal): Most topical administrations are NOT absorbed into the body as much as other types of administrations -- Advantage = can have a localized effect. Some are designed to be taken over hours-days. -Aerosol: (inhalant)

Costameres

-Four different cytoskeletal networks form the costameres, which are periodic membrane-associated plaques that codistribute with Z-lines and M-lines, connecting the sarcomeres to the plasmalemma a) Cadherin-based linkages to actin and desmin (cardiac only) b) Integrin-based focal adhesions c) Dystroglycan complex (DGC) and d) Spectrin-based membrane cytoskeleton -Transduce contractile force from the Z-line to the basement membrane (laterally), ultimately to the endomysium → Couple the force-generating sarcomeres with the sarcolemma of striated muscle (both skeletal and cardiac) -clusters of structural and regulatory proteins that link the Z-disks of the outermost myofibrils to the sarcolemma and extracellular matrix

Microanatomy of Sarcomere

-I (Isotropic) band - Thin filaments only (actin) -H (Helles) zone - Thick filaments only (myosin) -A (Anisotropic) band - Thick filament including overlap with thin filaments -M (Mittel) line - Proteins in the middle of sarcomeres where thick filaments attach -Z (Zwischen) disk - Proteins at the ends of sarcomeres where thin filaments attach. Two Z-discs per sarcomere (each shared with adjoining sarcomere)

Cytoskeleton

-In addition to giving muscle fibers shape and holding intracellular structures in place, the cytoskeleton is very important in reinforcing the plasmalemma during contraction (like an internal frame of a tent). - Actin, spectrin and dystrophin important in this function -Striated muscle contains specialized membrane linkages known as costameres that anchor Z-lines (and M-lines) to the membrane -A network of fibers that holds the cell together, helps the cell to keep its shape, and aids in movement

By which routes are drugs "detoxified" and eliminated from our bodies?

-Kidneys (urine) -Salivary glands (saliva) -Sweat glands (sweat) -Pulmonary epithelium (exhaled gases) -Mammary glands (milk) -Gastrointestinal tract (feces)

What are four different reasons why an athlete may take a drug?

-Legitimate therapeutic use (prescription drug), -Performance continuation (treatment of an injury), -Recreational / Social use (legal and illegal), -Performance enhancement

BASIC PHARMACOLOGY

4

According to WADA what methods are prohibited?

-M.1 Manipulation of blood and blood components -M.2 Chemical and physical manipulation -M.3 Gene doping

What is the relationship between metabolic performance and both relative anaerobic and aerobic power (see slide #28)?

-Metabolic performance and relative aerobic power have a positive exponential relationship -Metabolic performance and relative anaerobic power have a negative exponential relationship

Sarcomere Mechanism of muscle contraction

-Muscle relaxed: sarcomere shortens with contraction -Muscle contracted: H zone and I band both shorten, while A band remains constant

According to WADA what substance is allowed in certain "sports" like darts but prohibited in most others?

-P.1 Beta blockers -(Alcohol was eliminated this past year)

Be familiar with the different types of skeletal muscle fiber arrangements: parallel (fusiform, parallel interrupted, & convergent) vs. pennate (uni-, bi-, multi-). Be familiar with the functional consequences of sarcomeres arranged in series and parallel as well as the angle of pennation (pinnation).

-Parallel Fiber Arrangement: -----Fusiform • Parallel Interrupted (rectus abdominus) • Convergent -Pennate Fiber Arrangement: allow for a greater number of fibers to attach to the tendon, effectively increasing the cross-sectional area -----Increase cross-sectional area = increased force production -----Angle of pinnation decreases tendon/muscle force relative to fiber force -----Unipennate • Bipennate • Multipennate

According to WADA what substances are prohibited at all times?

-S.0 Any pharmacological substance not approved for human therapeutic use -S.1 Anabolic agents -S.2 Peptide hormones, growth factors, and related substances -S.3 Beta-2 agonists (bronchodilators) -S.4 Hormone and metabolic modulators -S.5 Diuretics and masking agents

Know what the WADA consequences are on slide #16 and when it is permissible to use some of the substances banned.

-Prohibited substance or method: 1st offense - mandatory 2 year suspension ; 2nd - life unless exceptional circumstances apply -Exceptional circumstances provide for the sanction to be waived if no fault or no significant fault can be established -Inadvertent doping: 1st - warning of up to1 year; 2nd - 2 years; 3rd - Life -Refusing or failing to sample collection/evasion/tampering: 1st - 2 years; 2nd - life -It is only permissible to use if athlete is given a Therapeutic Use Exemption: "Permission to use, for therapeutic purposes, drugs which are otherwise prohibited in sporting competition" (mandatory)

The components of a sarcomere including all the major proteins of the thin and thick filaments (actin and myosin, respectively)?

-Sarcomeres are constructed of a relatively small number of specialized proteins -----The two most characteristic proteins (directly responsible for the contraction) are myosin and actin, arranged thick and thin filaments respectively -Thin Filaments: made of two intertwined F-actin filaments → Each filament is constructed from many actin monomers (G-actin) → Each G-actin contains a single binding site for myosin → A large protein (nebulin) spans the length of the thin filament and attaches it to the Z-disk -Thick filaments: made of ~250 myosin molecules with 'heads' at the end of each filament → Each myosin head has one G-actin binding site and one binding site for ATP → Titin is a gigantic protein that spans the entire sarcomere and connects the thick filaments to the Z-disks

Be familiar with the former and current rulings in regard to maximum allowable testosterone levels for female athletes to compete and the specific case of Caster Semenya?

-Semenya is a South African female that has 46,XY DSD, high testosterone levels, and dominates in the middle running events such as the 400, 800 & 1500 m. -(IAAF), now the World Athletics, ordered a sex determination test, and it was leaked that she is an XY intersex individual. -She was not allowed to compete in some competitions but did compete in the 2012 Olympics where she won silver in the Rio 2016 Olympics, where she won gold in the 800 m -When asked to artificially lower her testosterone levels she said, "Why will I take drugs? I'm a pure athlete. I don't cheat. They should focus on doping, not us." -Max test levels for females: five nanomoles per liter

Elimination (of substance from the body)

-The liver is the primary organ responsible for breaking down drugs into inactive compounds that can be excreted from the body -Drug metabolism occurs via enzymes. Groups of enzymes transform (i.e., metabolize) drugs: 1. Converting an active drug into an inactive compound 2. Converting an active drug into another active compound (can have the same action as the original drug) 3. An active drug can be changed into a toxic metabolite 4. An inactive drug can be changed into an active metabolite. -Metabolism for a fat-soluble drug may simply mean converting it into a water-soluble metabolite -There are many routes

In which connective layer do you find myosatellites? What is their function and from where did they come?

-They are found in the endomysium -Myosatellite cells are capable of division and fusion to existing fibers for repair and growth but cannot generate new fibers de novo

What unique morphometrics make Michael Phelps predisposed to be an excellent swimmer?

-Torso is that of a 6'8″ person, enabling an advantageous reach. -Lower body is that of a person 5'10", lowering resistance. -Size 14 feet (and large palm SA) act like flippers; PLUS extended ROM of ankles act like flippers.

What other environmental conditions can affect an athlete's performance?

-Wind: runners encountering a head wind and concludes that on an oval course, while the tail wind helps it is not enough to overcome the head wind and, thus, times are slower -Temperature: Cool temperatures are not rlly problematic, but high temperatures have a definitive effect and can lead to heat exhaustion and heat stroke -Humidity: Low humidity can lead to dehydration whereas high humidity, (esp w/ high temps), can lead to difficulties with sweat-induced evaporative cooling -Wind speed and course conditions: problem in downhill skiing -Environmental toxins (air pollution): should more or less equally affect competitors -Water quality and conditions: problem at 2016 Rio Olympics

WHAT IS A PERFORMANCE ENHANCING DRUG & ERGOGENIC AID?

1

What are the functions of the endomysium?

1) Envelopes each muscle cell → 2) Composed of collagen, elastin & EC matrix → 3) Scaffold for developing and regenerating muscle → 4) Conduit for nerves and blood vessels → 5) Connects w/ plasmalemma → 6) Force transduction -separates individual muscle fibers provides the extracellular chemical environment for each muscle fiber creates room for capillaries and nerve fibers to reach every muscle fiber

Hypotrophy

A degeneration of an organ or tissue caused by a loss of cells

Physiological Aids

Augment physiological processes to increase power -Allowed: Oxygen (usage, before or after certain events (not during)), Massage (for releasing muscle tension and restoring balance to the musculoskeletal system) -Disallowed: blood doping (- infusing RBCs into the body to increases O2 carrying capacity), Erythropoietin (EPO) (hormone that stimulates red blood cell production)

Might Schedule 1 drugs have a therapeutic use that has not yet been recognized by the FDA? What about the other schedules?

Everything but schedule 1 might have a therapeutic use as recognized by the FDA

What unique morphometrics or genetics make Usain Bolt predisposed to be an excellent sprinter?

He is tall, 6'5" (1.83 m), allowing for longer strides meaning fewer steps (41 as compared to 43 - 50 on average) Has proportionally longer toes thus applying force for, longer period (0.1 s foot contact at max velocity) Has proportionally shorter shanks (faster strides) Has the functional ACTN3 gene (common for many elite sprinters and 75% of Jamaicans), encoding the alpha actinin 3 isoform, which is only expressed in fast-twitch muscle

Is the chewing of khat and coca leaves allowed by WADA? Why or why not (i.e., what would they be classified as)?

No, it is not allowed by WADA because khat leaves contain cathinone. Khat was proven to produce the same effects of performance enhancement which lead to the banning of amphetamine. Coca leaves (cocaine) are obviously not permitted either. Both are classified as S.6 drugs: prohibited substances in competition

Do schedule I drugs have FDA-recognized therapeutic use?

No, they have no currently accepted medical use

Be familiar with unique properties of the plasmalemma, e.g., 50% cholesterol (why?), convolutions at motor end plate, 77.5% reduction in surface area during maximum contraction

Similar to other plasma membranes with some notable exceptions: -At the motor end plate, it is highly convoluted due to junctional folds -Elsewhere, there are small folds when at rest or contracted -When fibers are fully contracted, surface area can decrease by as much as 77.5% -About 50% of the membrane is cholesterol (range observed in all cells: 7 - 55%); cholesterol greatly stiffens the plasmalemma at this concentration -Integral membrane proteins include: a. a number of different hormone receptors, b. integrins: proteins that link the basement membrane to the plasmalemma and cytoskeleton and have important signaling functions

How does low-dose strychnine enhance a runner's performance (be specific)?

Strychnine is an antagonist of inhibitory glycine receptors in motor neurons. Causes the motor neurons to become "hyperexcitable" (lower threshold to excite them [blocks chloride channels thereby raising resting membrane potential])

Efficacy

The ability of a drug to produce the desired or maximum response

Potency

The amount of a drug required to produce the desired or maximum response

What is the plasmalemma?

The name for plasma membrane in muscles -This is the plasma membrane that surrounds each individual muscle fiber. This membrane is part of a larger unit referred to as the sarcolemma.

Affinity

The speed to which a drug binds to a receptor or protein

Does training increase the VO2max? If so, by what mechanism(s)?

VO2max CAN be increased substantially with training through cardiovascular conditioning

What is a drug?

a substance that has a physiological effect when introduced into the body -Textbook: Drugs are chemical substances that, by interaction with biological targets, can alter the biochemical systems of the body. -In pharmacy, a drug, also called a medication or medicine, is a chemical substance used to treat, cure, prevent, or diagnose a disease or to promote well-being.

Affinity

the speed/strength at/to which the drug binds to the receptor

Efficacy

the strength of the physiological response caused by the drug binding to the receptor