Prelim 3 Biog1440 Flashcards
Symbiosis
The living together between organisms
-Interactions and possible co-evolution with associates microbes that allows some biological exchanges
Mutualism
Ex. bees and flowers
Species A, benefits
Species B, benefits
Commensalism
Ex. barnacles sticking and feeding out of whales
Species A, benefits
Species B, neutral
Parasitism
Ex. parasites
Species A, benefits
Species B, costs
Endosymbionts
microbes that reside within the body or cells of an organism
ex. wolbachia is a reproductive aprastie of insects and nematodes
ex. mitochondria and chloroplast
Lynn Margulis endosymbiosis theory
The eukaryotic cell could arise from a symbiotic union of primitive prokaryotic cells. This states that you start with two microbes and they engage in such a tight symbiosis that it leads to a eukaryotic cell.
Symbiogenesis
Mitochondria and chloroplasts evolved from certain bacteria engulfed by primitive cells
Microbiota
The ecological community of microorganisms associated with a host
ex. the skin microbiota
- The gut microbiota is not endosymbiotic, because the gut lumen is not “inside the body”
Rhizobacteria
They occupy the rhizosphere. Could either:
- Stay on the surface of the root.
- They are endophytic. They live between the cells of host plant tissues and form root nodules
Rhizobacteria depend on…
Nutrients secreted by plant cells, in return, they help to enhance plant growth by
- Producing chemicals (or some nutrients) that stimulate plant growth
- Producing antibiotics that eliminate bad microbes and protect the plant from disease/infection
- Absorbing toxic metals or increasing nutrient availability
The nitrogen cycle
Transforms nitrogen gas into nitrogen containing compounds that can be uptaken by the roots of the plants
- Nitrifying bacteria generate NO3- from NH4+
- The nitrifying bacteria takes the ammonium and generates nitrate. Nitrate will be the favored form of nitrogen that will be absorbed by the root alongside some ammonia.
Nitrogen fixing bacteria
Use nitrogen and generate ammonia (NH3) that will become ammonium (NH4+)
Ammonifying bacteria
Some additional bacteria can also generate some ammonium from a different source. They use decomposition products from the soil and generate some ammonium
Denitrifying bacteria
Takes nitrate and actually generates nitrogen (N2). So they do not help with the growth of the plant but would oppose it.
Rhizobia
Endosymbionts of legumes. Along a legume’s roots are swellings called nodules, composed of plant cells colonized
Nodules
Root tissue but mostly filled with some of the Rhizobia bacteria
Relationship between rhizobia and plants
The plant obains fixed nitrogen from Rhizobium, and Rhizobium obtains sugar and anaerobic environment
Development of nitrogen-fixing root nodules
Chemical dialogue between root cells (flavonoids) and Rhizobia (Nod factors)
To initiate the dialogue once a plant wants or needs to engage in symbiosis with Rhizobia, it will secrete some compounds called flavanoids (which are pigments) and those pigments will be synthesized and diffuse in the ground. If there is Rhizobia in the ground, they will bind and recognize the flavanoids. In response, they will produce proteins, NOD factors, that diffuse back towards the root. When the root receives some of those bacterial derived NOD factors, the roots will modulate the activity, their shape, and somehow follow the trail of the NOD factor a finds a microbe to internalize it
Where does Rhizobia attach?
The root hair which causes them to deform, grow, find and attach to microbes so it will enter those threads and colonize the roots. They grow within the root to develop these nodules.
Microbes in the human microbiota include species from each major domain:
- Bacteria ex. proteobacteria, cyanobacteria
- Archaea ex. crenarchaeota “extremophile”
- Eukarya ex. Fungi, yeast, plants, animals
Microbiota cannot be
Cultured
New solutions to microbiota investigation
Next generation sequencing: does NOT require culturing
Metagenomics: sequence-based analysis of genome of entire microbial communities, does not require culturing
Principal Component Analysis (PCA) Graph
Regroups together the different type of microbial community that look more alike
Microbiota is most abundant in the
GI tract. The large intestine is the preferred site. Over 70% if all bacteria are in the colon.
GI Microbiota is dominated by 2 phyla
Firmicutes and Bacteriodetes
Bacteria increase in abundance and diversity…
From proximal to distal GI tract
Stomach –> Duodenum –> Jejunum –> Ileum –> Colon
Change in gut microbiota can possible explain…
Disease/infection. This seems like more correlation than causation.
Key functions of the gut microbiota
The gut microbiota is central to intestinal homeostasis and physiology (ability to keep physiological constants steady)
1) Immunity:
- Prevents colonization by pathogens. This means it protects from invading pathogens.
- It educates the immune system (gut, skin, lungs). Without the gut microbes, your immune system would not develop properly. Stabilizes out bar
- Stabilizes gut barrier function (decreases leakage). Prevents gut leakage by making sure the gut epithelium is sealed and nothing from the gut lumen can leak into circulation
2) Metabolic Role:
- Caloric salvage: Ex of B.theta which produces 226 glycoside hydrolases compared to your own 80 glycoside hydrolase. Therefore, these microbes process food and interact with gut digestion and contribute
- Produces short chain fatty acids (SCFAs, colonic fermentation) –> These are food for some cells in your body which are produced by microbiota
- Produces Vitamin K and folate (Vit B) – huge metabolic role
3) Chemical modulator:
- Participates in drug metabolism (activation or catabolism) –> medical drugs can be activated or the catabolism can be regulated by the presence of microbes. Depending on your microbes, the drug may differ from patient to patient
- Deconjugated bile acids (alteration of community –> bile acid malabsorption)
Gut brain axis
The idea that the gut is actually the second most neuron rich organ in the body & its in constant communication with the brain. It’s been proposed that microbes hosted in your gut can use that gut brain axis to influence the function of your brain.
Ways the gut communicates with the brain
- The HPA axis (hormonal axis), means hormones initiated by the brain can influence the gut and therefore, the microbes that they host, On top of that, the brain, through neurons (innervation), can directly influence physiology. (the microbiota is affected by our experiences –> hormonal axis, innervation)
- Microbes in your gut will synthesize neurotransmitters (they also synthesize SCFAs) that can modulate brain cells activity (in turn, microbes send chemical signals, including neurotransmitters, SCFAs, affecting memory, emotions, behavior)
Are our microbiotas the same?
Each individual has their own distinct pattern of microbial. For an individual, their fecal microbiota remains remarkably stable over a person’s lifetime.
-Genetics, diet, immune system affect microbiota
Where do we get our microbiota from?
-Initial exposure occurs during passage through birth canal.
- Then the gut microbiota develops influence by mother and diet (ex. breastfeeding)
- Up to 3 years of age, bacterial abundance and diversity increase (mostly in the first year)
- After that, final bacterial abundance is reached at around 1 years old
Effects of maternal exposures on gut microbiota
- Antisepsis
- Antibiotics
- Diet
- Genetics
- C-section
Dysbiosis
Microbial imbalance of the body
–> if suddenly, the diversity of microbes in your gut changes, generally decreases, and some specific microbes that are normally not abundant become abundant or some that are abundant become non-abundant, this is dysbiosis
O2 Gas
Required for aerobic life, but can also inactivate key enzymes in metabolism; animals rely on O2 carrier proteins (hemoglobin, myoglobin)
O2 is highly reactive (oxidant that accepts electrons)
N2 Gas
Is abundant, but not bioavailable except for a few select organisms that have nitrogenase (a very O2 sensitive enzyme)
CO2 Gas
Enters biomass by photosynthesis and is an important waste product from aerobic respiration
CO2 chemistry in water
Dominated by its reversible hydration to carbonic acid (catalyzed by carbonic anhydrase)
Pasteur Point
(~0.2%) Facultative cells switch from anaerobic to aerobic metabolism
What two things could aerobic organisms do when faced with Low O2 (below Pasteur Point)
- Evolved terminal oxidases with high O2 affinity (bo & bd types
- Turn to more ancient type of metabolism (Fermentation and Alternative electron acceptors)
E.Coli for low O2
- Under most aerobic conditions, the BO type is used, which has a high affinity for oxygen.
- However, if the oxygen levels fall much below the Pastuer point, E.Coli can make alternative types of terminal oxidase (an alternate complex IV) with a significantly higher affinity for molecular O2 and the abolity to bind oxygen even when it’s in the low level (BD-type)
- If oxygen levels fall even further, E.Coli can turn to alternative electron acceptors such as nitrate or fermentation
Efficient mechanisms to bring O2 to tissues
- Oxygen carrier (proteins)
- Human respiration: mitochondrial O2 tension is just above Pasteur Point
O2 Concentration throughout the body
- O2 is highest at the lung (source) but drops dramatically at the mitochondria (sink)
- In the tissues, oxygen is being so rapidly consumed and it can only be brought to the tissues so rapidly by the arterial blood in the capillaries that the steady-state level of oxygen in the tissues is perhaps 20%
Incomplete Reduction of O2 (list the partially reduced species or ROS)
When oxygen is a substrate for reduction to water, partially reduced intermediates can escape
-Superoxide anions
-Hydrogen peroxide
-Hydroxyl radical
These can damage many molecular components, known as oxidative stress
Hydroxyl Radical
When hydrogen peroxide reacts with metals. These reactive species will damage proteins and lipids and contribute to various pathologies
Reactive Oxygen Species (ROS) and Oxidative Damage
Important contributors to many pathologies (often Fe II reacting or other metal cofactors in enzymes)
How do cells protect themselves from ROS?
- Respiratory Shields: The ability of the electron transport chain to efficiently consume oxygen (eukarya have this in the ETC and bacteria have this at the plasma membrane)
- O2 Binding Proteins: Proteins that bind oxygen to allow oxygen sensitive enzymes to function (plants use leghemoglobin to protect O2 sensitive nitrogenase in symbiotic bacteria)
- Detoxification: One important mechanism to protect enzymes against inactivation by ROS is to enzymatically remove these from the cell
- -> superoxide dismutase: removes superoxide, converting it into oxygen and hydrogen peroxide
- -> hydrogen peroxide is removed by catalase and peroxidases
- Avoidance: One strategy is to hide or avoid oxygen by living exclusively in anaerobic environments
Antioxidant enzymes
Superoxide dismutase, catalase, peroxidases. The function of antioxidant is not to remove oxidants entirely, but instead to keep them at an optimum level
Diazotrophs
Organisms that can use N2 gas as a source of nitrogen
Nitrogen fixation is (energy)
Energetically costly! Nitrogenase uses 16 ATP molecules as a source of energy and an input of 8 electrons. It produces 2 ammonia. (NH3)
Microbes can perform this at room temperature
N2+8e- +8H+ —> 2NH3 + H2
nitrogenase
(16 ATP)
Haber Bosch
Nitrogen can be released with a molecular hydrogen to generate ammonia. Requires temp of 400 degrees centigrade and over 400 atmospheres (pressure)
N2+3H2 —> 2NH3
Process for industrial fertilizer production and has been touted as the technological advance that has had the most impact on the modern world, driving the Green Revolution and fueling population growth.
How does nitrogenase assimilate nitrogen gas into ammonia?
Involves a very large complex of proteins, the nitrogenase and these proteins contain a lot of iron molybdenum co-factors, & iron sulfur clusters.
They are involved in the transfer of electrons into the nitrogen
Leghemoglobin
Made by plants to buffer O2 low enough to allow nitrogenase to function, but now so low to stop respiration in plant cells
Hemoglobin
Made by animals to carry O2 through circulation
Myoglobin
Made by animals to store O2 in muscles
Anabaena
Another way in which bacteria can protect their nitrogenase from oxygen is by separating the process of oxygenic photosynthesis from nitrogen fixation
- Heterocyst (specialized N2 fixing cells) only perform respiration and nitrogen fixation (not oxygenic photosynthesis)
- Neighboring cells do oxygenic photosynthesis, thereby making sugars that can feed the heterocyst
Heterocyst
Specialized N2 fixing cells that only perform respiration and nitrogen fixation (not oxygenic photosynthesis). They respire to get energy and fix nitrogen. They share that fixed nitrogen, in the form of ammonia, with the neighboring vegetative cells.
Separation in Time: Crocosphaera Watsonii
This small unicellular cyanobacterium separates nitrogen fixation and carbon fixation in time
-During daylight hours, this organism is a phototroph: uses photosynthesis to fix carbon dioxide into sugars and produces oxygen
- At night, it shuts down its photosynthesis pathways and activates nitrogen fixation (because it isn’t actively producing O2, it isn’t poisoning its own nitrogenase)
A benefit of separating these processes through time is that it allows Crocosphaera Watsonii to share iron which is scarce in surface oceans (iron in enzymes for photosynthesis during the day and actively degrades these large photosynthetic complexes to release that iron and build nitrogenase)
–> energy from sun
Environmental penalties of Haber Bosch
- Consumption of fossil fuels
- Prodigious production of greenhouse gases
- Spoiling of watersheds, by fertilizer run-off (e.g. algal bloom)
Carboxylation: productive
Rubisco catalyzes the carboxylation of ribulose bisphosphate (the initial CO2 incorporation step we consider in the first step of the Calvin Cycle)
Oxygenation: non-productive
Rubsico can also be inhibited by oxygen and it can be an oxidase. But when rubisco acts an an oxidase, there is no net incorporation of carbon into the cell. So this inhibits carbon dioxide production.
Formula for CO2 in aqueous solution
CO2 + H20 –> H2CO3 (carbonic acid) –> H+ + HCO3 (bicarbonate) –> H+ _ CO32- (carbonate)
Carbon-Concentrating Mechanisms
Cells that are performing carbon dioxide fixation through photosynthesis often rely on CCMs. These allow these cells to perform carbon dioxide fixation with much greater efficiency.
- Carbonic Anhydrase (CA)
- Active transport of bicarbonate
- Morphological CCM (cyanobacteria have carboxysomes & algae have pyrenoids)
- Biochemical CCM (capture of CO2 by PEP carboxylase, C4 plants (a spatial mechanism), CAM plants (a temporal mechanism).
Why do we need CCM?
- Rubisco is an unusually slow enzyme with a low affinity for CO2
(even at atmospheric levels of carbon dioxide, rubisco functions at only 35% if its catalytic capacity) - High concentration of O2 competes with CO2
-CO2 solubility in H2O is dominated by chemistry
Carboxysomes
High concentrations of rubisco contained in these symmetrical protein shells
Cyanobacteria concentrate rubisco in these
What occurs in the carboxysomes?
The high concentration of rubisco is coupled with the presence of carbonic anhydrase such that as bicarbonate ion diffuses in, it is rapidly converted into CO2 gas -> CO2 gas is captured by rubisco to be fixed into carbon`
Algae CCM
Rather than encasing their carbonic anhydrase in a protein shell, they use structures called pyrenoids where there is a starch layer that concentrates the carbonic anhydrase and rubisco in these structures
C4 plants
Spatial separation of steps- In C4 plants, carbon fixation occurs in different types of cells (mesophyll & bundle-sheath cells)
C3 plants take carbon dioxide and directly incorporates it into rubisco during the day.
CAM plants
Temporal separation of steps- In CAM plants, carbon fixation & Calvin Cycle occur in the same cell at different times
Solution concentration is determined by
Pressure of each gas (Partial Pressure)
Solubility is determined by
-The gas CO2>>O2>N2 -Temperature -Pressure (Henry's Law) -Salinity
As temperature increases…
Oxygen solubility decreases
As salinity increases…
gas composition decreases (including oxygen)
Gas availability decreases…
With decreasing pressure
Why do we need carrier proteins?
To overcome the limited solubility of oxygen in water. Proteins that contain cofactors (such as the heme group in hemoglobin) that have central metal ions
Hemoglobin uses __ to bind oxygen
Uses iron
Hemocyanin uses __ to bind oxygen
Two copper ions
Hemocyanin
Bind O2 between two copper ions. They float free in the ‘hemolymph”
- Used by mollusks and arthropods
Respiratory physiology of Insects
Insects do not carry oxygen and carbon dioxide through their circulatory system in their hemolymph. I
- Instead, they have a direct exchange of individual body cells through a series of tubes, consisting of a trachea, and branches out into much smaller tracheoles.
- At the end of the tracheoles, there is a fluid filled compartment that allows gas exchange and delivery in these branching tubes to the individual cells
As insects move…
Their air sacs are inflated and contracted which pushes gas in and out of these trachea and tracheal systems
Is the insect respiratory system efficient?
Diffusion is sufficient for smaller organisms. but it does not deliver oxygen and remove CO2 nearly as efficiently as a combined circulatory respiratory system.
The mammalian respiratory system occurs in…
-The exchange of gases in mammals occurs in the alveoli, the terminal sacs at the end of the branches of the lungs
What makes the mammalian respiratory system less efficient? (Dead space)
- The process of inhalation and exhalation creates a mixing of gases, such that the gases that are at the alveoli are already diluted with some of the spent gases from the previous breath
The alveoli
- Terminal sacs at the end of the branched lungs where gases are exchanged. Highly rich in capillaries to allow an efficient exchange of gases and delivery of CO2 from the blood into the lungs for exhalation, and the acquisition of oxygen.
Bulk of CO2 is converted into…
Bicarbonate for transport to the lungs (there is no dedicated CO2 carrier protein). The bulk of CO2 carried from our metabolizing tissues is carried in the blood plasma, largely in its hydrated form as carbonic acid and bicarbonate anion.
CO2 Measurements in the body
- 70% of CO2 is converted to carbonic acid
- 7% of CO2 dissolves in the blood plasma
- 23% binds to hemoglobin (at amino-termini)
Carbonic anhydrase
Converts carbon dioxide into carbonic acid and bicarbonate anion. Carried in the red blood cells
DRAW OUT HOW CO2 DIFFUSES INTO CELL
CO2 released from tissues diffuses passively across the membrane into red blood cells –> converted into carbonic acid, which dissociates releasing protons & bicarbonate anions is exchanged across the red blood cell membrane into the plasma
–> this lowers the pH of our circulating plasma and allows the gas to be carried in its hydrated form back to the lungs
Chloride/bicarbonate anion exchanger (DRAW IT OUT)
The export of carbonate anion from the red blood cells is catalyzed by the chloride/bicarbonate anion exchanger
What is the signal to increase respiration?
The principal signal to increase respiration is when pH becomes too low. As more CO2 is released into the bloodstream, pH levels increase. Major blood vessels detect this and send the message to your medulla. Your medulla causes your ribs and diaphragm to increase depth of ventilation. Then blood pH level will rise and CO2 will decrease
Red Blood Cells
Allows for very high hemoglobin concentrations. Inside the red blood cell are red tetramers at very high concentrations, this is the oxygen carrier protein, hemoglobin
Myoglobin & Hemoglobin curves
- Myoglobin binds oxygen very tightly with a hyperbolic binding curve
- Hemoglobin has a highly cooperative or sigmoidal binding curve where there’s a large change in oxygen bound over a relative small change in oxygen pressure
Myoglobin
A single protein chain surrounding the oxygen carrying heme cofactor, which carries oxygen at this central iron atom
Hemoglobin
A tetramer with cooperative binding
T & R states of Hemoglobin
Hemoglobin exist in the T & R states. This protein undergoes a allosteric transition *changes shape) upon binding oxygen
- Deoxyhemoglobin (T) binds oxygen and that transitions the molecules into the R state
Positive Cooperativity
Refers to the fact that the initial binding of oxygen begins to change the shape of the molecule and enhances the affinity of oxygen to bind
- 2nd O2 binds 3x more tightly than the 1st
- Last (4th) oxygen that can be carried by this tetramer binds 20x more tightly than the first
This means that once oxygen begins to bind, it accelerates the ability of the subsequent oxygen to bind
What can increase the off-loading of oxygen into the tissues?
-2,3 BPG
-H+
-CO2
These weaken the affinity of hemoglobin for oxygen and allow for offload to tissues
How does cell-cell communication influence physiology?
- Regulating cell activity
- Achieved by regulating gene expression and/or protein actvities
Slow: Changing transcription and translation to gene expression, making new proteins
Fast: Modify some proteins to alter their function
Simple cell-cell communication
- Cells can exchange information/chemicals through
cytoplasmic exchange of diffusible chemicals
Cell junctions:
- Receptor/ligand interaction on the cell surface. Requires direct contact between the cells: one cell will have a receptor and one will express a ligand on its surface. The binding of the receptor to the ligand will provoke a change in the cell that has the receptor
Complex cell-cell communicaton
- For long-range regulation, communication is based on the secretion of chemical signals
Fast: neurotransmitters (short range diffusion, but cells project long protrusions=axons)
Very fast transmission of information, which is an action potential that goes through an axon and then you have a very short range diffusion at the synapse to trigger changes in the postsynaptic cell. Achieved through electrical signal
Slow: hormones (signal can achieve long range diffusion) - Released in the circulatory system
- Produced by non-neural endocrine cells
- Produced by neurosecretory cells
Hormones have 3 ranges of action
Short: Autocrine (acts on the same cell)
Middle: Paracrine (acts on neighbors)
Long: Endocrine (requires circulation)
Chemical signals that are secreted and bring regulatory messages to receiving cells
- Hormones
- Neurotransmitters
- Growth factors
- Cytokines
Target cells
Cells that have receptors for specific hormones. Hormones can reach all parts of the body (circulation) so all cells are exposed, but only target cells will respond
Hormones
Allow to exchange information and modulate cell behavior and activity. They often are key signals in feedback loops that comprise more than one cell type
Feedback systems
The product of a process is used to regulate the production of the product
Stimulus
Equivalent to a deviation from normal physiological conditions (ex. having a higher temperature than the set point)
Negative Feedback Loop
Will oppose the initial stimulus (thermoregulation)
Positive Feedback Loop
Will increase the stimulus (pepsin *chain reaction)
Hormones are defined by:
- A source (they come from) specialized secretory cells
- Mode of transport (need to be) released into the circulatory system
- Physiological role: (act as) cellular regulators
- Relative effectiveness: Hormones work at very low concentrations because they are released in circulation so you can image that there is a high dilution factor. Other chemical signals do not have to have this low concentration effect because they are released on site at much lower dilution.
- Concentration is regulated: via rate of synthesis, secretion & degradation. The concentration of the hormone is the message.
Hydrophilic hormones
Water-soluble hormones that are secreted by exocytosis, travel freely in the bloodstream, and bind to cell-surface receptors.
- No trouble getting into circulation
- Challenge: Passing plasma membrane
Receptor hormones must be at cell surface
Lipophilic hormones
Diffuse across cell membranes, travel in the bloodstream bound to transport proteins, and diffuse through the membrane of target cells
- No trouble going into the cell
- Challenge: getting into circulation. They bind to transport proteins
Ex. of lipophilic hormones
- Sex steroids (testosterone, progesterone, oestrogens)
- Glucocorticoids
- Mineralocorticoids
How do lipophilic hormones influence a cell?
Lipid soluble hormones enter the receptor inside the cell. The hormone + receptor can go in the nucleus, influence transcription and therefore gene expression, This makes the cell generate new proteins and thus alter its function
Nuclear receptors
Proteins that act as both a receptor and transcription factor
Binding of the hormone changes the activity of the nuclear receptor and modifies gene expression (it increases or decreases the rate of transcription of target genes)
Ex. of hydrophilic hormones
- Catecholamines (epinephrine)
- Thyroid stimulating hormone
- Human Growth Hormone
Transduction Pathways
- The ligand binds a receptor at the surface
- The receptor has enzymatic function and triggers signaling cascades = transduction pathways
- Involves the synthesis of 2nd messengers of sequential protein modifications (ex. phosphorylation)
Transduction Pathways, ex. 1: a receptor and kinase cascade
- Receptor-kinases often initiate these pathways: Binding of the ligand activates the receptor
- Phosphorylation of an inactive kinase activates its kinase function. This active kinase then phosphorylates and activates a more downstream kinase …
- Cascade effect for all 3 kinase
- After the 3 events of phosphorylation, you end up generating some active protein by phosphorylating them ex. enzymes or cellular responses
Is phosphorylation reversible?
Phosphorylation is often reversible. Enzymes called phosphatases can dephosphorylate proteins and put them back in an inactive state
Transduction Pathways, ex 2: GPCR & cAMP
- G-protein coupled receptors initiate the pathway
- When the receptor binds hormones, the G-protein gets activated and will bind GTP.
- When the G protein binds GTP, it will bind another protein, generally an enzyme, and this enzyme will transduce a signal
- The enzymes transduce the signal by synthesizing some molecules and the concentration of those molecules will be relaying the information inside the cell. These molecules are called secondary messengers (THe first messenger is the hormone)
- The concentration of the second messenger results in the activation of kinases and therefore, cellular responsese
Two enzymes downstream of GPCRs:
- Adenylate Cyclase
- Phospholipase C
Adenylate Cyclase synthesizes…
A second messenger (cAMP or cyclic AMP) –> Protein Kinase A
Uses ATP to build the second messenger, cAMP
The concentration of cAMP in the cell should somehow reflect the activity of adenylyl cyclase and therefore, the amount of hormone initially present
- cAMP leads to the final kinase activation and leads to response enzymes being activated, genes transcribed
Transduction pathways, ex 3: GPCRs & Calcium signaling
- Phospholipase C cleaves PIP2 into IP3 and DAG. IP3 acts as a second messenger.
- IP3 goes at the surface of the ER and opens a calcium channel
- Calcium stored in the ER, now goes into the cytoplasm. Calcium also acts as a second messenger in that transduction pathway.
- Calcium then binds proteins, some being kinase, and that will activate cellular response
Amplification
Transduction pathways are cascades of biochemical events to allow for amplification. Hormones work in low concentrations so there might only be 1 signaling molecule entering. To produce a sufficient cellular response, there needs to be amplification.
Major Plant Hormones
- Auxins
- Cytokinins
- Gibberellins
- Abscisic acid
- Ethylene (aging fruits)
- Brassinosteroids
- Jasmonates
- Strigolactones
Plant hormones that control growth
Auxin, cytokinins, Gibberellin
Plant hormones that antagonize growth
Abscisic acid (hormone inhibitor), Ethylene
Auxin
- Stimulates growth (cell elongation and increased division
- Auxin is produced in shoot tip and transported down the stem. This isn’t passive and is done from cell to cell through specific transport proteins
Phototropism
- Growth in plants results in phototropism, plant growth is sensitive to light.
- Growth direction is “towards the light source”
Mechanism for phototropism
Elongation of cells further from light which generates a curvature and bends the stem towards the light
- Darwin Darwin experiments
- Boysen-Jensen`
Principal of Auxin
Auxin is distributed away from light (so if light comes from one side, it will go on the other side & then move down the stem) –> cells close to the light won’t receive much auxin and cells away will receive more
Auxin away from the light:
- Stimulates proton pumps in membrane and acidify the cell
- Low pH activates expansins, enzymes that loosen the cellulose –> loose cellulose away from the light
- This allows the cells to elongate, swell, and grow, away from light
Apical dominance
The shoot apex inhibits the growth of lateral buds (to prioritize vertical growth)
The effects of Auxin are concentration dependent
First stimulation, then inhibition, The more auxin you will stimulate growth until a point where suddenly, you will inhibit growth
Auxin is a morphogen
(draw the picture)
Geotaxis
Auxin influences geotaxis (different parts of the plant will either go towards or away from gravity Stem --> away from gravity Roots --> towards gravity Shoots --> negative geotropism Roots---> positive geotropism
Endocrine glands
Endocrine cells are often grouped in ductless organs called endocrine glands such as the thyroid & parathyroid glands, testes, and ovaries
Pineal gland
Produces melatonin, regulated circadian rhythm or night and day oscillations of your physiological responses
Hypothalamus (grouped with the pituitary gland)
The master regulators of your endocrine system
- Hypothalamic-anterior pituitary: tropic hormones
- Posterior pituitary: ADH, Oxytocin
Thyroid gland
Located at the basis of the neck and synthesizes & secretes thyroid hormones that are master regulators of your metabolism and also thermoregulation
Adrenal glands
Located on your kidneys. These adrenal glands will also be important in terms of endocrine regulation. They synthesize corticosteroids and also epinephrine or adrenaline. Master regulators of stress response
- Cortex: corticosteroids –> stress, immunity, metabolism
- Medulla epinephrine (adrenaline) –> fight or flight
Pancreas
Secretes insulin and glucagon, 2 extremely important hormones that regulate glucose levels in blood
Ovaries (female) testes (male)
Androgens, Estrogen –> reproduction
The same hormone can have…
Different, even opposite effects on different target cells
- Depends on the receptor for the hormone
- Depends on the transduction pathway activated (which varies by cell type
Explain the liver, skeletal cell receptor example (optional)
Epinephrine effects both the liver and skeletal cells in different ways
Liver: Epinephrine increase blood glucose levels
Skeletal: Blood vessels with epinephrine relaxes the cell which leads to vessel dilation, increasing flow to skeletal muscles. Muscle cells in other blood vessels lead to cell contraction which results in blood vessel constriction, decreasing flow to intestines.
Simple hormonal pathways (endocrine)
Stimulus –> secretion of hormone by endocrine cell –> receptor (in target cells) –> physiological response
Ex. of negative feedback loop
Low pH in the duodenum –> S cells of duodenum –> Secretin –> Pancreatic cells —> Bicarbonate is released
Ex. of positive feedback loop
Suckling –> Oxytocin –> Smooth muscles in mammary glands –> milk release (because milk release leads to more suckling by the baby)
Tropic hormones
Function is to reach other endocrine glands and regulate the secretion of the hormones secreted by these endocrine glands
Difference between tropic and non-tropic hormones
Tropic hormones are hormones that trigger the release of another hormone once they reach an endocrine gland. Non-tropic hormones reach a receptor and initiate a cellular response.
Endocrine axes
Often a 3-step cascade of hormones where the first gland will release a hormone that will go in the second gland that will release a second hormone that will go on a third gland that releases a third hormone that will make physiological change
The Hypothalamus/Pituitary/Thyroid system (HPT)
- Hypothalamus releases TRH, the TRH will stimulate the release by the pituitary gland of TSH, TSH will go into the thyroid gland and stimulate the release of thyroid hormones
The Hypothalamus/Pituitary/Adrenal Cortex Axis (HPA)
- Hypothalamus releases CRH, the CRH will stimulate the release by the anterior pituitary of ACTH, ACTH will go into the adrenal cortex and stimulate the release of CORT
Pituitary gland
Composed of the posterior and anterior pituitary.
Anterior is the real gland, the posterior is just an outgrowth of the hypothalamus.
Posterior or neurohypophysis is just a collection of axonal projections from the hypothalamus-
2 key functions of the hypothalamus:
1- Neurosecretory cells (from hypothalamus) secrete two posterior pituitary hormones (ADH, Oxytocin)
These hormones are stored in the pituitary gland, and released
2- Hypothalamic cells control the endocrine activity of the anterior pituitary gland (adenohypophysis) … i.e. the hypothalamus releases some hormones that act on the anterior pituitary ro then release other hormones
Secretion of ADH or vasopressin in the posterior pituitary
Stimulates reabsorption of water in kidney
Secretion of Oxytocin
Contraction of mammary gland, uterine muscles
(optional) Hormone production in the anterior pituitary is controlled by
Releasing hormones and inhibiting hormones secreted by the hypothalamus
Anterior pituitary releases:
FSH & LH (testes or ovaries), TSH, ACTH, Prolactin, MSH, GH
Hormones produced by the anterior pituitary have two modes of action
Tropic effects- their job is to regulate the activity of distant glands that release specific hormones
Non-tropic hormones- target tissues and modulate physiology
FSH & LH for HPG axis
(tropic effects only) Will go into the testes or ovaries and modulate the secretion of androgens and estrogen by the gonads.
Growth Hormone
Actually a hormone that has both tropic and non-tropic effects
Regulation of organismal metabolism
What is regulated?:
- -> Protein synthesis/cell division/cell growth (anabolic effect)
- -> Energy expenditure/reserve mobilization (catabolic effect)
- -> levels of circulating metabolites (i.e. glucose in blood)
What are the key endocrine axes regulating metabolism
- Growth Hormone (GH) and Insulin-like growth factor (IGF-1)
- -> anabolic in muscles and catabolic in fat - The HPT axis
- -> Thermoregulation and basal metabolism - Insulin and Glucagon
- -> Regulation or circulating sugar
Growth hormone for regulating metabolism
Growth hormone has tropic and non-tropic effects.
-Non-tropic effect: Promotes catabolic changes directly in target cells. Breaks down fats. Increased blood sugar.
-Tropic-effect: stimulates the release by the liver, of growth factors that are called insulin-like growth factors or IGF-1
Growth hormone promotes catabolism in reserve tissues, so you mobilize resources, and then boost growth in the target organs that will use those resources. Combined stimulation of growth and resource mobilization is mostly in adipocytes and liver cells. These cells will break down glycogen, generate some sugar, break down lipids, generate some sugar, and that energy will go in the cell that receives IGF-1, which is stimulated by GH
IGF Negative Feedback Loop
Where the levels of IGF will somehow inhibit different steps that lead to the release of growth hormone. FOr instance, the levels of IGF will inhibit GHRH release and well as GH synthesis
The final products of the HPT axis
T3 and T4. T4 is released as a prohormone by the thyroid gland but it’s not very active so T4 needs to be converted into T3, which is 5x more active to really have an effect.
- Generally T4 is converted into T3 in just target cells
T3
Increases: Basal metabolic rate Protein synthesis, growth Elevates body temperature Stimulates fat mobilization
T3 & T4 Negative Feedback Loop
If you have a lot of T3, you do not release a lot of TRh and TSH and therefore you stop generating T4
Hypothyroidy
Weight gain, lethargy, cold intolerance
- -> thyroid function is sub-optimal. This means lower metabolism which leads to weight gain
- -> could be caused by an imbalance of diet. T3 and T4 require iodine
Grave’s disease (Hyperthyroidy)
The thyroid gland will be more active and more T3 and T4 will be secreted and increase your metabolism way above normal levels
–> high temp, sweating, weight loss, high blood pressure
What do the pancreatic islets produce?
Insulin and glucagon
Insulin
Produced by B-cells in Langherans islets
Storage hormone that tells cells to uptake glucose and build stock and grow.
–> increased protein translation (required for growth)
promotes glycogen synthesis (especially in the liver) –> storing glucose in the form of a polymer, glycogen
–> promotes uptake of sugars by all the target cells (called the hypoglycemic effect)
Insulin causes hypoglycemia
Glucagon
Produced by A-cells of Langherans islets
Regulator of blood sugar produced in the pancreas and with opposing effects to insulin.
More hyperglycemic because it will instruct cells to take some reserves and release glucose in circulation
The Adrenal Glands
- Sit at the top of the kidney
- Each adrenal gland consist of two glands, the adrenal medulla and the adrenal cortex
Adrenal Cortex
Corticosteroids, steroids hormones like glucocorticoids and mineralocorticoids
Adrenal Medulla
Synthesis and release of adrenaline
Cortex has 3 regions involved in the synthesis of specific hormones
Zona Reticularis: Involved in synthesizing precursors of hormones that are the androgens
Zona fasciculata: Responsible for generating glucocorticoids
Zona glomerulosa: (outer layer of the cortex) is the region which is responsible to synthesize mineralocorticoids
Cortex’s response to stress
Hormone: Corticosteroids (glucocorticoids)
Stimulus: Stress
Regulated by: Cortex is stimulated in response to stress by the HPA axis (response initiated in the hypothalamus which triggers pituitary gland activation, which release ACTH. Then ACTh will go into the cortex and stimulate the production of glucocorticoids).
Medulla response to stress
Hormone: Adrenaline (epinephrine), noradrenaline
Stimulus: Stress
Regulated by: Autonomic nervous system
The Autonomic Nervous System
- Is a division of the peripheral nervous system that influences internal organ function of internal organs
- Two divisions in the autonomic nervous system: parasympathetic divisions and sympathetic divisions
Parasympathetic Nervous System
This system, when activated, will push something that we call the “rest and digest” physiological condition. Rely on acetylcholine as a neurotransmitter
- Pushes the constriction of airways
- Slows down heart beat
- Stimulate gut motility
Ultimately, it’s decreasing physical activity, promoting rest, but investing and diverting resource into digestion
Sympathetic divison
Involved in the regulation of what is called the “flight or flight” response. Postganglionic neurons, those terminal neurons, will use norepinephrine. The result of the activation of the sympathetic nervous system will be:
- To relax airways (so more air comes)
- Accelerate heartbeat
- Divert bloodstream towards the muscles
- Decrease gut motility (have less blood towards the digestive tract)
Ultimately, it primes your physiology for action while the parasympathetic system primes your physiology for rest and digestion
Stress and HPA axis
Stress and prolonged activity both trigger the HPA (but it will respond more to something like a prolonged stress)
Brain (stress) –> activation of the hypothalamus –> anterior pituitary –> through circulation
Example of hormone produced by adrenal cortex
Glucocorticoids such as cortisol
A negative feedback loop regulates cortisol levels
The levels of cortisol will negatively regulate the production by the anterior pituitary of ACTH and by the hypothalamus of CRH
Two Responses to Stress:
- The activation of the autonomic nervous system that leads to the release of adrenaline
- The activation of the HPA axis
The General Adaptation Syndrome
1- Alarm: facing the shock… requires a fast response
2- Resistance (adaptation): recovering or enduring the shock. Requires resistance and prolonged effort
3- If no recovery… exhaustion
1- Short Term Responses
Effects of norepinephrine & epinephrine
- -> Glycogen breakdown, increase in blood sugar (you want to give energy to muscles)
- -> Increase in blood pressure (make sure that all your organs are perfused with high pressure)
- -> Increase in breathing rate (make sure that you have oxygen and you release CO2)
- -> Change in blood flow: increase in alertness
- -> Decrease in digestion, excretion, reprod.
2- Long-term responses
Effects of glucocorticoids
- -> Proteins broken down, converted to glucose, increase in blood sugar (goal is to make more circulating glucose to sustain the stress response)
- -> Increase appetite and cravings ( so you have the energy to respond to the stress)
- -> Suppression of immune activity (because immune cells probably require some energy and this stress pathways shuts down anything which is not required to sustain the effort)
- If you are constantly stressed, you will keep breaking down proteins and suppress your immune system –> Dangerous
Cushing Syndrome
Long-term high levels of cortisol (hypercortisolism)
Complications associated with high cortisol
- Osteoporosis (fractures)
- Diabetes
- Frequent infections
- Loss of muscle mass and strength
Comment on hormonal levels: Negative feedback and hormonal oscillation
Negative Feedback Loop:
- Hormone accumulates
- Hormone does its action
- Hormone reaches a threshold level
- Negative feedback shuts down hormone
- Hormone decreases
Osmoregulations for corticosteroids
- Sensor: kidney filtration rate, drop in blood pressure/volume, renin/angiotensin
- Hormonal axis to regulate mineralocorticoids (salt reabsorption potassium excretion
- Water reabsorption Anti-Diuresis
The most known mineralocorticoid
Aldosterone
Aldosterone
Promotes salt reabsorption and potassium excretion. What is similar is that it promotes water reabsorption and is an antidiuretic.
Drop in blood pressure –> Renin angiotensin system activation –> aldosterone synthesis –> salt reabsorption, K+ excretion, water reabsorption (restoring or maintaining blood pressure and volume)
If you have high or low kidney filtration rate,
that will regulate this renin angiotensin pathway that leads to the production of mineralocorticoids
What regulates the production of aldosterone by the adrenal gland? (DRAW THE PICTURE)
The presence of the hormone angiotensin II.
Angiotensin I is converted in angiotensin II by an enzyme called ACE (angiotensin-converting enzyme)
- ACE is released constantly by the lungs
- Angiotensin I is produced by the action of an enzyme called angiotensinogen
- The liver produces angiotensinogen & puts it in circulation
- If your osmolarity and blood volume are okay, nothing happens to the angiotensinogen, but if there’s a drop in fluid volume or a drop in pressure, the kidney will sense that (because of a decrease in perfusion of the kidney or a decrease in infiltration rate) (it’s also the case if you have low filtrate NaCl concentration so it’s actually triggered if the osmolarity is low or there’s high potassium)
–> the kidney will produce renin into circulation and convert angiotensinogen into angiotensin I
Angiotensin II stimulates… (DRAW PICTURE)
- Vasoconstriction to maintain blood pressure
- in the kidney the reabsorption of both salt and water. This will mostly be in the distal tubule
