g proteins

GPCRs/7-transmembrane receptors (7TM receptors)

G-protein-coupled receptors (GPCRs) are the largest and most diverse group of membrane receptors in eukaryotes. 

Structure

  • single polypeptide chain comprising of seven transmembrane α-helices
  • extracellular N-terminal domain of varying length, 
  • intracellular C-terminal domain.
  • length of the extracellular N terminus and the location of the agonist binding domain determines family.
  • The long, third cytoplasmic loop couples to the G-protein 
  • Usually particular receptor subtypes couple selectively with particular G-proteins
  • For small molecules, such as noradrenaline, the ligand-binding domain of class A receptors is buried in the cleft between the α-helical segments within the membrane. Peptide ligands bind more superficially to the extracellular loops

G protein system

GPCRs interact with G proteins in the plasma membrane when an external signaling molecule binds to a GPCR, causes a conformational change in the GPCR.  G-proteins comprise a family of membrane-resident proteins
whose function is to recognise activated GPCRs and
pass on the message to the effector systems that generate
a cellular response. 

  • G proteins are specialized proteins with the ability to bind the nucleotides guanosine triphosphate (GTP) and guanosine diphosphate (GDP). 
  • The G proteins that associate with GPCRs are heterotrimeric, (alpha beta and gamma subunits)
  •  alpha and gamma are attached to the plasma membrane by lipid anchors 
  • Trimer in resting state 
  • activated alpha monomer and beta/gamma dimer

Guanine nucleotides bind to the α subunit, which has enzymic activity, catalysing the conversion of GTP to GDP. The β and γ subunits remain together as a βγ complex. All three subunits are anchored to the membrane through a fatty acid chain, coupled to the G-protein through a reaction known as prenylation.

  • G-proteins are freely diffusible so a single pool of G-protein in a cell can interact with several different receptors and effectors 
  • When GPCR is activated by an agonist, a conformational change causes it to acquire high affinity for αβγ (G protein)
  • bound GDP dissociates and is replaced with GTP, which in turn causes dissociation of the G-protein trimer, releasing α-GTP and βγ subunits - the ‘active’ forms of the G-protein
  • which diffuse in the membrane and can associate with various enzymes and ion channels
  • Signalling is terminated on hydrolysis of GTP to GDP through the GTPase activity of the α subunit.
  • resulting α–GDP dissociates from the effector, and reunites with βγ
  • Attachment of the α subunit to an effector molecule increases its GTPase activity
  • GTP hydrolysis is termination –> activation of the effector tends to be self-limiting

Second messenger targets for G proteins

Main targets:

  • Adenylyl cyclase (responsible for cAMP formation)
  • Phospholipase C (inositol phosphate and diacylglycerol (DAG) formation)
  • Ion channels, particularly calcium and potassium channels
  • Rho A/Rho kinase (system controlling the activity of many signalling pathways for cell growth and proliferation, smooth muscle contraction, etc.)
  • Mitogen-activated protein kinase (MAP kinase) system controlling cell functions eg division.

(notes on these coming soon)

Pre-T Trans* Guys: Nutrition Tips

To naturally decrease your estrogen levels, you can eat/drink:

  • VEGETABLES: Cauliflower, cabbage, lettuce, broccoli, carrots and anything really green!
  • Citrusy things like oranges, lemons, etc. 
  • Nuts (no pun intended)
  • Onions
  • Garlic
  • Olives/Olive Oil
  • Avocados
  • ASPARAGUS 
  • Flax Seeds
  • Blueberries
  • Fish

Exercises:

  • Swimming
  • Boxing
  • Biking
  • Cardio

Protein Info:

  • 45-70 g of protein a day is normal for males
  • Protein shakes!! (Soy increases estrogen levels, so if you are vegan and you are using protein shakes, I recommend rice shakes) Remember that with protein shakes, if you do not exercise as much as you’re meant to while you’re drinking them, then the muscle will turn right intofat and for most trans* guys, the fat will distribute itself into your thighs, butt, hips, etc. If you’re looking to lose weight, make sure the protein shake you decide to use is high in protein, but low in carbs and calories.
  • It’s recommended that you take your shake 30 minutes AFTER you work out, if you’re not going to work out one day, take it first thing in the morning

A lot of trans* guys are looking to gain weight, and the best way to do that is to obviously eat a lot of carbohydrates and proteins. They not only boost your energy, but help you achieve the weight you’re hoping for. Remember, decreasing your estrogen levels will help you with muscle mass. Decreasing your stress level will decrease your estrogen levels, thus increasing your testosterone levels and making it easier for you to achieve the body you’re working towards.

Also: Alcohol converts your testosterone back into estrogen, so if you’re a trans* guy who likes to drink, it’s probably not going to help out much!

I got most of the information for this post from this video.

Neurotransmitters

Central nervous system

  • Glutamate 
  • GABA 
  • Glycine 
  • Dopamine 
  • Serotonin 
  • Noradrenaline 
  • Histamine 
  • Orexin 
  • Endorphins 

Peripheral nervous system 

  • Noradrenaline 
  • Acetylcholine 

Neurotransmitter synthesis/packaging 

  • Some neurotransmitters are readily available amino acids eg Glutamate, glycine 
  • Some are synthesised by the cells that secrete them eg GABA, noradrenaline, dopamine 

Noradrenaline synthesis:

Packaging

  • In the presynapse, neurotransmitter is contained in vesicles 
  • The neurotransmitter must be packaged into the vesicle ready for release 
  • Uses transporters and proton gradients to package 

[packaging and release - above]

  • Neurotransmitter release is quantal – Each vesicle contains the same amount of neurotransmitter 
  • Therefore it is the number of vesicles fusing which determines the post synaptic potentials 
  • membranes must fuse for release - membrane fusion is energetically unfavourable so must be catalysed by something

SNARE Hypothesis 

  • Proteins on the presynaptic membrane ‘grab’ proteins on the vesicle membrane 
  • These SNARE proteins pull the two membranes close together 
  • SNARE proteins provide most of the energy for membrane fusion
  • v-SNARE (VAMP2) – on vesicle membrane 
  • t-SNAREs (syntaxin1A, SNAP-25) on target membrane 
  • Bind together to make SNARE complex 
  •  SNARE ‘zippering’ forces the membranes close together 
  • Spontaneous, highly energetically favourable 
  • Once assembled, they require ATP hydrolysis to separate them 
  •  Ca2+ binding to synaptotagmin provides extra energy to fuse the membranes

Neurotransmitter release

  • synaptic vesicle release sites are highly organised and regulated
  • exocytose into synaptic cleft

presynaptic active zone:


Neurotransmitter detection

  • Ionotropic (ion channel coupled) – Glutamate, GABA, Glycine 
  • Metabotropic (G-protein coupled) – monoamines, histamine etc. 
  • Some have both kinds, e.g. glutamate, GABA 
  • Ionotropic responses are faster 
  • Metabotropic responses can have more diverse effects 

Glutamate receptors

  • Glutamate is the main excitatory neurotransmitter in the brain 
  • Three classes of ionotropic receptor – AMPA – NMDA – Kainate 
  •  Named after pharmacological agonists 
  • All let in positive ions when they bind glutamate 
  • Glutamate also has a family of metabotropic receptors – mGluRs – These modulate neurotransmission 

AMPA Receptors 

  •  Main fast excitatory receptor 
  • Strength of a synapse is largely determined by its complement of AMPARs
  •  More AMPAR in the post-synaptic membrane = stronger synaptic transmission 

NMDA Receptors 

  • Minor role in postsynaptic firing 
  • Major role is in synaptic plasticity 
  • NMDA receptors are calcium permeable 
  • require strong neurotransmitter release to open 

anonymous asked:

Can you tell us more about your vegan diet food alternatives and how it impacts your body goals? I have food sensitivities and can't digest whey protein and other supplements. I was surprised to hear that there are alternatives on your tumblr.

Certainly - I eat as many whole foods as possible. I eat a lot of beans & rice, tempeh, red lentils, and veggie pastas (black bean, red lentil, mixed veggie) for my protein. I sometimes eat fake meat if I need a change but I don’t really like it anyway.  Protein is also sneakily hidden all over so when you count your protein don’t forget those - they add up. Usually I aim for about 110 g of protein a day. Make sure you’re getting all amino acids (its easy). The internet is also FULL of plant based recipes. get into cooking cause that’s really the key.

Nuts are a really good snack and are really good for making sure you get your calories up. They also contain a lot of important nutrition. Fruit is a wonderful snack too. I keep a lot of frozen veggies so something i can make a quick snack from microwaving and seasoning them (peas, greens, broccoli). Sometimes ill even microwave a sweet potato and just eat that. Go for lots of variety in your foods.  If you’re having trouble knowing what you need to eat, download the app “Dr. Gregor’s Daily Dozen” - love it! 

I find a Vitamix very helpful; drinking your veggies is fun, tasty, and fast. It can make a surprising amount of foods smooth. When I add protein to shakes I buy powders from TrueNutrition (cheap and effective)

As for active performance. I feel generally more energized. Food is powerful so eating well feels good. I have become more trim since going plant-based because I eat less calories (fiber is filling). if there is any issue, it is that it is easy to not eat enough (for my goals). It’s not the worst thing, but I do need to make sure I am eating throughout the day. 

3

Coconutcake Baked Oatmeal

70 g oats
1 heaping tbsp coconutflour
10 g vanilla protein powder
1 tsp of each chia and flaxseeds
½ tsp baking powder
cinnamon
1 tsp maple syrup, agave nectar or other liquid sweetener
plantbased milk

How to:
mix all ingredients in an oven save bowl together. just use as much plantmilk until you have something like a creamy oatmeal constistence (shouldn’t be too liquid). Preheat your oven to 180°C. Add half a banana on top of your oatmeal and bake for around 20-25 minutes (when you touch the top with your fingers it shouldn’t be too soft, it sould feel more like a cake). Remove from your oven, let cool down for 2 minutes, add peanutbutter and enjoy warm! :)

PLEASE DO NOT REBLOG :)

Anti-cancer drugs - DNA targeting

Include alkylating agents, intercalating agents, and chain cutters.

Alkylating agents

  • Highly electrophilic species, looking for nucleophilic sites to attack, and forming covalent bonds to bases in DNA 
  • Prevent replication and transcription 
  • Toxic side effects (e.g. alkylation of proteins) 
  • Bind in the major groove of DNA
  • Both types cross-link DNA by covalently bonding to nitrogen of base pairs.
  • Binding of nucleic acid bases results in miscoding and distortion. 
  • Distortion of DNA prevents excision by HMG proteinspermanent damage. 
  • Transcription and replication prevented, tumour growth slows. 

Two electrophilic sites on an anticancer drug can cause interstrand and intrastrand cross-linking.

  • Preference for 1,2-GG or 1,2-GC linkage sites, with interstrand or intrastrand linkage, is dictated by drug chemical structure 
  • Other linkage adducts are possible. Eg 1,3-GCG, 1,2-GA. 
  • Monofunctional adducts are also possible 

Chlormethine (a nitrogen mustard)

  •  Chlormethine is highly reactive, toxic side effects. 
  • Lead compound for many less toxic mustard derivatives. 
  • Methyl (CH3 ) group has positive inductive effect – promotes loss of chloride – see mechanism 

Less toxic chlormethine analogues:

  • Melphalan:  e- withdrawing ring lowers Nu strength of N, less reactive drug, less side effects, less toxic. Mimics PhAla, carried into cells by transport proteins. 
  • Uracil mustard:  Uracil ring is e-withdrawing, less reactive alkylating agent. Mimics a nucleic acid base, concentrates in fast growing cells.
  • Cyclophosphamide:  Most commonly used alkylating agent, Non-toxic, orally active prodrug. Acrolein associated with toxicity.
  • Busulfan: Causes interstrand cross-linking. Sulphonate group withdraws electrons, adjacent carbon subject to Nu attack by DNA bases. 
  • Dacarbazine – A diazine:  Prodrug activated by oxidation in liver, decomposes to form methyldiazonium ion. Alkylates guanine groups 

INTERCALATING AGENTS

 Aminoacridines eg Proflavine

Antibiotics - Dactinomycin

  • Extra binding to sugar phosphate backbone by cyclic peptide 
  • Intercalates via minor groove of DNA double helix 
  • Prevents unwinding of DNA double helix 
  • Blocks transcription, blocks DNA-dependent RNA polymerase 

Anthracyclines eg Doxorubicin (adriamycin) 

  •  Extra binding to sugar phosphate backbone by NH3 Planar rings and Anthracyclines eg Doxorubicin (adriamycin) 
  • Intercalates via major groove of DNA double helix 
  •  A topoisomerase poison - blocks action of topoisomerase II by stabilising DNA-enzyme complex 

CHAIN CUTTERS 

Calicheamicin g1 I antitumour agent 

  •  Nucleophilic attack on trisulphide chain starts a rearrangement process. 
  • This interacts with DNA to generate a DNA diradical, which reacts with oxygen, resulting in chain cutting.

Bleomycins (BLM)

  • Highly active head, neck, testicular cancer (Hodgkin lymphoma) 
  • Single and double-strand cleavage of DNA with several reduced metal ions and O2 , Fe(II) highest in vivo activity. 
  • Three regions - 
  • bithiazole DNA binding domain (DBD) locks BLM into the minor groove, 
  • carbohydrate domain (CHD) H-bonds BLM to sugar phosphate of DNA 
  • metal binding domain (MBD) bonds to Fe(II)    

Mechanism

  • A reaction with hydrogen peroxide gives Fe(III) and hydroxyl radicals which abstract H atoms and cut the DNA chain. 
  • Fe2+ + H2O2 Fe3+ + OH. + OH− Fenton mechanism 

Lungs and skin have low levels of BLM hydrolase - higher sensitivity and toxicity. Pneumonitis occurs in about 10% of patients, progresses to pulmonary fibrosis. Over-expressed in malignant cells, resistance to bleomycin    

Summary of Anti-Tumour Specificity for DNA 

Major groove alkylators 

  • GG interstrand - N-mustards, nitrosoureas. 
  • GG intrastrand - methanesulphonates. 
  • GC-interstrand - nitrosoureas, triazines. 

Minor groove intercalators 

  • GG interstrand – anthracyclines. 
  • GC-interstrand – actinomycins, acridines. 

Minor groove chain cutters 

  • GC or GT intrastrand – bleomycins 

The Healthiest Chocolate Chip Cookie Ever

The perfect chocolate chip cookie recipe for anyone who is diabetic, gluten intolerant — or both.

Ava’s Chocolate Chip Cookies

Yields: 20 cookies

Ingredients:

½ cup unsalted organic almond butter (homemade or Living Tree Community Foods Organic Roasted Almond Butter)
2 tablespoons unsweetened applesauce
1 teaspoon vanilla extract
1 tablespoons honey
1/3 cup almond flour
½ cup cooked quinoa
1 tablespoons hemp seeds
1/3 cup bittersweet mini chocolate chips
Directions:

Preheat oven to 350 degrees.
Place all of the ingredients in a large bowl, mix and scoop out with a spoon onto a prepared baking sheet. Bake for 20 – 25 minutes. Let cool.
Enjoy with a big glass of unsweetened almond milk!
Nutritional information (Per Serving: 1 cookie): Calories: 80, Total Sugars: 3 g, Total Fat: 5 g, Saturated Fat: 1 g, Cholesterol: 0 mg, Protein: 2 g, Carbohydrate: 8 g, Dietary Fiber: 1 g, Sodium: 0 mg

https://www.yahoo.com/health/the-healthiest-chocolate-chip-cookie-ever-110283249033.html

carrot cake baked oatmeal

70 g quick oats
20 g coconutflour
10 g vanilla protein powder
1 tsp of each, chia and flaxseeds
cinnamon
baking powder
2 tbsp natural soy yogurt
½ finely grated carrot
1 tbsp maple syrup
water

How to:
just mix everything together and add as much water as you need until you have a thick porridge consistency. preheat your oven to 180°C and bake for around 25 minutes. If you want the oatmeal to be as orange as the one in the first picture, just add some tumeric to it! :)

PLEASE DO NOT REBLOG :)

2

So, today I learned that “G-proteins”, named after the guanine nucleotides they bind to, act as molecular switches inside cells, and “heterotrimeric” G proteins are activated by G protein-coupled receptors. These G-proteins consist of alpha, beta and gamma subunits. G-alpha subunits, when inactivated, do some shit that I am too tired to explain.

I also discovered that I have a half decent view of a sunset from the library.

Write on! Or, sleep on…

Receptors intro - pharmacology

Drugs act at four different levels

  • Molecular - immediate target for most drugs (eg propanolol binds to B-adregenic receptors)
  • Cellular - biochemical and other consequent effects (eg propanolol reduces Ca2+)
  • Tissue - function altered (eg propanolol decreases myocardial contractility) 
  • System - function altered (eg propanolol reduces need for cardiac output, easing pressure on cardiovascular system)

Most drug targets are proteins 

  • Receptors - for transmitter substances and hormones
  • Enzymes
  • Transport systems - ion channels, active transport
  • Substrates
  • Second messengers 
  • Antibodies 

some drugs act on nucleic acids.

Receptors

“Receptors are the sensing elements in the system of chemical communication that coordinate the function of all the different cells in the body.”

Upon recognition of ligand (chemical signalling molecule), receptor proteins transmit the signal into a biochemical change in the target cell.

Cell surface receptors

Hydrophilic transmitters act on cell surface receptors

  • peptides
  • most neurotransmitters 
  • other small molecules

All cell surface receptors are transmembrane proteins 

  • Extracellular domain - receptor site
  • transmembrane domain
  • intracellular domain - catalyic/coupling site, only present on certain receptors

Intracellular receptors 

Hydrophobic (lipid soluble) transmitters act on intracellular receptors

  • steroids
  • thyroid hormones
  • vitamin D

Drug interaction with receptors 

  • Agonist - activates receptor
  • Antagonist - binds to receptor without activating, thus presenting activation
  • Affinity - measure of how avidly a drug binds with receptor

Side effects occur when drugs bind to more than one type of receptor. Some bind irreversibly and most bind with weak intermolecular bonds. An equilibrium arises between bound and unbound drug.

(notes on types of receptor to follow - overview:)

Ligand-gated ion channels: open or close upon binding of a ligand

G-protein-coupled receptors: Transmembrane receptor protein that stimulates a GTP-binding signal transducer protein (G-protein) which in turn generates an intracellular second messenger

Nuclear receptors: Lipid soluble ligand that crosses the cell membrane and acts on an intracellular receptor

Kinase-linked receptors: Transmembrane receptor proteins with intrinsic or associated kinase activity which is allosterically regulated by a ligand that binds to the receptor’s extracellular domain

Chia Seed Protein Pudding: I’d normally be the first person to say “you do not need chia seeds” but when you’re walking down the aisles in Costco and find a 2 lb bag for the same $6 price your grocery is asking for a 6 oz sachet, it’s looking a little more affordable. 

If you’ve followed me for awhile, you might have realized that I’m lactose intolerant. This isn’t a novel idea; it’s everywhere, but what I like to do with chia seeds is essentially make a yogurt replacement. Not only in terms of consistency and calcium (chia seeds are fairly calcium rich), but I also add some protein powder to get the protein you’d want from the ever popular Greek yogurt.

Now, if your protein powder is flavored it might end at:

  • 2 cups plant milk
  • 60g chia seeds
  • 2 scoops protein powder

Blend, blend, blend! 

But, I use unflavored and unsweetened powder. I also like changing flavors often. This week I made a caramel macchiato chia seed protein pudding!

  • 1 cup unsweetened almond milk
  • 1 cup freshly brewed coffee
  • 60 g chia seeds
  • 2 scoops of unflavored protein powder
  • ½ cup stevia
  • 2 TBSP salted caramel coffee flavor syrup (Torani and Da Vinci both make sugar free if that’s important to you)

Directions: Blend milk, coffee, protein powder, syrup, and sweetener together for 30 seconds. Add in chia seeds and blend again in 30-second increments until it begins to thicken. Let sit in the fridge for several hours to overnight before serving. Recipe makes 4 servings. 

Mine comes out at 12 g of protein per serving and 20% your DV of calcium. This makes my lactose intolerant bones feel a little bit stronger now!

2

Fluffy glutenfree Tumeric Pancakes

75 g buckwheat flour
10 g sweet lupino flour
15 g vanilla protein powder
¾ tsp baking powder
½ tsp Tumeric
½ banana, mashed
1-2 tsp flaxseeds
water or plant milk

How to:
First, just mix all dry ingredients together. Mash banana and add dry ingredients plus water or milk. Add as much liquid until you have a creamy thick (!) batter. Heat a pan on Medium to high heat and bake every pancakes until brownish from both sides 🙂 that’s it!


PLEASE DO NOT REBLOG :)

Keto pizza ❤


@exercisecatsandketo said she made pizza with coconut flour… I ran out of almond flour some time ago and really needed pizza today.

I tried it and honestly can’t tell the difference between almond or coconut flour here. No coconut taste. It’s mostly mozzarella anyway and I believe I could use sand or sawdust and it would be the same 😂

I’m copying my recipe:

For the crust:

- 180 g mozzarella cheese (melted)

- 50 g almond or coconut flour

- 1 tbsp psyllium husk

- 15 g parmesan cheese (grated)

- 1 egg

- salt, oregano

First mix together all the ingredients except mozzarella and then add that too. You get a ball that looks funny and uneven, but ignore your doubts.

Press it onto parchament paper and put another paper on top then use rolling pin (or a glass or just your hands) to spread it. Remove the top paper. Broil it for about 5 min in very hot oven (250 C or 480 F) until lightly brown. Flip the crust (you can use the extra parchment paper) and broil for another 5 min.

Take it out and top with sauce, cheese and anything else you like. Back to the oven until cheese starts to bubble.

Half of it (I can’t eat less) has: 670 kcal, 11 g of carbs, 42 g of fat and 53 g of protein.
[AP Bio] TEST FOUR: Cellular Respiration

REGULAR HIGHLIGHTED VERSION CAN BE FOUND HERE

(*IMPORTANT: a lot of the format and diagrams got really messed up on here, I apologize)

cellular respiration = breakdown of fuel to generate ATP for work

3 Key Pathways: 1) glycolysis, 2) citric acid cycle, & 3) oxidative phosphorylation/electron transport chain (ETC)

characteristics: waste products = CO2 & H2O, catabolic pathway

Oxidation-Reduction Reactions

AKA “redox” reactions

-the transfer of electrons
-> can be complete or partial (in cases of covalent bond sharing)

oxidation = the loss of electrons

reduction = the gaining of electrons

“oxidizing” agent = substance that accepts electrons from another

“reducing” agent = substance that gives up/“donates” electrons to another

*the transfer of electrons, as they are pulled down the energy gradient from a molecule of low EN -> molecule of high EN, is exergonic as this transfer causes the electrons to release potential energy

-> can be harvested for work! (INDIRECTLY)

-> cell resp. is all about understanding how the flow of electrons & protons controls the whole process!

Brief Overview of Cell Respiration

Fuel Reactant
Glucose Oxygen
Oxidized Reduced
Reducing Agent Oxidizing Agent
Goodbye electrons! :-c Hello electrons! c-:

oxidized (loses e’s)

C H 0 + 6O  -> 6CO  + 6H 0 + energy (ATP + heat)

reduced (gains e’s)

*typically carbs are used but lipids (fats) can also be used due to the large amount of H’s in the hydrocarbon tails, & actually generate a lot of energy

fun tidbit:
*the metabolic waste, C0 , is breathed out by the body and then taken in by plants, which use it to produce glucose -> thus the circle spins on & on

How Glucose is Broken Down

*energy cannot be efficiently harvested for work all at once, so rather it is broken down in a series of steps, called “stepwise energy harvesting”

1) Electrons taken from glucose (also, 1 proton) are given to Nicotinamide Adenine Dinucelotide (NAD+), a coenzyme
-> NAD+ is an oxidizing agent, and so therefore is able to accept electrons

2) NAD+ is an “empty taxi cab”. The enzyme dehydrogenase oxidizes food (such as glucose) to get the 2 e’s & 2 p’s (H+’s) so they can be given to NAD+.

3) NAD+ is reduced by accepting electrons, and becomes NADH. NADH is a “full taxi cab”, containing 2 e’s & 1 p (H+). The other H+ is released into the cytosol.
-> Each NADH represents potential energy that can be indirectly used to power the synthesis of ATP

4) NADH passes the e’s onto the electron transport chain (ETC). The ETC then passes the e’s on in a series of controlled steps to the oxygen molecules that pull them down the chain (b/c of its high EN). This process yields energy that can be used to re-generate ATP.

Stages of Cellular Respiration

1) Glycolysis- breakdown of glucose (“glyco” = glucose, “lysis” = breakdown)

2) Citric Acid Cycle- completes the breakdown into 2 molecules of pyruvate of glucose (AKA Krebs Cycle)

3) Electron Transport Chain (ETC)- accounts for most of ATP synthesis

 ————————————————————————————————-

(*the following diagram got really messed up on here, I apologize)

electrons carried via
NADH                                                                          electrons carried
                                                                                  via NADH & FADH2

Glycolysis                                                
1 glucose -> 2 pyruvate ——————-> citric acid                                                 (SPLIT)                                                    cycle                    electron transport
                                                                                               and chemiosmosis
                                            
                                                       (mitochondrion)
(cytosol)

                                                                                                         ATPs                                                                              ATP
   ATP

substrate-level                                  substrate-level                                             phosphorylation                                phosphorylation                                                                                                                                                                                                                                                                              *oxidative
                                                                                                phosphorylation*

2 ATPs were invested,                                                       results in a LOT more
and 4 in total produced, so            results in 2 ATPs                       ATPs
NET = 2 ATPs                                    now: total 6
                                                             NET = 4                   produces NET = 32-                                                                                                        34 ATPs                                                                                                                

Glycolysis


-occurs in the cytosol

                        [high] G     outside/ECM

facilitated
diffusion             *Integral protein & cell membrane
(no energy)    
                         [low]  G      inside/cytosol

G-p <— phosphate is added (neg. charge “locks” glucose inside cell!)



-requires the energy investment of 2 ATPs



Energy Investment Phase

1- 2 ATPs invested

2- Enzymes take phosphates off ADPs

3- Series of steps where phosphates are taken off ATPs & then phosphorylated to molecules (TWICE) that are slightly changed each step

4- Eventually split into 2 3-carbon sugars (“G3Ps”)

Energy Yielding Phase


1- As the 2 G3Ps are oxidized, NAD+ is reduced to NADH -> this contributes to the ETC by carrying electrons (& protons)!

2- After, there is an “intermediate molecule” (ex: 1,3-biphosphoglycerate -> don’t need to know exact molecule) that has a phosphate. This phosphate is taken off and given to 2 ADPs to become 2 ATPs. This happens twice within the series of steps in this phase. Also, at one point, 2 H2Os are taken out.

3- Eventually transformed into 2 pyruvates

4- A total of 4 ATPs are made in this “payoff” phase. However, since 2 were invested originally, there is only a net of  2 ATPs.

                                      C3H3O3
C6H1206                    -pyruvates-
                                      C3H3O3

(*this diagram got really messed up on here too)

Energy Investment Phase



Glucose



2 ADP + 2 p <—————— 2 ATP used



Energy Payoff


Phase      4 ADP +


                    4 p          ———————->   4 ATP    formed



2 NAD+ + 4 e


+ 4 H+                   —————————>   2 NADH + 2 H+



                 


                                                    ————–> 2 Pyruvate + 2 H2O




Net                     Glucose ————> 2 Pyruvate + 2 H2O



4 ATP formed - 2 ATP used ——-> 2 ATP



2 NAD+ + 4 e + H + ———-> 2 NADH + 2 H+




Substrate-Level Phosphorylation

-not as efficient in producing ATP as oxidative phosphorylation

-used in both glycolysis & krebs/citric acid cycle

Citric Acid Cycle

-AKA “Krebs” Cycle

-COMPLETES energy-yielding oxidation of the organic molecules (ex: glucose)

-BEFORE the cycle can begin, the 2 Pyruvates must be converted to Acetyl CoA -> this links the cycle to glycolysis!

1) The 2 Pyruvates are oxidized and enter the Mitochondrion via a Transport Protein

2) CO2 is released (lungs -> exhale)

3) NAD+ is reduced to NADH & the e’s & p’s (H+’s) are stripped

4) A Coenzyme helps with the conversion to Acetyl CoA

-CAC uses BOTH molecules of pyruvate
*cycle goes around TWICE!

*CITRIC ACID CYCLE SUMMARY*

2 CO2 X 2 = 4 (released)

3 NADH X 2 = 6 (reduced)

1 FADH X 2 = 2 (reduced)

1 ATP X 2 = 2 (produced)

*appreciate the many redox Rx’s going on to keep the cycle going, changing Acetyl CoA all the way to Oxaloacetate!

Ex: R = NAD+ -> NADH
     O = any previous molecule!

ETC - Chemiosmosis - Oxidative Phosphorylation

-located at the inner mitochondrial membrane (like the plasma membrane, but different proteins!)                                                                              

*proteins are special ones made from the mtDNA (mitochondrial DNA)

*2 membranes! (DOUBLE)

PROTON MOTIVE FORCE

-facilitated diffusion

-a lot of energy & collisions b/c of flow of e’s

-*H’s come from glucose/pyruvate!

1) H+’s pumped out
2) O’s take H+’s to create H2O
3) Take protons in -> [low] guaranteed

-energy to power movement of H+ out!
(POTENTIAL ENERGY -> from redox Rx’s!)

-if O2 NOT present, H+’s cannot be moved/slid out -> b/c O2 is the final e acceptor w/ a high EN & the e’s release potential energy when moving down the gradient to O which powers the proton motive force

-keeps getting more EN as e’s pulled down/along chain

-H+’s move into ATP Synthase (important and moves protons BACK into matrix) protein -> active transport -> change of shape -> ATPs

fun tidbit:
-cyanide affects the enzyme that works w/ cytochrome oxidase, as it is an irreversible inhibitor that is tetravalent and desperate for a fourth bond, and therefore highly reactive (can shut down body systems and kill you within a matter of hours, and this is all due to bonding!)

ELECTRON TRANSPORT CHAIN

-oxidative phosphorylation & chemiosmosis couples the ETC to ATP synthesis

-located in cristae of mitochondrion

Pathway:

1) The components are proteins that exist in multiprotein complexes and are unique to the mitochondrion. These protein complexes alternate between reduced and oxidized states as they accept and donate electrons

2) Electrons drop in free energy as they go down the chain & are finally passed to O2 -> form H2O

3) NO ATP generated!!!!!

*THE FUNCTION OF THE ETC is to break the large free-energy drops from food to O2 into smaller steps that release energy in manageable amounts.

*the more redox Rx’s, the more energy is available.



CHEMIOSMOSIS

*the energy-coupling mechanism

1) Redox Rx’s in the ETC -> provide energy for the transport proteins to pump H+ from the mitochondrial matrix to the intermembrane space.

NEXT STEP IMMEDIATELY FOLLOWS

2) Proton Motive Force  develops as [H+] INC., w/i intermembrane space. Then, moves back across membrane & passes through channels in ATP Synthase.

3) ATP Synthase transports H+ BACK into matrix.

4) ATP Synthase uses exergonic flow of H+ to drive the phosphorylation of ADP -> ATP    (endergonic).

*chemiosmosis = use of energy in H+ chemical gradient to drive ADP phosphorylation

Fermentation

*enables some cells to produce ATP w/o the use of oxygen!

How can food be oxidized w/o oxygen?

-NAD+ is actually the oxidizing agent of glucose. A net of 2 ATPs are produced by substrate-level phosphorylation. Then, if there IS oxygen, more (a lot of) ATP can be produced when NADH passes the removed e’s from glucose to the ETC & oxidative phosphorylation occurs.

*glycolysis STILL produces 2 ATP whether O is present of not, though!

(either aerobic or anaerobic)


-fermentation is the anaerobic catabolism of nutrients

-fermentation = the extension of glycolysis that can generate ATP solely by substrate-level phosphorylation
-> *as long as there is a sufficient supply of NAD+ to accept e’s during the oxidation step of glycolysis

-NAD+ needs to be recycled from NADH

Aerobic Anaerobic
Recycled by the transfer Recycled by the transfer of electrons from NADH to Pyruvate (end product of glycolysis!)
of electrons to the ETC

TYPES OF FERMENTATION

fermentation = glycolysis + Rx’s that regenerate NAD+ (transfer of electrons from NADH -> Pyruvate)

Alcohol Fermentation = Pyruvate converted to Ethanol

1) RELEASES CO2 from Pyruvate
-> converted to 2-carbon compound “acetaldehyde”

2) Acetaldehyde is reduced by NADH to Ethanol

-regenerate supply of NAD+ needed

*many bacteria carry out alcohol fermentation under anaerobic conditions, also fungi (ex: yeast)

fun tidbit:

yeast -> used for 1,000’s of years by humans for brewing, wine-making, baking (bread, gases released create bubbles that allow it to rise), etc.

Lactic Acid Fermentation = Pyruvate reduced DIRECTLY by NADH - > forms Lactate (ionized form of lactic acid) as end product -> NO release of CO2

*certain fungi & bacteria used to make cheese & yogurt

*other microbial fermentation used to make acetone & methanol (methyl alcohol)

1) When O is scarce, human muscle cells can still make ATP by using lactic acid fermentation.

2) Strenuous exercise -> sugar catabolism for ATP production outpaces muscle’s supply of O from blood

3) Cells switch from aerobic respiration to fermentation -> creates lactate -> buildup of lactate can cause muscle fatigue and pain!

4) Lactate is gradually carried away by the blood to the liver -> converted back to pyruvate by liver cells

*facultative anaerobes = make enough ATP to survive using either fermentation or respiration (ex: our muscle cells!)
-> consume sugar at faster rate when fermenting to make the same amount

*Pyruvate is a “FORK IN THE ROAD”

3

I got myself a Happy Meal – because I’m an adult but I deserve to be happy too goddamnit – and it’s got all kinds of Smurf fitspo (Smurfspo?).

First of all, as a child of the 80s, I’m really happy that Smurfs are still culturally relevant.

It’s actually a fairly healthy meal. A cheeseburger, apple slices, milk, and yogurt works out to 460 calories, 59 g carbohydrates, 14 g fat and 25 g protein.