# Biochem ## 1. Electron trasport chain #### It's similar to the hot potato game - **Complex I (NADH D.H.)** converts NADH into NAD⁺ and gives those electrons to Flavin Mononucleotide to create FMNH2. The protones are sent out to the inner mithocondrial space - **Ubiquinone (CoQ-10)** Steals the electrons from the FMNH2 to convert Q into QH2. It's mobile, it can go after complex I and complex II - **Complex II (Succinate D.H.)** converts FADH2 into FAD, those electrons ger caught by Flavin Mononucleotide to make FMNH2. No protones are sent out. - **Ubiquinone (CoQ-10)** Steals the electrons from the FMNH2 to convert Q into QH2. It's mobile, it can go after complex I and complex II. - **Complex III (Coenzyme Q cytochrome-b oxioreductase)** It contains cytochrome-b and it gets the electrons from QH2 to convert Fe³⁺ into Fe²⁺. It sends protons out to the inner mithocondrial space. - **Cytochrome C** It has cytochrome-c and again it has Fe³⁺ that catches the electrons from the complex III to make Fe²⁺ - **Complex IV (Cytochrome oxidase)** It has cytochrome a + a3 and again it converts his Fe³⁺ to Fe²⁺ by catching the electrons from the previous step. It can use Cu as well and it sends protons out. - **Oxygen O2** It is the last acceptor, it gets those electrons from the complex IV and makes water ![Electron transport chain.png](../_resources/Electron transport chain.png) ## How to get the cytoplasmic NADH inside the mitochondria - **Malate-Aspartate Shuttle** Oxaloacetate that cannot cross the mitochondrial membrane, is converted into Malate, that can cross the membrane with the specific trasporter. This process gets the electrons from the NADH and puts them into the OAA to make Malate, while converting NADH into NAD⁺. Now Malate enters the mitochondria and gets converted back to OAA creating NADH from NAD⁺. OAA cannot leave the cell so it enters the Deamination process with α-Ketoglutarate to make Glutamate and Aspartate that can leave the cell through the same transporter Malate used. Once out Aspartate joins Glutamate to make OAA and α-Ketoglutarate so the cycle can repeat itself. ![Screenshot from 2022-03-22 12-14-36.png](../_resources/Screenshot from 2022-03-22 12-14-36.png) - **Glycerol-3P Shuttle** DHAP a byproduct of Glycolisis, that cannot cross the membrane, gets the electrons from NADH to make Glycerol-3P which stores those electrons and crosses the membrane to get those in. It then gets coverted back to DHAP because he donates those electrons to FAD to make FADH2. - **Fatty-Acyl-CoA** It gets inside the mitochondria via B-oxidation and is converted into Enoyl-CoA by donating the electrons to the FAD to make FADH2, that enters the electron transport chain. ![Screenshot from 2022-03-22 12-24-22.png](../_resources/Screenshot from 2022-03-22 12-24-22.png) ## The mechanism for making ATP ATP Synthase is made by 2 parts: F0 (the channel, the rotator and the rod) and F1 (the energy making place, the catalytic knod). When the protons enter in because of the gradient, the protein Arginine-210 gets those protons and swings them into the other channel so they can continue their way to the mithocondrial matrix. By doing that switch, when it swings back it makes the rotor to rotate, that makes the rod to rotate and the knod as well. This rotation stimulates the conversion of the F1 part, the knod, especially the beta part of it, from Loose state to Tight state, joining together ADP and Pi making ATP. For every molecule of NADH we get 3 ATP because a proton is sent out in Complex 1, 3 and 4; 3 protons out create 3 ATP. FADH2 in the other hand only creates 2 ATP beacause it enters the electron trasport chain in the complex 2, which doesn't send out protons, and continues to complex 3 and 4, so that's only 2 protons sent out per molecule. ![Screenshot from 2022-03-24 12-08-15.png](../_resources/Screenshot from 2022-03-24 12-08-15.png) ## Summary of energy created 1 molecule of glucose creates 2 ATP and 2 NADH through Glicolysis. The Transition step makes 2 NADH. Another 6 NADH are created in the Krebs cycle alongside with 2 FADH2 and 2 ATP. The total is 10 NADH, 2 FADH2 and 4 ATP. 10x2,5 --- ## 2. Glucose transporters types GLUT 1: Blood, Fetus and Blood Brain Barrier GLUT 2: Kidney, Liver and Pancreas GLUT 3: Placenta, Neurons and Kidneys GLUT 4: Muscle and Fat Adipose Tissue ![Screenshot from 2022-03-19 11-53-50.png](../_resources/Screenshot from 2022-03-19 11-53-50.png) --- ## 3. Glycogen metabolism ### Glycogenesis #### Fed state. Allosteric Regulation: Activated by ↑G-6P Glucose --> Glucose-6P --> Glucose-1P UTP --> UMP + P-P (pyrophosphate) Glucose 1-P + UMP => UDP-Glucose UDP-Glucose + Glycogenin => Glycogenin-(Glucose)8 + (UDP)8. **without any enzyme** **Glycogen synthase** continues the process of adding Glucose to the chain and releasing UDPs... **Branching enzyme** cuts the alpha-1,4 glycosidic bond and transfers 7 glucose molecules to add them to another part of the chain with a alpha-1,6 glycosidic bond. Glycogen Synthase continues to polymerise the Glucose. Glycogen global structure forms a sphere with the Glycogenin in the centre. ### Glycogenolisis #### Fasting state. Allosteric Regulation: Inactivated by ↑G-6P, ↑ATP and ↑Glucose (only in the liver) **Glycogen phosphorilase** is an enzyme that attacks the alpha-1,4 and adds a phosphate to the carbon 1 of the glucose => Glucose-1P It can act until 4 glucose molecules from an alpha-1,6 glycosidic bond. The **Debranching enzyme** is in charged to get those 3 extra glucose near to the one with the alpha-1,6 bond to put them into another chain creating an alpha-1,4 glycosidic bond. Then it cuts the alpha-1,6 bond releasing free Glucose that can leave the cell. G-1P cannot leave the cell, it gets converted to G-6P by action of the **phospoglucomutase.** G-6P is used for energy in muscle or can be released into the bloodstream by converting it to free glucose in the liver, using **Glucose-6Phosphatase** in the endoplasmic reticulum. ### Hormonal Regulation #### Glycogenolisis When there are low blood glucose levels: glucagon, epinephrine, norepinephrine or cortisol get close to the cell and they bind to a G-protein receptor. It has 2 pathways now: 1. once activated by GTP it can convert ATP to **cAMP** through adenolate cyclase. cAMP activates **Protein Kinase A (PKA)**. PKA then phosphorilates Phosphorilase Kinase B and activates it to **Phosphorilase Kinase A**. Phosphorilase Kinase A puts phosphates in Glycogen Phosphorylase activating it and starting Glycogenolisis. 2. Epinephrine and Norepinephrine bind to another G-Protein, Gq that binds to GTP and gets active activating the **PhosphoLypaseC (PLC)** on the membrane. PLC breaks down **PIP2** into Diacilglycerol (**DAG**) and **IP3** that pomp out the **Ca²⁺** from the Endoplasmic Reticulum, that binds to the **Calmodulin** activating the Phosphorilase Kinase B to **Phosphorilase Kinase A** that activates Glycogen Phosphorilase activating Glycogenolisis Protein Kinase A also phosphorilates Glycogen Synthase, passing from A form to B form, deactivating it. #### Glycogenesis **Insulin** activates a tyrosine receptor that activates the **PhosphoProteinPhosphatases (PPP)**, their role is to absorb / steal the phosphates. They remove phosphates from the Glycogen Synthase B to activate it making **Glycogen Synthase A** so it can then initiate Glycogenesis. They also remove phosphates from Phosphorilase Kinase A converting it into B and from the Glycogen Phosphorilase **inactivating it** so it cannot make glycogenolisis ![Screenshot from 2022-03-10 19-04-27.png](../_resources/Screenshot from 2022-03-10 19-04-27.png) --- ## 4.