Exam 2: Biochem 2- Fill in the Blank----CREATED/EDITED BY JENNY T. BIOCHEM TUTOR 1. Glycerol Phosphate Shuttle (In the Exam 1 review) a. Malate-Aspartate shuttle: i. Is a similar shuttle as the glycerol phosphate but happens exclusively in 2 places 1. ___cardiac cells_________________ and _____Hepatocytes_________________ ii. This shuttle is reversible iii. Transfers reducing power from the __cytosol__________ to the matrix iv. Produces ____3____ ATPs in the Electron Transport System using this reducing agent____NADH_________ 2. Pasture Effect a. This is an observation of a system that is switching from anaerobic __aerobic___________ i. When we add oxygen to a system 2 things are noted 1. Lactate production____ decrease______________ (.) 2. Rate of glucose consumption __decrease____________ (,) a. This is due to the fact that when we switch to aerobic we make more ATP per glucose than if we were anaerobic. 3. Creatine and Creatine Phosphate (Cr-P) a. Cr-P is a ____high________ (low/high) energy compound i. It is derived from Creatine getting a phosphate group from ___ATP____________ b. Cr-P can lose a inorganic phosphate and turn back to __creatine_____________ i. Or it can be turned into a metabolic waste product ____creatinine_________________ 1. This waste product is generally higher in ___males____________ (females/males) a. Why?____more muscle mass___________________ c. Cr-P has __more______(more/less) work potential than just ATP alone (G=-37.6kJ vs just -31kJ) 4. Fatty Acids (FA) a Fuel a. Diet and Storage i. Fats that we eat and fats that we store are the same form. This is as a ___TAG__________ ii. Fats have a ____high________(high/low) energy content at __9____ kcal/gram b. Digestion i. Begins in the ___Small intestine lumen_________________ 1. Need bile from the __Liver___________ (or from our storage in the _____Gallbladder________________) 2. This acts as an ____emsulfying_____agent to break up the triacylglycerol (TAG) into smaller pieces. There is no chemical digestion happening ii. Enzymes for FA digestion 1. __Pancreatic___ ___Lipase__ (another name Steapsin) will hydrolysis (break apart with water) the TAG. This enzyme is made in the __Pancreas__ but is used in the lumen a. This is only done partially meaning that we have some diacyl or monoacylglycerols being absorbed before it is completely hydrolyzed c. Once the pieces are absorbed we put them back together into a TAG and shove them in the core of a lipoprotein called a ___Chylomicron_________. i. These are carried via the ___lymphatic________ system because they are ________not soluble____(soluble/not soluble) in water. d. Catabolism (Break-down) i. We can use the fats we store for Energy. ii. The FAs are stored in the ___cytoplasm________(cytoplasm/mitochondrial matrix). 1. To enter the matrix we must add activate the FA by adding a __CoA________ to the end. a. This uses ___1____ ATP 2. Then we have to move the FA to the ___Mitochondria_____ (cytoplasm/mitochondria) a. Use __carnitine_____ as a shuttle across membrane Once in an aerobic environment we can break down the FA further via a process called ___beta oxidation______ e. -Oxidation i. Steps 1. ____Oxidize_________ (add a double bond) a. Oxidating agent used _____FAD+______________ 2. ____Hydrate_____________ (add water) 3. ____Oxidize_______________ (add another double bond) a. Oxidating agent used ____NAD+_________ 4. Cleavage a. 2 carbon piece that comes off the FA____Acetyl-CoA____________ ii. 3 types of Fatty acids 1. Even carbon Saturated ____NO________ (yes/no) double bonds 2. Even carbon Unsaturated ___YES_______(yes/no) double bonds. 3. Odd carbon iii. ATP, Acetyl-CoA, Reducing agent calculations 1. For even carbons saturated: (DRAW THESE OUT!) a. Example C16 Fatty acid i. Undergoes Oxidation ___7_______ times ii. # Acetyl-CoAs made____8_______worth ___12______ ATP a piece iii. # FADH2 made ___7_______ worth __2_____ ATP a piece iv. # NADH made ____7______ worth __3______ATP a piece 2. For even carbons unsaturated a. Example 18: 2 9, 12 Fatty acid i. This has how many double bonds__2_____ ii. Undergoes Oxidation ____8______ times iii. # Acetyl-CoAs made____9_______ worth ___12_____ ATP a piece iv. # FADH2 made ___6_______ worth ____2____ ATPs a piece 1. ** remember if we already have a double bond in a fatty acid when we get to those carbons to be cleaved off then we don’t have to add a double bond in the first place so we don’t need to do the 1st step of oxidation and we lose those reducing agents that we could have possibly made. v. #NADH made ___8_______ worth ____3____ATP a piece b. Note we lose 2 ATP per double bond in the Fatty Acid. 3. For Odd number of carbons a. Don’t worry about figuring out ATP for this b. Do -oxidation until you get to 3 carbon piece called___Propionyl-CoA_____ i. Add a _CO2___ using Biotin as cofactor and form_methymalonyl-CoA ii. Move methyl group and end up with _Succinyl-CoA______ 1. This can get right into the TCA cycle. f. **REMEMBER: when doing the ATP counts for even saturated or even unsaturated you need to subtract on from the total because you had to activate the FA to move it from the cytosol to the mitochondria and inorder to do this you had to use 1 ATP.** 5. Ketone Bodies (KB) a. Made in __Liver___________ and used in ____sk mm_____________ b. Name the 3 Keytone bodies and * the 2 that humans use exclusively i. ___acetoacetate__ ____-hydroxybuterate___ _acetate (only in severe Diabetes mellitus)___ c. Ketogenesis i. Starting material:_2____Acetyl-CoA_______________ ii. 5 carbon intermediate:__HMG-CoA_______________ iii. 1st KB made:__Acetoacetone_______________ 1. can be reduced using NADH to ___-Hydroxybuterate____________ d. Transported out of ___Liver_____ into the blood plasma i. Which KB is found in higher amounts in the blood?___-hydroxybuterate____________ 1. Why?___Higher reducing power (Hydrogens) or work potential________________ ii. Travel to lets say the skeletal muscle. e. Catabolism of KB i. This KB__ hydroxybuterate__ will be oxidized back to ___acetoacetate_____ to be used ii. Must have a Co-A added so we use___Succinyl-CoA_____ from the TCA cycle as a donor. iii. Eventually break into 2__acetyl-CoA_____ to be used in the __TCA____ cycle for making reducing agents and eventually ATP f. If excess KB build up in blood we get ____Ketoacidosis_________ 6. Amino Acids (AA) as Fuel a. Uses for AA i. ______Make proteins_______ ii. ____To make highly specialized molecular structure_________________ iii. ___Carbons for gluconeogenesis__________________ b. Digestion i. Begins in: __Stomach_________________ 1. Enzymes a. Pepsinogen ___Pepsin_____________ i. Made in the _Gastric Mucosal_________________ ii. Breaks this type of peptide linkage___Benzene rings__________ ii. Small Intestine 1. Proteolitc digestive enzymes a. _Trypsin____ __Chymotrypsin______ ___Procarboxypeptidase______ c. Absorption through the muscoal cells and then travel via the ___Hepatic portal vein_______ because AA (are/are not)___are_______ water soluble. d. Once in Liver AA have to be processed i. 2 ways to remove Nitrogen 1. Oxidative Deamination of Glutamate a. One product made that needs to be processed in the urea cycle ___NH3_____ 2. Transamination (all other AAs) (Change one AA into 1 of 3 to be dealt with later) a. Write out general formula for transaminations i. __AA____ + ___ ketoacid__ _AA____ + __ ketoacid______ b. 3 sets of AA and -Ketoacid that we can used to help turn all AA into something else i. Alanine __Pyruvate___________ ii. __Aspartate_______ OAA (oxaloacetate) iii. Glutamine ___keto-gluterate__________ c. B-vitamin cofactor needed for these reactions ____B-6 Pyrodioxal Phosphate__ e. Types of AA i. Name the 2 ketogenic AA: ___Leucine________ and ______Lysine________ 1. Meaning that their carbon structures can be made into ___ketone bodies__________ ii. The rest can be either Glucogenic (make glucose) or both 7. Amino Acids Degradation pathways a. Leucine is a __ketogenic_________ (glucogenic/ketogenic) AA i. 5 carbon intermediate of degradation:___HMG-CoA_____________ ii. Eventually is oxidized down to this ketone body___acetoacetone_______________ b. Phenylalanine (Phe) i. This is a AA that has a __Benzene______ ring in its structure so it is essential for making certain products that have this ring in its stucture. ii. Phe is reduced to the AA __tyrosine_____ using this enzyme __phenylanine hydroxylase___ 1. This product can be used to make these neurotransmitters:___Epi______ and __Norepi iii. If you are missing the enzyme to do the above reaction you have this disease ___PKU_____ 1. What kind of special diet is needed?_ no Phe and Tyrosine____________________ a. Why?___Phe will build up and developmental disorders will result. ___ 8. Urea Cycle: Nitrogen Disposal 1. Take any AA and either do Oxidative Denamination or Transaminate to get to Glutamate or Aspartate a. Take the NH3 from Oxidative Deamination and combine with ___CO2______ and ATP to form this ______Carbomyl-P___ (a high energy compound) that can be thrown into the urea cycle 2. The product of the cycle is __Urea_____________ i. Contains __2________ nitrogens ii. (Is /Is not) __Is________water soluble iii. Is excreted in the ___Urine____________ 9. Gluconeogenesis a. Making new __Glucose_____________ from non-carbohydrate starting material. b. Spend __6________ ATPs to get to glucose c. Like a reverse of this pathway___Glycolysis_________________ i. So ___Pyruvate________ Glucose d. Need to get pyruvate from the mitochondria into the __Cytosol______________ Pyruvate _ OAA____ Malate (this can cross inner membrane) Malate OAA __PEP______________ i. From PEP we can reverse most of the steps of glycolysis e. Until we get to F 16 BP F6P i. Uses a different enzyme than glycolysis ___F 16 Bisphosphatase_________________ 1. We can enhance or inhibit this enzyme depending on the amount of ATP in the system. a. ____ (high/low) ATP is when we want to inhibit new glucose i. thus the enzyme is __inhibited__________ (enhanced/inhibited) 1. When we inhibit F 16BPase we produce the intermediate F26BP and this will make sure that PFK1 is encouraged so that we get the conversion of F6P F16BP (glycolysis) b. ____ (high/low) ATP is when we want to make new glucose i. thus the enzyme is _Enhanced___________ (enhanced/inhibited) 1. the enhanced activity of F16BPase we produce less F26BP and this say that we need to make new glucose via gluconeogenesis. f. Get to G6P and need to change into Glucose to get into blood i. Cells that can do this conversion: mostly___Liver_____ and some __renal cells________ ii. Enzyme that does this conversion __Glucose 6 Phosphatase________________ 1. This enzyme has a lower Km than glucokinase (enzyme for glucose uptake from the blood into the hepatocytes) because it is G6P that is regulating the uptake of glucose from the blood. g. Starting material for Gluconeogenosis i. Can be Malate or anything oxidized to malate 1. List some possibilities a. __Pyruvate_ __OAA_ __Fumerate_ ___Succinate/Succinyl-CoA___ ii. This 3 carbon metabolite ____Lactate___________ iii. This 3 carbon Amino acid ___Alanine_____________ h. NOT going to be a starting material for gluconeognensis i. __Acetyl-CoA_______________ ii. ___Fatty Acids______________ iii. ___Leucine/Lysine______________ 10. Fed state and blood sugar requirements a. ___2-4_____ hours after eating: all glucose is burned b. __3-6______ hours after eating: hydrolyze glycogen in liver c. __5-6______ hours after eating: gluconeogeneiss slow because still some glycogen d. __16______ hours after eating: glycogen supply low, increase gluconeogensis e. __20-24_____ hours after eating: all gluconeogensis to maintain blood sugar 11. Cori Cycle a. Lactate is recovered after a making it in muscle by traveling in the _sk mm______ to the __Liver____ i. Some lactate used to make ___glucose____ via gluconeogenesis (5/6 of carbons) ii. The rest will go to the TCA cycle to make____ATP_________ (1/6 of carbons)