BCH4024 Exam 2 Notes PDF

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Slide 1: -

Red: intermediates (OAA, alpha-KG) Know what they are the alpha-ketoacids of These three metabolites make the entire system work Pyruvate has a lot of C-C bond breakage in citric acid cycle, used that energy to make ATP Know where they are located in pathways

Slide 2: - Proteolysis: breakdown of proteins - Reuse amino acids, when old and damaged proteins are removed - Different stages of cell cycle may use proteolysis o In order to go from one stage to the other proteolysis may be used to cleave proteins - Make limited amount of amino acids - The reason your muscle still works at the gym when it gets hot, is because most proteins involved in contraction contain high amount of hydrophobic AA, when it gets hot the -t delta S provides stability - Nucleotides are derivatives of AA

Slide 3: - Not going to be asked numbers on exam - You get essential and non-essential AA from eating protein - Non-essential because they can be made, essential because we can only get them from out diet - Conditionally essential – can be made; under conditions of very fast growth, Arg needs to be additionally taken in from our diet because the amount our body can make is not sufficient o Tyr is needed when there isn’t enough Phe to make Tyr, Tyr must be in diet o Met is needed to make Cys; if we do not have enough Met, Cys must be in diet

Slide 4: - Break down few proteins in saliva, most will be broken down in the stomach. - Variety of enzymes needed in the stomach to break down proteins - Amino acids, Dipeptides and tripeptides are produced

Slide 5: - If you were to absorb proteins, you would be absorbing foreign proteins which are called immunogens – foreign bodies that our body will attack - If you send foreign proteins into the body, the antibodies will multiply and attack the antigenic protein – breaking down the proteins, we have destroyed the sequencing and they can be used - Zymogens are released on neuronal control – neurons go to cells producing zymogens, stimulating the secretion of them into the small intestine – only become active in the small intestine, to prevent from chewing up the pancreas - Damage to pancreas begins chewing up the pancreas, feeling pain in neurons – extreme pain can cause death - Proteins written from – amino to carboxyl ends - Enterokinase converts trypsinogen into active form trypsin - Pro-carboxypeptidase – section of peptide removed and becomes active in the intestine

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Zymogen made on ribosomes As mRNA is being read, the protein can penetrate into the lumen of the ER ER is oxidizing environment Once in lumen, undergoes proteolysis, becomes active Autophagy – eating self NOTE: pepsin active at pH 1-3

Slide 7: - Red – zymogen, inactive chymotrypsinogen - Trypsin cleaves chymotrypsinogen into weakly active enzyme, cleaved by chymotrypsin and makes a second cut. Once two cleavages occur it becomes fully active - First form has no oxy-anion hole

Slide 21: - SLIDES: slide 17 & slide 26 - GDH highly regulated enzyme – if you had 14 of these enzymes, and had to have DNA that made each of these, you would risk that one might mutate – if you have a mutation in one GDH that affects activity, the individual will not survive – 14 provides higher risk - Body creates one enzyme that is highly regulated, pairs with transaminase - Ammonia produced in the mitochondria – GDH solely in mitochondria - In opposite direction, uses NADPH not NADH, because there is an abundance of NADPH and not very much NADH

Slide 23: - Enzyme plays a key role in readjusting energy state of every cell in the body - Protein synthesis uses a lot of ATP and GTP – lowers energy state back to normal - If you have low energy – GTP is activated; a-KG enters TCA cycle to make more ATP - Low pH – enzyme binds NADH, high pH – prefers NADPH - L & D carry out same reaction, one carries out ONLY on L AA’s, other reacts ONLY on D AA’s - Enzymes always return to the same form - These only account for a few percent of all AA degradation because H2O2 is dangerous and you do not want to create a lot of it - During storage, L-AA’s get turned into D-AA’s - FMN = very similar to NAD

Slide 24: - Glutaminase is only found in mitochondria

Slide 25: - Cannot be in the same location because they would be wasting ATP - FUTILE cycle – pointlessly hydrolyze ATP - Can never be together

Slide 26: - Histidine – elimination reaction - Histidine ammonia lyase: forms double bond + ammonia - STAR MOLECULES

Slide 27: - Some AA when degraded create keto acids that lead to the production of sugars - Some AA, side chains, will form fats (keto acids) - Some AA can make both sugars and fats

Slide 28: -

Assimilated: made into other metabolites High concentrations are toxic Ammonia can cross membranes because it is neutrally charged High levels of ammonia cause coma or death High levels ammonia àa-KG is decreased through first reaction No questionson glycine synthase NH3 or NH4 are written as the same thing unless speaking of particular reaction

Slide 29: - Body makes a lot of glutamine – nitrogen ends up in about 50 other molecules in our body, large N in diagram, glutamine has donated that N into that position in a single step – other N’s were provided from glutamine in more than one step

Slide 30: -

Oxygen attacks ATP – connects to phosphate group – phosphate intermediate Ammonia attacks carbonyl makes tetrahedral intermediate and phosphate is released Hydroxide – not stable at neutral pH and not much of it, stable in abundance at pH 14 Need to have free pair of electrons, NH4+ would not have caused a nucleophilic attack Favors ammonium, but delta G drives the deprotonation of ammonium into ammonia Whole yellow background = know everything

Slide 34: - Ammonia level can rise and can replace glutamine in all of those reactions – save 1 molecule of ATP when you use ammonia in place of glutamine o Turns off glutamine synthetase when ammonia levels are high to save ATP - Enzyme will get shifted when there is a lot of ammonia around, but will get shifted back when there isn’t enough ammonia - Regulatory enzyme PII binds to the enzyme to inactive GS and adds AMP – PII binds phosphate to make active GS and creates ADP - High glutamine – ATP reaction - Low glutamine – UMP reaction

Slide 54:

- Tan cells are hepatocytes – man cells that make up liver - Red are parts of arterial circulation – epithelial cells - Portal vein is feeding in and hepatic artery are feeding in – common place that flow and enter central vein

Slide 56: - Low affinity – high capacity - High affinity – low capacity

Slide 57: - Arginine is made by the first steps in the urea cycle - Diet – arginine in proteins, digestion breaks down into AA

Slide 59: - Can make glutamate via transamination o Any AA besides the 4 mentioned from previous slides

Slide 61: - Solely by transamination of pyruvate - Serves as the basis of the alanine shuttle - Allows organs to transfer ammonia from one organ to another without it ever going into the bloodstream

Slide 62: - Electrophilic center and pair of electrons become cyclic amine that becomes reduced by NADH àproline

Slide 63: - Made in collagen – collagen is most abundant protein in the body - Mechanical strength by attaching to collagen

Slide 64: - Gray in box does not need to be memorized - We make glycine a number of different ways – do not need to be memorized - Collagen most abundant – every third AA is glycine, need a lot of glycine

Slide 65: - Conversion of phenylalinine to tyrosine - Reducing group built in (THB) – Phe reacts with enzyme with molecular oxygen, makes tyrosine and produced water + DHB 9/25/18 Slide 66 -

In the Western world there is a simple test for PKU, autosomal recessive disorder - take urine sample from patient when they are born - it will be high in phenylketonuria if they have PKU spray sample with solution of bacteria that allows cells to multiply and will cause a color change - If positive, doctors will put patient on a diet extremely low in phenylalanine - In adulthood, patients cannot eat much protein Individuals with PKU if left untreated will have sparse neural networks and won’t be able to think as clearly Slide 67 Cysteine is a conditionally essential amino acid All that cysteine needs from methionine is the sulfur - More methionine is found outside of proteins than within proteins - S-adenosyl-methionine (SAM) - CH2 is directly attached to sulfur with a positive charge - Use ATP, use all the energy of ATP to produce SAM so that the only part of ATP that ends up on the sulfur is SAM - S-adenosyl-homocysteine - can undergo hydrolysis to make the molecule homocysteine - Serine + homocysteine yields cystathionine - Cleave the bond between CH2 and S in order to produce cysteine Slide 68 Specialized amino acids...the synthesis of thyroxin (T4) - Has a related molecule triiodothyronine (T3) - 10x more active than T4 Not made from free amino acids but instead made from modifying a protein - thyroglobulin (6,000 AAs) - made and delivered to ER in thyroid cells where it is stored Iodide is actively transported to thyrocytes where it is oxidized to reactive iodine Iodination occurs via aromatic electrophilic substitution (ortho para directing) forming thyronine ring Tg is reabsorbed by cells and proteolyzed to form T4 Thyroglobulin (storage) releases T3 and T4 molecules Slide 69 Slide 70 We mainly make T4 and we store that in the thyrocyte as thyroglobulin Once it is released into our blood we have a little T3 and a lot of T4 Localize enzyme to convert T4 to T3 in the bloodstream at the tips of fingers and toes Once T3 is formed, it binds to mobile receptors and enter the cell to activate transcription factors T3 increases basal metabolic rate, O2 consumption, and the rate of ATP hydrolysis Slide 71 Some AAs are neurotransmitters -

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Glutamate - main excitatory neurotransmitter Aspartate D-Serine Glycine

*gray words we don’t need to know Slide 72 Glutamate is converted to gamma aminobutyrate D-serine formed by racemization by removing alpha hydrogen and putting it at different position Slide 73 Heme BIosynthesis - The enzymes for making heme are in mitochondria and cytosol compartments - It all starts with glycine reacting with succinyl-CoA to make ALA in the mitochondria which is then exported into the cytosol - In the last step iron is loaded into the group to make Heme Slide 74 Slide 84 Slide 85 Replace oxygen by nitrogen - first carry out isomerization to make OH and double bond, glutamine comes in and ammonia goes through tunnel - Phosphorylate oxygen to make it a good leaving group - Must come together to form amide linkage (close the ring) CAIR Look at substrate and look at product *(exam) - Add carboxyl group - nucleophilic attack on carboxyl phosphate intermediate - Make carbon carbon bond - start to see six membered ring develop Slide 86 - Want to put a nitrogen in position (ultimately want to leave as amino group) - Aspartic acid (amino succinic acid) - Activate carboxyl group to acyl phosphate then the amino group of aspartic acid (formation of SCAIR) Slide 87 Formyl group onto this nitrogen (in bacteria on the other nitrogen) - causes significant difference - Nitrogen attacks and causes water to be released - What drives the reaction is ring closure!!! ** the ring will be able to have aromaticity

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IMP - first fully formed nucleotide that organisms make

Slide 88 Get rid of oxygen replace with aspartic acid (use GTP not ATP) Why GTP? By having GTP, it helps to favor the formation of more ATP Low on guanine nucleotide - ATP facilitates reaction

Slide 90 - React with NAD and water and introduce oxygen - Activate oxygen as leaving group and replace with N Slide 93 Only 10% IMP forms XMP IMP stopped by feedback inhibition - IMP level has to reach a certain level Slide 96 - how purines are salvaged in our body Reusing parts of purine nucleotides to make new ones - Transfer phospho ribosyl group from PRPP to hypoxanthine to guanine - Adenine is NOT salvaged Slide 97 - purine degradation - Break ribose off guanosine - Bond between base and sugar has energy - nature wants to keep energy - so carries out phosphorolysis - phosphate breaks bond rather than oxygen...