METAB 1 EXAM 2 STUDY GUIDESUMMER 2013TCA Cycle (Krebs Cycle; Citric Acid Cycle)a. Know various names for this cycle. b. Recognize and be able to give examples of this cycle's role as a common metabolic pathway (e.g. where can its intermediaries originate? What can they be diverted from the cycle and used for?)c. Proteins are cleaved into AAs, which can then be transaminated to form pyruvate OR if they’re ketogenic, can form ketone bodies that can be oxidized to make acetyl-CoAd. Carbohydrates are metabolized as glucose, which goes through glycolysis to form pyruvatee. Lipids are broken down into fatty acids, which can then undergo beta-oxidation to form acetyl-CoAf. Citrate can be used in the synthesis of fatty acidsg. Alpha-ketoglutarate can be used to synthesize glutamate (through transamination)h. Succinyl-CoA can be part of the heme portion of some moleculesi. OAA can be transaminated into aspartate, and then used to form pyrimidinesj. OAA can also be converted into glucosek. Know reactions, enzymes, energetics, etc. l.Molecules MnemonicCitrate Cancis-Aconitate (intermediate) AdamIsocitrate Intriguealpha-Ketoglutarate ASuccinyl~CoA SuperSuccinate SexyFumarate FoxyMalate MamaOxaloacetate (OAA) Okay!Enzymes Mnemonic Coenzymes Energetics(citrate) Synthase So (gives off CoASH)Aconitase At dehydration (-H2O)Aconitase Another hydration (+H2O)(isocitrate) DehydrogenaseDance, NAD+ (gives off CO2) NADH+H+ (3 ATPs)( -αketoglutarate)Dehydrogenase complexDevon like PDH complex: TPP, FAD, NAD, CoASH, lipoate (gives off CO2)NADH+H+ (3 ATPs)(succinic) Thiokinase Took GDP (gives off CoASH) GTP (1 ATP) *used to convert OAA-->PEP in gluconeogenesis(succinate) DehydrogenaseDown FAD FADH2 (2 ATPs)Fumarase Five hydration (+H2O)Enzymes Mnemonic Coenzymes Energetics(malate) DehydrogenaseDrinks NAD NADH+H+ (3 ATPs)TOTAL: 12 ATPs/ molecule of Acetyl-CoARED- rate-controlling enzymesYELLOW- ATP formationLiver, kidneys, cardiac muscle: produce 38 ATPs because they have the malate shuttle that uses the NADH+H+ to form NAD (3 ATPs formed)Skeletal muscle and brain: produce 36 ATPs because they use the glycerol-3-phosphate shuttle that uses FAD to form FADH (only 2 ATPs formed)m.Identify example of substrate level phosphorylation. n. - Succinyl~CoA-->Succinate o. (enzyme= succinic thiokinase)p. - kinase+high energy compound= production of ATP (GTP=ATP)q. - in this case, uses GDP-->GTPr. Describe the role of OAA in regulating cycle activity. s. Discuss the role of NADH and ATP in controlling TCA cycle activities. t. End-product inhibition: u. NADH+H+ inhibits all dehydrogenases (because they are the by-products)v. ATP inhibits citrate synthase (first step in cycle; because we don’t need to generate reduced coenzymes to be sent to the ETC to make more ATP) and isocitrate dehydrogenase (ONLY ONE!)w. Citrate blocks citrate synthase (because citrate is already formed)x. Succinyl-CoA inhibits alpha-ketoglutarate dehydrogenase (enzyme prior; because it is already formed) and citrate synthasey.z. Electron transport chain (ETC) a. State the purpose and cellular location and list the components of the ETC.Purpose: to form ATP (energy) by coupling the processes of oxidation and phosphorylation. The coenzymes previously reduced in the TCA cycle, etc. are being re-oxidized and ADP is being phosphorylated to ATP.Cellular Location: inner mitochondrial membrane (TCA Cycle happens in the matrix)Components: 4 proton pump complexes embedded in the membrane: I (NADH dehydrogenase complex): pumps 4 protons; where NADH+H+ startsII (Succinate Q reductase): does NOT pump any protons; where FADH2 startsIII (Cytochrome B-C complex): pumps 4 protonsIV (Cytochrome oxidase complex): pumps 2 protons ONLY because 2 are going to be used to form water by reducing 1/2 O2ATP Synthase (complex V): F0: allows for the translocation of protons; rotates and changes conformation of the complex to allow for phosphorylation of ADPF1: catalytic part that contains binding sites for ADP and inorganic phosphate2 mobile electron transporter complexes:Ubiquinone/coenzyme Q - transports pairs of electrons between complex I to III or II to IIICytochrome C - transports pairs of electrons between III and IVb. Discuss how ATP is synthesized via oxidative phosphorylation.The pumping of protons (4 for every pair of electrons from NADH+H+ and FADH2) out into the intermembrane space of the mitochondria causes an energy gradient. This gradient allows for the passive diffusion of protons back out through the ATP synthase complex into the matrix. F0 starts rotating and allows the protons to flow back in through F1 by changing the conformation of the complex. This return flow of protons furnishes the energy necessary for the synthesis of ATP from ADP and inorganic phosphate in the matrix and is catalyzed in the F1 part of the enzyme.c. State why the maximum theoretical yield of ATPs for electrons introduced into the ETC via NADH + H+ is 3, whereas for electrons introduced via FADH2 is 2.When you start the ETC with 2 NADH+H+, you start at complex I and pump a total of 10 protons (H+) out.When you start the ETC with 2 FADH2, you start at complex II and only pump a total of 6 protons (H+) out.Therefore, the energy gradient will be larger when using NADH+H+ and will produce more ATP due to more protons being brought back in through ATP synthase.Fructose and galactose metabolism a. Why are fructose and galactose metabolized primarily in the liver? Hexokinase can phosphorylate any hexose and is present in all cells in the body, including the liver, but it is rare for it to phosphorylate fructose/galactose because hexokinase is saturated at all times with glucose (has a lower Km for glucose, therefore higher affinity). Hexokinase has a higher Km (lower affinity) for fructose and galactose when compared to glucose.Therefore, the liver has specific enzymes (fructokinase and galactokinase) to phosphorylate fructose and galactose at the start of their metabolism.b. Discuss how ingestion of large amounts of fructose may have detrimental metabolic consequences. Fructose enters glycolysis (as a triose phosphate, glyceraldehyde-3-phosphate) AFTER the rate-controlling step that includes PFK-1. Therefore, if we ingest fructose, there is no rate control of its conversion to pyruvate. This pyruvate can be converted to acetyl-CoA, which then increases the synthesis of FA in the liver, and then these FA can be incorporated into triglycerides. DHAP can also be
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