Term
|
Definition
| Get e- from NADH made in cyto (via glycolysis) into mito where it can enter respiratory chain. |
|
|
Term
| Which carriers does the aGP shuttle use? |
|
Definition
| None bc on outer surface of mito inner mbrne. |
|
|
Term
| Which shuttles are responsible for translocating the reducing equiv of NADH into the mito? |
|
Definition
|
|
Term
|
Definition
| Get NADH cyto-->mito; Get OAA (from pyruvate carboxylase rxn) mito-->cyto for gluconeogenesis. |
|
|
Term
| Which carriers are used in MA shuttle? |
|
Definition
4 to get malate in, aKG out.
7 to get glutamate in, aspartate out. |
|
|
Term
| How can we distinguish btwn MA & aGP shuttle? |
|
Definition
| MA produces NADH, aGP produces FADH2 |
|
|
Term
| Fxn of isocitrate shuttle? |
|
Definition
| NADPH (from PPP, transhydrogenase rxn) mito-->cyto (for biosynthetic rxns ie cholesterol synth, FA synth) |
|
|
Term
| What is the mitochondrial transhydrogenase rxn? |
|
Definition
Transfers Hs from NADH --> NADP+.
(NADH + NADP --> NAD+ NADPH) |
|
|
Term
| Which carriers are used in isocitrate shuttle? |
|
Definition
4 to get aKG in, malate out
3 to get malate in, isocitrate out |
|
|
Term
| What are inhibitors of the respiratory chain and what do they cause to build up? |
|
Definition
| CI-Rotenone(FeS accumulates), CIII-Antmycin A(QH2 accumulates, cyt c not reduced), CIV-cyanide, CO (reduced cyt c accumulates) |
|
|
Term
| What is Respiratory Control? |
|
Definition
| Oxidative Phosphorylation; Rate @ which e- flow (or O2 reduced to H2O) is regulated by the rate of ATP synthesis. |
|
|
Term
|
Definition
| 1) flow of e- down respiratory chain, 2) reduction of O2 coupled to ATP synth |
|
|
Term
|
Definition
| NADH dehydrogenase = NADH:Ubiquinone Reductase; NADH-->FMN-->FeS-->Q-->QH2; 4H+ pumped |
|
|
Term
| Complex II, name & e- pathway |
|
Definition
| Succinate Dehydrogenase = Succinate:Ubiquinone Reductase; Succinate-->FAD-->Q-->QH2 |
|
|
Term
|
Definition
| QH2 Cytochrome C Reductase = b:c1 complex; QH2-->cyt b(Fe3+)-->cyt b(Fe2+)-->FeS-->cyt c1-->cyt c(Fe3+)-->cyt c(Fe2+); 2 H+ pumped |
|
|
Term
|
Definition
| Cytochrome Oxidase = 2 Coppers + 2 Cytochromes; cyt c(Fe2+)-->CuA-->cyt c--> CuB-->cyt A3-->O2-->H2O; 4 H+ pumped |
|
|
Term
| What gradients compose the electromotive force? |
|
Definition
| 1) charge gradient, 2) pH gradient |
|
|
Term
|
Definition
| proton driven motor that 1) discharges bound ATP, 2) catalyzes phosphorylation of ADP+Pi-->ATP |
|
|
Term
| What fxns beside ATP synth utilize pmf (4)? |
|
Definition
1)Pumping "toxic" Ca2+ cyto-->mito,
2)Reverse e- transport,
3)transhydrogenase rxn which gets NADH into mito, 4)powering adenine nucleotide translocase which takes newly produced ATP mito-->cyto |
|
|
Term
|
Definition
| Allow protons to enter mito matrix destroying proton gradient necessary to capture energy as ATP. |
|
|
Term
| What 'ingredients' are necessary to produce pmf and ATP? |
|
Definition
| Mito, substrate, ADP, Pi, oxygen, NADH (via MA shuttle), FADH2 (via aGP shuttle) |
|
|
Term
| Inhibitors of ATP Synthase. |
|
Definition
|
|
Term
| What tissues have glycogen stores? |
|
Definition
|
|
Term
| Affect of low blood glucose on glycogen. |
|
Definition
Incr glu/epi --> 1)incr G6Pase txn in liver-->incr degradation of G6P-->G+Pi;
2)P-Phosphorylase Kinase--> P-Glycogen Phosphorylase (active);
3) P-Glycogen Synthase (inactive) |
|
|
Term
| Affect of high blood glucose on glycogen. |
|
Definition
| Incr insulin-->PP1 active --> de-P Glycogen Synthase (active) |
|
|
Term
| Role of Ca2+ in glycogen breakdown. |
|
Definition
| In muscle: epi-->incr Ca2+ --> activates Phosphorylase Kinase; under stress CNS releases Ca2+ to give some glycogen breakdown |
|
|
Term
| Role of metabolite control of glycogen metabolism? |
|
Definition
| Works mainly on "inactive" forms of enzymes to give a little activity before hormone signals start. Synthesis upreg by G6P, ATP. Degradation upreg by AMP. |
|
|
Term
| Enzymes that degrade glycogen to G1P. |
|
Definition
| Phosphorylase, debranching enzyme. |
|
|
Term
| Why is glycogen breakdown a phosphorolysis rather than hydrolysis? |
|
Definition
| Hydrolysis costs 1 ATP and gives glucose. Phosphorolysis gives G1P and saves the ATP. G1P and G6P stay in the cell better than glucose, which can leak out. |
|
|
Term
| Fates of G6P from glycogen breakdown in liver vs muscle? |
|
Definition
| Liver - maintains blood glucose conc --> to other tissues. Muscle - fuel reserve for synth of ATP during muscle contraction. |
|
|
Term
| Why does G6P from glycogen enter glycolysis in muscle but not liver? |
|
Definition
| G6Phosphatase is in liver only, converts G6P-->G1P which leaves hepatocytes bc glucokinase low affinity for glucose. In muscle G6P enters glycolysis bc trapped in cell. |
|
|
Term
| What hormone stimulates glycogen breakdown in muscle vs liver? |
|
Definition
| Muscle-Epi, Liver-Epi/Glu. |
|
|
Term
| If Epi/Glu decr F26bisP (blocking glycolysis and increasing G6Pase) how does G6P enter glycolysis in muscle? |
|
Definition
| F26bisP kinase and phosphatase in muscle are diff isoforms than in liver and show opposite P/de-P responses. |
|
|
Term
| Effect of epi in liver vs muscle insofar as glycogen. |
|
Definition
Liver - P decr kinase activity/incr phosphatase activity-->decr F26visP-->decr glycolysis (so glucose sent out rather than metabolized).
Muscle - P incr kinase activity/decr phosphatase activity-->incr F26bis P-->incr glycolysis |
|
|
Term
|
Definition
| 1) Produce NADPH - crucial for cholesterol/FA synth, reducing oxidative stress; 2) Produce ribose-5-P |
|
|
Term
| How does a TPP def affect RBCs? |
|
Definition
| Unable to protect from oxidant damage (decr NADPH-->decr ability to reduce GSSG back to GSH) --> hemolytic anemia. |
|
|
Term
| Why does a TPP def not cause as much damage to cells w mito as it does to cells without? |
|
Definition
| Cells w mito can use isocitrate shuttle to synth NADPH. |
|
|
Term
| In what tissues does the PPP have high activity vs low activity? |
|
Definition
| High in rapidly dividing/synthetic tissue ie liver, adipose, mammary, adrenals, RBC. Low in brain, heart, muscle. |
|
|
Term
| How is H2O2 removed from RBCs? |
|
Definition
| 1) Catalase decomposes H2O2 --> O2+H2O. 2)Glutathione Peroxidase uses glutathione (GSH) to catalyze H2O2 + 2GSH --> 2 H2O + GSSG (= rdxn of H2O2) |
|
|
Term
| How is GSH reoxidized from GSSG? |
|
Definition
| GSSG + 2 NADPH --> 2 GSH + 2 NADP+ (by glutathione reductase) |
|
|
Term
| What enzyme is often deficient in the PPP? |
|
Definition
|
|
Term
| Rate limiting step of PPP, how is it regulated? |
|
Definition
| 1st step: G6P-->6 phosphogluconic acid (by G6PDH); inhib by high NADPH:NADP+ ratio; stim by low ratio, insulin incr G6PDH gene expression. |
|
|
Term
| Gluconeogenesis occurs in which tissues and where in cell? |
|
Definition
| Liver (a little in kidney), mito-->cyto |
|
|
Term
| Co-factor reqd for gluconeogenesis? |
|
Definition
| Biotin for Pyruvate Carboxylase. |
|
|
Term
| What are the substrates for synthesizing glucose? |
|
Definition
| Lactate, pyruvate, glucogenic AAs, (lesser) glycerol from breakdown of triglycerides. |
|
|
Term
| How does pyruvate get directed to gluconeogenesis rather than Krebs (2 ways)? |
|
Definition
1)Glu incr txn of Pyruvate Carboxylase which is stim by AcCoA (Pyruvate+ATP-->OAA+ADP);
2)PDH (Pyruvate-->AcCoA) is inhib by AcCoA and the same high energy conditions that stim PC. |
|
|
Term
| Can FAs be a precursor for glucose? Explain. |
|
Definition
| No, AcCoA cannot --> Pyruvate bc PDH (Pyruvate-->AcCoA) rxn is irreversible. |
|
|
Term
| What are the irreversible steps of glycolysis that have to be overcome by gluconeogenesis? |
|
Definition
Pyruvate Kinase (PEP-->Pyruvate)
PFK1 (F6P-->F16P)
Hexokinase/glucokinase (Glucose-->G6P) |
|
|
Term
| Last step of gluconeogenesis and where does it occur? |
|
Definition
| G6P-->Glucose (via G6Phosphatase), in ER |
|
|
Term
| How is Pyruvate Kinase step reversed in gluconeogenesis and what prevents futile cycle? |
|
Definition
| Pyruvate+ATP-->OAA+ADP (via Pyruvate Carboxylase), OAA+GTP-->PEP+GDP (via PEPCK); Glu incr PEPCK/PC but inhib PK, high vs low energy signals. |
|
|
Term
| How is PFK step reversed in gluconeogenesis and what prevents futile cycle? |
|
Definition
F16bisP-->F6P+Pi via F16bisPhosphatase;
Glu incr F16bPhosphatase but inhib PFK via F26bP cycle, insulin does opp;
ATP, citrate stim F16bP, inhib PFK. |
|
|
Term
| How is gluco/hexokinase step reversed in gluconeogenesis and what prevents futile cycle? |
|
Definition
| G6P-->Glucose via G6Phophatase; Glu incr txn of G6Pase but inhib glucokinase. |
|
|
Term
| What mobilizes the breakdown of triglycerides? |
|
Definition
| Hormone Sensitive Lipase (activated by glu/epi) hydrolyzes triglycerides to glycerol + FAs. |
|
|
Term
| Where in cell does PEPCK rxn occur? |
|
Definition
| Can occur in mito or cyto. If in mito PEP exits via carrier 3. If in cyto OAA exits mito as Malate via carrier 2,3,4 and is converted back to OAA via MDH (=MA shuttle). |
|
|
Term
| What role do FAs play in gluconeogenesis? |
|
Definition
| B-oxdn of FAs produces AcCoA --> stim Pyruvate Caroxylase / inhib Pyruvate Kinase. |
|
|
Term
| Fate of glycerol from triglyceride hydrolysis? |
|
Definition
| Glycerol+ATP-->G3P+ADP via glycerol kinase; G3P can join gluconeogenesis or glycolysis. |
|
|
Term
|
Definition
| 1)Membrane component, 2) energy source, 3) energy storage as triglycerides, 4) signal transduction molecules, 5) produce prostoglandins, leukotrienes |
|
|
Term
| Why can brain not oxidize FAs for energy? |
|
Definition
| FA-albumin complex cannot cross BBB. |
|
|
Term
| What does each step of B-oxdn produce? |
|
Definition
| 1 AcCoA, 1 NADH, 1 FADH2. |
|
|
Term
| What are the final products of odd chain FA breakdown? |
|
Definition
| AcCoAs + propionyl CoA; Propionyl CoA --> Succinyl CoA (req B12) --> Heme synth or TCA/gluconeogenesis. |
|
|
Term
| How does fatty acyl CoA get into mito? |
|
Definition
| Via Carnitine Shuttle (carnitine translocase carrier)as fatty acyl carnitine; conversions catalyzed by CPT1&2. |
|
|
Term
| What is the yield of ATP from B-oxdn? |
|
Definition
| (# of Cs - 2)/2 NADHs, same # of FADH2s. NADH=2.5ATP, FADH2=1.5ATP. |
|
|
Term
| What is the ketogenesis pathway? |
|
Definition
| 3 step pathway via which 2 AcCoAs --> acetoacetate, which can then --> acetone+CO2 or B-hydroxybutyrate. |
|
|
Term
| Why would AcCoA enter ketogenesis rather than Krebs cycle in liver mito? In what situation does this occur? |
|
Definition
| If not enough OAA. Occurs in fasting state when rush of FA breakdown floods liver w AcCoA which inhibits PDH but stim PC which converts pyruavte to OAA and uses it for ketogenesis. |
|
|
Term
| Can FA oxdn provide glucose? |
|
Definition
| Only odd chain FAs bc --> propionyl CoA --> succinyl CoA. |
|
|
Term
| Can the brain use ketone bodies for fuel? |
|
Definition
| Only in extended starvation conditions, when the transferase enzyme is induced. |
|
|
Term
|
Definition
| 1)Availability of FAs via activated hormone sensitive lipase, 2)Availability of carnitine, 3)Malonyl CoA inhibits carnitine acyl transferases, 4)Rate of e- transport chain. |
|
|
Term
| What is an inborn error of metabolism in B-oxdn? |
|
Definition
| Inability to synth carnitine from lysine. |
|
|
Term
| Who is at risk for ketosis? |
|
Definition
| Diabetics, poorly nourished alcoholics. |
|
|
Term
| How do ketone bodies leave where they are synth and where do they go? |
|
Definition
| Exit mito on carrier 5, liver-->blood-->tissues-->AcCoA-->Krebs. |
|
|
Term
| What is first step pf b-oxdn? |
|
Definition
| Activation of FA-->fatty acyl CoA via FA activating enzyme. |
|
|
Term
| What are the 2 potential carnitine deficiencies and what is effect of each? |
|
Definition
| Both decr ability to use LCFAs as fuel. CPT-I def-->inability of liver to use LCFA as fuel-->hypoglycemia/coma/death. CPT-II def-->effects cardiac/skeletal muscle--> cardiomyopathy, muscle weakness, etc; treat w high carb/low LCFA diet, supplement w MCFAs/carnitine. |
|
|
Term
| What tissue cannot use ketone bodies as fuel in any conditoin? |
|
Definition
|
|
Term
| Why would citrate enter FA synth rather than continue thru Krebs? |
|
Definition
| ATP, which is produced by Krebs and needed for FA synth, inhibits Krebs causing citrate to accumulate and leave mito via carrier 3. |
|
|
Term
| Rate limiting step of FA Synth and how is it regulated? |
|
Definition
| Acetyl CoA Carboxylase (AcCoA-->Malonyl CoA); reqs ATP, inhib by PalmCoA/AMP/Glu, stim by Citrate/insulin. |
|
|
Term
| Role of malonoyl CoA in FA synth (2)? |
|
Definition
1)AcCoA carboxylase adds CO2 to AcCoA to make malonoyl CoA which then condenses w AcCoA (via FAS) to eventually form Palm CoA;
2)Malonoyl CoA prevents futile cycling by inhib CPT so FA can't get into mito where they'd be b-oxidized. |
|
|
Term
| How is a futile cycle btwn FA synth and breakdown prevented? (4 ways) |
|
Definition
1)Malonoyl CoA inhibition of CPT,
2)AcCoA from b-oxdn cant leave mito-->cyto where FA synth occurs,
3)Insulin dePs-->inactivates HSL,
4)Insulin dePs-->inactivates AcCoA Carboxylase. |
|
|
Term
| How would mutation of insulin receptor affect FA synth? |
|
Definition
| 1)SREBP wouldnt be activated, therefore FA biosynthetic enzyme txn would not be upregulated; 2)insulin wouldnt deP/activate AcCoA Carboxylase. |
|
|
Term
| Role of tricarboxylic acid carrier (carrier 3) on FA synth? |
|
Definition
Citrate uses to leave mito and enter lipogenesis
|
|
|
Term
| Under what condition are FAs synth? |
|
Definition
| High glucose & AA levels. |
|
|
Term
| Where are FAs synth and where do they go? |
|
Definition
| Cyto of most cells but esp liver --> adipose tissue as trigycerides packaged as VLDL. |
|
|
Term
| What does citrate shuttle do in FA synth? |
|
Definition
| In mito, citrate (from AcCoA+OAA) leaves -->cyto via tricarboxylic acid carrier (3). In cyto is cleaved by citrate lyase to OAA+AcCoA. OAA is a)reduced to malate which re-enters mito or b)oxidized in cyto by malic enzyme to pyruvate+NADPH, pyruvate enters mito-->OAA via pyruvate carboxylase. |
|
|
Term
| What co-factor is needed for rate limiting step of FA synth? |
|
Definition
| Biotin reqd for AcCoA+CO2-->Malonyl CoA via AcCoA Carboxylase. |
|
|
Term
| Where does NADPH for FA synth come from? |
|
Definition
| 1)PPP, 2)Malic enzyme, 3)Transhydrogenase rxn + isocitrate shuttle |
|
|
Term
| What enzyme(s) condense AcCoA + repeating malonoyl CoAs to make Palm CoA? |
|
Definition
| Fatty Acyl Synthase (FAS) complex = Acyl Carrier Protein (ACP) + Condensing enzyme. |
|
|
Term
| What are the 5 basic steps of FAS? |
|
Definition
| 1) Transfer of Malonoyl grp, 2)Condensation, 3)Reduction, 4)Dehydration, 5)Reduction. |
|
|
Term
| How many AcCoA, NADPH, ATP are needed to form Palm CoA? |
|
Definition
| 8 AcCoA, 14 NADPH, 7 ATP. |
|
|
Term
|
Definition
| 1)Stored as triglycerides, 2)Forms phospholipids for mbrnes, 3)Can be elongated to C18-C20 FAs via FA elongation in liver ER/mito, 4)Can be desat to unsat FAs. |
|
|
Term
| What enzymes are activated under lipogenic conditions (4) and how? |
|
Definition
| 1)AcCoA Carboxylase, 2)FA Synthase, 3)Citrate Lyase, 4)Malic enzyme. Transcriptionally upregulated by SREBP which is activated by insulin, inactivated by glu/epi. |
|
|
Term
| How does AcCoA from pyruvate get out of mito to enter FA synth? |
|
Definition
| In mito - combines w OAA to form citrate which --> cyto where OAA comes off leaving AcCoA. |
|
|
