Shared Flashcard Set

Details

Metabolism 62-69
Cederbaum (2 of 5)
90
Biochemistry
Graduate
08/09/2011

Additional Biochemistry Flashcards

 


 

Cards

Term
Fxn of aGP shuttle?
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
aGP & MA
Term
Fxn of MA shuttle?
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
Def of respiration.
Definition
1) flow of e- down respiratory chain, 2) reduction of O2 coupled to ATP synth
Term
Complex I
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
Complex III
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
Complex IV
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
Mech of ATP synthase.
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
What are Uncouplers?
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
Oligomycin, DCCD
Term
What tissues have glycogen stores?
Definition
Liver, muscle.
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
Functions of PPP.
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
G6PDH
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
Fxns of FAs (5).
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
4 regulators of B-oxdn?
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
liver
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
Fates of Palm CoA (4)?
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.
Supporting users have an ad free experience!