Bioenergetics & carbohydrate metabolism (L1,2) Flashcards
Where are ketone bodies produced and how?
In liver, occurs when FA’s are converted to acetylCoA faster than AcCoA can be oxidized thru TCA cycle
What is the 1st and 2nd law of thermodynamics?
1st: During any rxn, the total E of a system AND its surroundings remains constant:
ΔE= Q(heat absorbed) - W(work done)
2nd: A rxn always goes in direction to inc. total entropy of system AND surroundings:
ΔSsys + ΔSsurr >0
What is the equation for Gibbs free energy of a rxn?
ΔG= ΔGo + RTlnQ
ΔGo= -RTlnKeq = -1.36logKeq
What rxn is catalyzed by adenylate kinase?
ATP + AMP ⇔ 2ADP ΔGo=0
What AA’s are essentia for adults (meaning we need them in our diet)?
Ile, Leu, Lys, Met, His, Phe, Val, Thr, Trp
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What is the Basal Metabolic Rate? (BMR)
The energy expended at rest, can be measured by heat evolved.
NOTE: NOT the same as minimal E needed to sustain life
What is the net rxn for aerobic glycolysis and where does this occur?
Occurs in cytosol;
Glc+2ADP+2Pi+2NAD+→2pyr+2ATP+2NADH
ΔGo’= -20 kcal/mol
Hint: remember products and you’ll remember reactants
What are the 10 steps of Aerobic glycolysis and the enzymes that catalyze it?
1) Glc+ATP→Glc-6-P+ADP (G6P) [Hexokinase]
2) G6P→F6P [G6P isomerase]
3) F6P+ATP→F1,6bisP+ADP [6-PhosphoFructoKinase]
4) F1,6BP→DHAP+Glyceraldehyde3P [F1,6BP aldolase]
4. 5)DHAP→GA3P [Triosephosphate isomerase]
ALL SUBSEQUENT RXNS IS x2
5) GAP+NAD+Pi→1,3bisPhGlycerate [3PhGlyceraldehyde Dehydrogenase]
6) 1,3BPG+ADP→3PG+ATP [Phosphoglycerate kinase]
7) 3PG→2PG [Phosphoglycerate mutase]
8) 2PG→PEP+H2O [Enolase]
9) PEP+ADP→Pyr+ATP [pyr kinase]
How does the Glycerol 3 Phosphate shuttle work?
What organs does this occur in?
Skeletal muscle, and brain;
In cytosol, Glycerol 3 P DH oxidizes NADH→NAD+ while converting DHAP to Glycerol3P (G3P).
G3P→DHAP in Mitochochondrial IM by G3PDH, which couples FAD→FADH2 which reduces CoenzymeQ which enters oxidative phosphorylation.
How does the malate shuttle work and what organs is it in?
In heart, liver, kidney (HLK);
As OAA→Malate in cytosol, NADH→NAD+[Malate DH]
Then Malate is transported thru IMM to matrix via Malate transporter enzyme,
and Malate→OAA in matrix, NAD+→NADH.
What is the net rxn for anaerobic glycolysis?
Glc+2ADP+2Pi→2Lactate +2ATP
What is the step for pyruvate to become lactate?
Pyr + NADH→Lactate + NAD+ [Lactate DH]
NOTE: This is after 10 steps of glycolysis starting from Glc. Thus Total ATP yield is 4ATP, 2 net ATP.
What are the 3 thermodynamically irreversible rxns in glycolysis?
- Glc→G6P [Hexokinase]
- F6P→F1,6BP [Phosphofructokinase]
- PEP→Pyruvate [Pyruvate Kinase]
These are thermodynamically irreversible b/c ΔG’ is very negative.
What are the 4 allosteric effectors of Phosphofructokinase (PFK)?
F6P + ATP → F1,6-BP + ADP [PFK]
F6P + ATP → F1,6-BP + ADP [PFK]
- ATP: negative effector
- ADP: positive effector
- Citrate: negative effector
- Fructose-2,6-bisPhosphate: positive effector (note: glucagon dec F26BP, insulin inc. F26BP)
What allosteric effector affects Hexokinase?
Glc + ATP → G6P + ADP
G6P: negative effector
NOTE: When PFK slows, G6P and F6P accumulate, slowing Hexokinase
NOTE: In LIVER G6P does not affect this b/c glucokinase catalyzes this rxn not hexokinase
What are the 2 allosteric effectors of Pyruvate Kinase (PK)?
PEP + ADP → Pyruvate + ATP
PEP + ADP → Pyruvate + ATP [PK]
- ATP: negative effector
- F1,6BP: positive effector (note: As PFK rate inc., so does PK rate)
- RBCs lack___ meaning ___.
- Why can’t CNS utilize FAs?
- mitochondria meaning glycolysis is the sole pathway for energy generation, so lactate is the end product of energy metabolism
- B/c FA’s don’t cross blood/brain barrier, thus CNS uses Glc
What is the major/minor pathway for metabolism of Fructose in the liver?
An inherited deficiency in fructokinase and Aldolase B leads to what?
Major: 1)D-Fructose+ATP→F1P+ADP [Fructokinase]
2) F1P→Glycerald.+DHAP [Aldolase B]
3) Glyceraldehyde+ATP→GAP+ADP [triose kinase]
Minor: Fructose+ATP→F6P+ADP→glycolysis;
Deficiency in Fructokinase=essential fructosuria,
Deficiency in Aldolase B=fructose intolerance
What is the metabolic pathway for D-galactose?
An inherited deficiency in galactokinase and uridyltransferase leads to what?
1) Galactose+ATP→Gal1P+ADP [galactose kianse]
2) Gal1P→Glc1P [Gal1P uridyl transferase]
3) G1P→G6P [Phosphoglucomutase]
NOTE: Alternate pathway for Gal:
Gal+NADPH→Galactitol_NADP+ [Aldol reductase]
Deficiency in galactokinase=accumulation of galacitol
Deficiency in uridyltransferase=accum. of galactitol AND gal1P
What does the Pentose Phosphate Pathway (PPP) provide?
Provides NADPH, and ribose-5-P for synthesis of nucleic acids
- What is the net rxn for PPP?
- What are the 3 phases of the PPP and what happens in each?
1) 6 G6P +12 NADP+ → 4 F6P+ 2 GAP+ 6 CO2 + 12 NADPH
2) 1.Oxidation rxns: G6P+NADP→Ribulose5P+CO2+ 2NADPH
2. Isomerization rxns: Ribulose5P→Ribose5P
3. Rerrangement rxns: 3C5→2C6 +C3 (x2)
Transketolase transfers ___.
Transaldolase transfers___.
Show how it works in PPP.
Transketolase trnsfrs glycoaldehyde grp (C2)
Transaldolase trnsfrs DHAP grp (C3);
- C5+C5⇔C7+C3 [TK]
- C7+C3⇔C4+C6 [TA]
- C5+C4⇔C3+C6 [TK]
Thus: 3 ribulose5P⇔2 F6P+ GAP
Hint: TranskeTWOlase transfers TWO C’s and is used TWO times
- If requirement for NADPH exceeds requirement for pentoseP, excess __ is converted to __.
- If requirement for pentoseP exceeds rate of oxidation rxns, __ needs are met by conversion of __ to PentoseP by __.
- If pentoses are available in excess diet, they are converted to __ by __.
- PentoseP; glycolytic intermediates and metabolized
- PentoseP; F6P⪆ TA&TK
- Ribose5P, Ribulose5P, or xylulose5P and converted to F6P and GAP by TA and TK.
What rxn is catalyzed by methemoglobin reductase in RBCs?
MetHb(Fe3+) + NADH → Hb(Fe2+) + NAD+ [MetHb reductase]
The Hb can then catalyze superoxide from O2 by converting back to MetHb, which leads to:
superoxide +2H+ → H2O2 +O2 [superoxide mutase]
then:
2H2O2 → 2H2O + O2 [catalase]
What are the effects of pyruvate kinase deficiency?
- ATP lvls low in RBCs (not reticulocytes)
- Other glycolysis enzymes increased
- High 2,3BPG= dec. oxygen affinitiy for Hb
What are the effects of G6PDH deficiency? How is it treated?
What kind of chromosome disease is this?
Dec. stability of RBCs; Oxidative drugs (eg sulfa drugs, antibiotics) induce hemolysis of G6PDH deficient cells;
X-linked disease affecting >200million ppl