Bioenergetics & carbohydrate metabolism (L1,2)

Question 1

Where are ketone bodies produced and how?

Answer 1

In liver, occurs when FA’s are converted to acetylCoA faster than AcCoA can be oxidized thru TCA cycle

Question 2

What is the 1st and 2nd law of thermodynamics?

Answer 2

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:

ΔS_sys + ΔS_surr >0

Question 3

What is the equation for Gibbs free energy of a rxn?

Answer 3

ΔG= ΔG^o + RTlnQ

ΔG^o= -RTlnKeq = -1.36logK_eq

Question 4

What rxn is catalyzed by adenylate kinase?

Answer 4

ATP + AMP ⇔ 2ADP ΔG^o=0

Question 5

What AA’s are essentia for adults (meaning we need them in our diet)?

Answer 5

Ile, Leu, Lys, Met, His, Phe, Val, Thr, Trp

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Question 6

What is the Basal Metabolic Rate? (BMR)

Answer 6

The energy expended at rest, can be measured by heat evolved.

NOTE: NOT the same as minimal E needed to sustain life

Question 7

What is the net rxn for aerobic glycolysis and where does this occur?

Answer 7

Occurs in cytosol;

Glc+2ADP+2P_i+2NAD⁺→2pyr+2ATP+2NADH

ΔG^o’= -20 kcal/mol

Hint: remember products and you’ll remember reactants

Question 8

What are the 10 steps of Aerobic glycolysis and the enzymes that catalyze it?

Answer 8

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]

Question 9

How does the Glycerol 3 Phosphate shuttle work?

What organs does this occur in?

Answer 9

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.

Question 10

How does the malate shuttle work and what organs is it in?

Answer 10

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.

Question 11

What is the net rxn for anaerobic glycolysis?

Answer 11

Glc+2ADP+2Pi→2Lactate +2ATP

Question 12

What is the step for pyruvate to become lactate?

Answer 12

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.

Question 13

What are the 3 thermodynamically irreversible rxns in glycolysis?

Answer 13

1. Glc→G6P [Hexokinase]
2. F6P→F1,6BP [Phosphofructokinase]
3. PEP→Pyruvate [Pyruvate Kinase]

These are thermodynamically irreversible b/c ΔG’ is very negative.

Question 14

What are the 4 allosteric effectors of Phosphofructokinase (PFK)?

F6P + ATP → F1,6-BP + ADP [PFK]

Answer 14

F6P + ATP → F1,6-BP + ADP [PFK]

1. ATP: negative effector
2. ADP: positive effector
3. Citrate: negative effector
4. Fructose-2,6-bisPhosphate: positive effector (note: glucagon dec F26BP, insulin inc. F26BP)

Question 15

What allosteric effector affects Hexokinase?

Glc + ATP → G6P + ADP

Answer 15

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

Question 16

What are the 2 allosteric effectors of Pyruvate Kinase (PK)?

PEP + ADP → Pyruvate + ATP

Answer 16

PEP + ADP → Pyruvate + ATP [PK]

1. ATP: negative effector
2. F1,6BP: positive effector (note: As PFK rate inc., so does PK rate)

Question 17

1. RBCs lack___ meaning ___.
2. Why can’t CNS utilize FAs?

Answer 17

1. mitochondria meaning glycolysis is the sole pathway for energy generation, so lactate is the end product of energy metabolism
2. B/c FA’s don’t cross blood/brain barrier, thus CNS uses Glc

Question 18

What is the major/minor pathway for metabolism of Fructose in the liver?

An inherited deficiency in fructokinase and Aldolase B leads to what?

Answer 18

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

Question 19

What is the metabolic pathway for D-galactose?

An inherited deficiency in galactokinase and uridyltransferase leads to what?

Answer 19

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

Question 20

What does the Pentose Phosphate Pathway (PPP) provide?

Answer 20

Provides NADPH, and ribose-5-P for synthesis of nucleic acids

Question 21

1. What is the net rxn for PPP?
2. What are the 3 phases of the PPP and what happens in each?

Answer 21

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)

Question 22

Transketolase transfers ___.

Transaldolase transfers___.

Show how it works in PPP.

Answer 22

Transketolase trnsfrs glycoaldehyde grp (C₂)

Transaldolase trnsfrs DHAP grp (C₃);

1. C₅+C₅⇔C₇+C₃ [TK]
2. C₇+C₃⇔C₄+C₆ [TA]
3. C₅+C₄⇔C₃+C₆ [TK]

Thus: 3 ribulose5P⇔2 F6P+ GAP

Hint: TranskeTWOlase transfers TWO C’s and is used TWO times

Question 23

1. If requirement for NADPH exceeds requirement for pentoseP, excess __ is converted to __.
2. If requirement for pentoseP exceeds rate of oxidation rxns, __ needs are met by conversion of __ to PentoseP by __.
3. If pentoses are available in excess diet, they are converted to __ by __.

Answer 23

1. PentoseP; glycolytic intermediates and metabolized
2. PentoseP; F6P⪆ TA&TK
3. Ribose5P, Ribulose5P, or xylulose5P and converted to F6P and GAP by TA and TK.

Question 24

What rxn is catalyzed by methemoglobin reductase in RBCs?

Answer 24

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]

Question 25

What are the effects of pyruvate kinase deficiency?

Answer 25

1. ATP lvls low in RBCs (not reticulocytes)
2. Other glycolysis enzymes increased
3. High 2,3BPG= dec. oxygen affinitiy for Hb

Question 26

What are the effects of G6PDH deficiency? How is it treated?

What kind of chromosome disease is this?

Answer 26

Dec. stability of RBCs; Oxidative drugs (eg sulfa drugs, antibiotics) induce hemolysis of G6PDH deficient cells;

X-linked disease affecting >200million ppl