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7. ELECTRON TRANSPORT CHAIN (PART 2)

Electron Transport chain: Different Substrate Shuttle Systems Medical Editor: Jona Frondoso

OUTLINE (ii) Transport of malate into the mitochondrial

matrix
I) INTRODUCTION
II) SUBSTRATE SHUTTLE SYSTEMS Malate can cross the mitochondrial membrane and
III) APPENDIX it passes through as aspartate is coming out.
IV) REVIEW QUESTIONS
V) REFRENCES
(2) Regeneration of NADH and Oxaloacetate in the
Mitochondrial Matrix (Figure 1)
I) INTRODUCTION
Malate is pushed into the mitochondrial matrix.
(1) Glycolysis Electrons from malate are being pulled off by a
Occurs in the cytoplasm mitochondrial malate dehydrogenase
Generates 2 NADH per glucose molecule Malate is reoxidized back to OAA
NAD is converted to NADH
NADH can now react with Complex I
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(2) NADH o NADH transfers the reducing equivalents via Complex
Must be able to unload its electrons onto the electron I to reach the final acceptor
transport chain
Unable to cross the mitochondrial membrane (3) Formation and Transport of Aspartate (Figure 1)
Cytosolic NADH has to disguise themselves in a different
way to be able to enter the mitochondria (i) Formation of Aspartate
Oxaloacetate must be transported back into the
Remember:
cytosol for the shuttle to continue.
Oxidative Phosphorylation OAA combines with glutamate
o Glutamate transfers an amine group onto the
NADH and FADH2 donate electrons to → ETC leads to → OAA forming aspartate
Electron flow coupled with → Transport of H+ from → The o Glutamate with an amine group forms alpha-
matrix to the IMS creating → An electrical and a pH gradient ketoglutarate
across → The inner mitochondrial membrane generating → o Catalyzed by mitochondrial aspartate
Sufficient energy to drive ATP synthesis transaminase

(ii) Transport of aspartate into the cytoplasm

II) SUBSTRATE SHUTTLE SYSTEMS Aspartate moves out through the malate-aspartate
shuttle into the cytoplasm
(A) MALATE-ASPARTATE SHUTTLE

(4) Regeneration of Glutamate and Oxaloacetate in the

Cytoplasm (Figure 1)
Aspartate in the IMS reacts with alpha-ketoglutarate
o Aspartate transfers its amine group to alpha-
ketoglutarate regenerating glutamate.
o Glutamate which also gets pumped back in
o Aspartate is reconverted back into OAA
o Catalyzed by cytosolic aspartate aminotransferase
OAA can now react with NADH to produce malate.
o To keep pulling hydride ions from NADH and take
these electrons into the ETC

Remember:
Aspartate (D) and Glutamate (E)
Figure 1. The Malate-aspartate shuttle system carries NADH
electrons into the mitochondrial matrix. [Nelson &Cox, 2017] Ionized forms of the amino acids aspartic acid and glutamic
acid respectively
Amino acids has a carboxyl group and an amino group
(1) Formation and Transport of Malate (Figure 1)
Remember:
(i) Formation of Malate
“MAD” Commute
NADH from glycolysis drops off 2 electrons onto
oxaloacetate (OAA) M - Malate going in
NADH from glycolysis is converted to NAD+ A - Alpha-ketoglutarate
Oxaloacetate is converted to malate D – Aspartate going out
Catalyzed by cytosolic malate dehydrogenase

ELECTRON TRANSPORT CHAIN (PART 2) METABOLISM: Note #7. 1 of 3

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(B) GLYCEROPHOSPHATE SHUTTLE Remember:

Table 1. Summary of the Malate-Aspartate and Glycerophosphate

Shuttle Systems
Shuttle Malate-
Glycerophosphate
System Aspartate
Two electrons NADH to OAA
NADH to DHAP
transferred
Cytosolic Cytosolic glyceral-3-
Through malate phosphate
dehydrogenase dehydrogenase
Product Malate Glyceral-3-phosphate
Mitochondrial
Glyceral-3-phosphate
Oxidized by malate
dehydrogenase
dehydrogenase
Oxidized as NAD+ FAD

(C) BETA-OXIDATION
(1) Cytoplasmic Reaction (Figure 3)
Figure 2. The Glycerol-3-phosphate shuttle carries NADH In beta-oxidation or breakdown of fatty acids, in order for
electrons into the mitochondrial matrix. [Nelson &Cox, 2017]
the fatty acids to be transported into the mitochondrial
matrix, it has to have a CoA attached to it
(1) Cytoplasmic Reactions (Figure 2)
Dihydroxyacetone phosphate (DHAP) gains hydride (2) Mitochondrial Matrix Reactions (Figure 3)
ions from NADH forming glyceral-3-phsophate and NAD+
Fatty acyl-CoA can also reduce FAD to FADH2
Glyceral-3-phosphate has a specific channel into the
FAD oxidizes fatty acyl-CoA to enoyl-CoA
mitochondrial matrix.
Catalyzed by acyl CoA dehydrogenase
Generated FADH2 can react to Complex 2
(2) Mitochondrial Matrix Reactions (Figure 2) Generated FADH2 can also transport electrons via
Complex II to the next component coenzyme Q until final
Glcyceral-3-phosphate reduced FAD to FADH2.
acceptors are reached.
Meanwhile FAD oxidizes glyceral-3-phsophate back to
DHAP
Catalyzed by glyceral-3-phosphate dehydrogenase
Generated FADH2 can react with Complex II
FADH2 transport electrons via Complex II to the next
component coenzyme Q until final acceptors are reached.

Figure 3. Oxidation of a fatty-acyl CoA to enoyl-CoA generates

FADH2. [Nelson &Cox, 2017

III) APPENDIX

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Figure 4. Malate-aspartate Shuttle System, Glycerophosphate Shuttle System, and Beta-Oxidation

2 of 3 METABOLISM: Note #7. ELECTRON TRANSPORT CHAIN (PART 2)

 IV) REVIEW QUESTIONS
Substrate shuttle system which regenerates NADH
in the mitochondrial matrix
a. Malate-aspartate
b. Glycerophosphate
c. Fatty-acyl CoA
d. Krebs Cycle

Which of the following statements is correct?

a. The electrons are transferred from NADH to
oxaloacetate in the malate-aspartate shuttle
b. Conversion of FADH2 to DHAP is catalyzed by
cytosolic glycerol-3-phosphate dehydrogenase.
c. FAD reduces fatty-acyl CoA to enoyl CoA
d. Fatty acids can freely enter the mitochondrial matrix.

In the malate-aspartate shuttle, glutamate transfers

a/an _______ group to form aspartate.
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a. carboxyl
b. amino
c. ester
d. hydroxyl

Which of the following reactions take place in the

mitochondrial matrix?
a. Formation of malate
b. Formation of glyceral-3-phasphate
c. Oxidation of NADH
d. Reaction catalyzed by acyl CoA dehydrogenase

CHECK YOUR ANSWERS

V) REFRENCES

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Nelson, D., & Cox, M. (2017). Lehninger Principles of
Biochemistry (7th ed.). New York: W.H Freeman and Company.

ELECTRON TRANSPORT CHAIN (PART 2) METABOLISM: Note #7. 3 of 3