Biochemistry

2.08A PYRUVATE DEHYDROGENASE COMPLEX &

TRICARBOXYLIC ACID CYCLE COMPLEX
Dr. Maria Lilia T. Reyes | October 11, 2018
LE 2
OUTLINE II. Pyruvate Dehydrogenase (PDH) Reaction
I. Objectives C. Energetics of the TCA
II. Pyruvate Dehydrogenase D. Summary of Krebs
Complex Reaction (PDH) Cycle
A. Pyruvate E. Fates of Carbon
Dehydrogenase (E1) Atoms in Krebs Cycle
B. Dihydrolipoyl F. Catabolism of the
Transacetylase (E2) Major Nutrients
C. Dihydrolipoyl G. Role of Vitamins in
Dehydrogenase (E3) Krebs Cycle
III. Tricarboxylic Acid Cycle H. Amphibolic Nature of
(TCA) CAC
A. Introduction I. Anaplerotic Reactions
B. Reactions of the TCA of TCA
cycle J. Regulation of Krebs
1. Synthesis of Citrate Cycle
from Acetyl CoA and K. Clinical Correlations Figure 1. General Scheme of Oxidative Decarboxylation of Pyruvate
Oxaloacetate 1. Beri-Beri (Dr. Reyes’ ppt)
2. Isomerization of 2. Genetic
• PDH reaction is the reaction that links glycolysis to TCA cycle
Citrate to Isocitrate Disorders of CAC
3. Oxidation and L. ATP Yield • The pyruvate dehydrogenase complex is analogous to α-
ketoglutarate dehydrogenase complex of the citric acid cycle
Decarboxylation of M. Shuttle Mechanisms
Isocitrate for Cytoplasmic • Pyruvate utilizes Pyruvate translocase with the aid of the
4. Oxidation and Reducing Equivalents Hydride ion (H-) to traverse the mitochondria.
Decarboxylation of α- IV. Review Questions Recall that pyruvate is the end-product of glycolysis (a
ketoglutarate V. References cytosolic reaction)
5. Cleavage of Succinyl • Deficiency in pyruvate dehydrogenase will result into
CoA Congenital Lactic acidosis (an inborn error)
6. Oxidation of
Succinate to E1-TPP is the most commonly defective enzyme component of the
Fumarate PDH complex.
7. Hydration of
Fumarate Congenital Lactic Acidosis:
8. Oxidation of Malate
to Oxaloacetate Ø Inability to convert pyruvate to Acetyl-CoA increasing the
LEGENDS levels of lactate and pyruvate in serum, due to
conversion of pyruvate to lactate, catalyzed by lactate
-books dehydrogenase
-mentioned by the lecturer but was not in the ppt/lecture notes Ø Also the result of pyruvate carboxylase deficiency
- from old transes (catalyzes pyruvate à oxaloacetate)
-take note for exam
I. OBJECTIVES A. Pyruvate Dehydrogenase (E1)
STEP 1:
At the end of the lecture, the student should be able to:
1. Explain the key role of pyruvate in central metabolism
2. Illustrate the general nature of the pyruvate
dehydrogenate reaction and its coeffectors
3. Discuss the key control mechanism which regulates the
pyruvate dehydrogenase complex
4. Discuss the sources and fates of Acetyl-CoA in normal
metabolism
5. Explain the overall process which occurs in the
tricarboxylic acid cycle
6. Enumerate the key intermediates in the TCA cycle
7. Explain the concept of anapleurotic reactions
Figure 2. Step 1 of the PDH Complex (Dr. Reyes’ ppt)

Substrate: Pyruvate
Coenzyme: Thiamine Pyrophosphate (TPP)
Product: Hydroxyethylthiamine pyrophosphate (HETPP)

• Pyruvate dehydrogenase (wrongly termed as pyruvate

decarboxylase by scientists) decarboxylates pyruvate via its
interaction with Thiamine pyrophosphate (TPP), prosthetic group
of E1, releasing CO2 and forming Hydroxyethylthiamine
pyrophosphate (HETPP) as an intermediate
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 B. Dihydrolipoyl Transacetylase (E2) STEP 5:
STEP 2:
Substrate: E3-FADH2
Coenzyme: NAD+
Product: NADH + H+ and FAD

• The reduced flavoprotein (FADH2) is oxidized by NAD+, which in

turn transfers reducing equivalents to the respiratory chain
(ETC).
• The regeneration of the E3-FAD holoenzyme marks the
completion of the catalytic cycle
• NADH dissociates into the mitochondrial matrix where it serves
as a mobile carrier of reducing energy (enters the ETC)

Figure 3. Step 2 of the PDH Complex (Dr. Reyes’ ppt) A. INTRODUCTION

Substrate: HETPP
Coenzyme: Oxidized lipoamide
Product: Acetyl-Dihydrolipoamide and Ylid

• HETPP reacts with oxidized lipoamide, prosthetic group of E2, to

form dihydrolipoamide and acetyl TPP
• A release of one hydride group (H-) leads to the “swinging” of the
arms of the dihydrolipoamide, attaching the acetyl group to it
leading to the formation of acetyl-dihydrolipoamide and Ylid

The swinging arm of the reduced lipoamide effectively keeps the

acetyl group in the enzyme complex preventing it from leaving and
going to other side reactions Figure 6. Overview of Glycolysis and TCA cycle (Dr. Reyes’ ppt)

The enzyme complex never let go L • Also known as:

® Citric Acid Cycle
STEP 3: ® Krebs Cycle – in honor of Hans Krebs
• Pyruvate needs to be transferred to the mitochondria so it
could undergo further aerobic metabolism. Not all our cells strive
under anaerobic glycolysis.
• Site: Matrix of Mitochondrion
• Major Function: The final common pathway for oxidation of
carbohydrates, lipids and proteins via the formation of a
common metabolite, Acetyl CoA
Figure 4. Step 3 of the PDH Complex (Dr. Reyes’ ppt) • Acetyl CoA is converted into Citrate in the TCA cycle
Substrate: Acetyl-dihydrolipoamide Acetyl CoA
Coenzyme: CoA-SH
Product: Acetyl-CoA

• Dihydrolipoyl transacetylase catalyzes the transfer of the

acetyl group from acetyl-dihydrolipoamide to coenzyme A in the
presence of CoA-SH, forming Acetyl-CoA and dihydrolipoamide
• Highly exergonic and irreversible
• A reaction that results to the formation of compound with a high
energy thioester bond

B. Dihydrolipoyl Dehydrogenase (E3)

Figure 5. Step 4&5 of the PDH Complex (Dr. Reyes’ ppt)

STEP 4:

Substrate: Dihydrolipoamide
Coenzyme: FAD
Product: Oxidized lipoamide and FADH2

• The prosthetic group of dihydrolipoyl dehydrogenase, FAD, Figure 7. TCA cycle (Dr. Reyes’ ppt)
oxidizes the reduced lipoamide forming FADH2
• Reoxidation of E2 allows it to participate in multiple rounds of the
reaction

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• Acetyl CoA, formed from pyruvate by the action of pyruvate ® (1) Dehydration of citrate at carbon 3 to form cis-aconitate
dehydrogenase, is the major substrate for long-chain fatty acid then (2) rehydration of cis-aconitate at carbon 5 to form
synthesis in nonruminants (Harper’s ) isocitrate.
• Before you can enter the cycle itself: • Endergonic and Reversible
® Glucose à Pyruvate à Acetyl CoA
® Fatty Acids (from diet) à Acetyl CoA Inhibition:
® Ketone Bodies (hydroxybutyrates) à Acetyl CoA • Presence of fluorocitrate can exert an inhibitory effect on
® Dietary Proteins à Amino Acids à Acetyl CoA aconitase, causing citrate to accumulate.
® Acetate (Acetic acid/Vinegar) à Acetyl CoA • Citrate in great amounts contributes to a form of acidosis
• Substrates’/Intermediates’ Carbon (Cx)- Indicators of how
many carbons they have
• End Products: CO2, H2O, ATP The poison fluoroacetate is found in some of the plants, and
their consumption can be fatal to grazing animals. Some
B. REACTIONS OF THE TCA CYCLE fluorinated compounds used as anticancer agents and industrial
chemicals (including pesticides) are metabolized to fluoroacetate.
1. Synthesis of Citrate from Acetyl-CoA & Oxaloacetate It is toxic because fluoroacetyl-CoA condenses with
oxaloacetate to form fluorocitrate, which inhibits aconitase,
causing citrate to accumulate.

Aconitase is an example of a moonlighting enzyme which is

an enzyme that it is capable of performing multiple functions.
• closely resembles the iron receptor protein (IRP)
• could also help recognize anemia and actually help the
body cover for that anemia, so that it could recover
while waiting for the iron stores to be recovered by the
body.
• Although the aconitase reaction does not require
cofactors, it requires ferrous (Fe2+) iron in its catalytic
mechanism. This Fe2+ is involved in an iron–sulfur
center, which is an essential component in the
hydratase activity of aconitase (Trans, 2021A)
Figure 8. Citrate Synthesis (Dr. Reyes’ ppt)

Substrate: Acetyl-CoA & Oxaloacetate 3. Oxidation and Decarboxylation of Isocitrate

Enzyme: Citrate synthase
Product: Citrate (First tricarboxylic acid formed)
Reaction: Condensation

• Formation of a carbon-carbon bond between the methyl carbon

of Acetyl-CoA and the carbonyl carbon of oxaloacetate,
catalyzed by citrate synthase is considered as the rate-limiting
step (Pacemaker step) in the cycle
• Only reaction with C-C bond formation
• Exergonic and Irreversible, negative standard free energy

2. Isomerization of Citrate to Isocitrate

Figure 10. Oxidation & Decarboxylation of Isocitrate (Dr. Reyes’ ppt)

Substrate: Isocitrate
Enzyme: Isocitrate dehydrogenase
Product: a-keto-glutarate
Reaction: Oxidative decarboxylation, irreversible, exergonic

• A key or major regulatory enzyme

® Due to cases of fluorocitrate poisoning, the reaction
catalyzed by citrate synthase still remains to be the
pacemaker step.
• Requires divalent ions (Mg2+ /Mn2+) for decarboxylation step to
occur
Figure 9. Citrate Isomerization (Dr. Reyes’ ppt) • First oxidative decarboxylation in the cycle
• Produces the 1st of the 3 NADH released in the cycle
Substrate: Citrate • Isocitrate undergoes dehydrogenation catalyzed by isocitrate
Enzyme: Aconitase / Aconitase hydratase dehydrogenase to form an unstable keto-acid, oxalosuccinate
Product: Isocitrate • Oxalosuccinate is spontaneously decarboxylated at its β-
Reaction: Dehydration, Hydration carboxyl group, without the presence of an enzyme, forming
an α-ketoglutarate
• Isomerization of citrate to isocitrate by Aconitase /Aconitase
hydratase occurs in two steps:
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4. Oxidation and Decarboxylation of a-ketoglutarate 6. Oxidation of Succinate to Fumarate

Figure 13. Oxidation of Succinate to Fumarate

Figure 11. Oxidation & Decarboxylation of a-ketoglutarate
Enzyme: Succinate dehydrogenase aka Complex II
Substrate: a-ketoglutarate Substrate: Succinate
Enzyme: a-ketoglutarate dehydrogenase complex Product: Fumarate – trans conformation ONLY
• Multienzyme complex Reaction: Dehydrogenation, Reversible, Endergonic
® a-ketoglutarate dehydrogenase (E1)
§ Coenzyme: TPP Stereospecific
® Dihydrolipoamide succinyl transferase (E2) • Will only form trans conformation
§ Coenzyme: lipoic acid, Coenzyme A First Dehydrogenation Reaction
® Dihydrolipoamide dehydrogenase (E3) • Oxidizes substrate to form fumarate via succinate
§ Coenzyme: FAD, NAD+ dehydrogenase forming the 1st FADH2
Product: Succinyl CoA • Created double bond
Reaction: Oxidative decarboxylation, irreversible, exergonic Succinate dehydrogenase
• Complex II from ETC
• Multienzyme is very similar and has the same reaction • Only enzyme from Krebs Cycle found in Inner Mitochondrial
mechanism to PDH but this uses a different substrate (a- Membrane and participates in the electron transport chain
ketoglutarate) • Associated with FAD
• This is the second oxidative decarboxylation Inhibition
• Produces 2nd NADH and 2nd CO2 • Structure similar to succinate
Inhibition: Arsenite • Inhibits via competitive inhibition
• Inhibits a-ketoglutarate dehydrogenase ® Binds to active site
® Attacks the sulfhidryl groups § Cannot oxidize due to lack of -CH2-CH2 group
® Decreases activity of enzyme necessary for dehydrogenation
® Results to accumulation of a-ketoglutarate
7. Hydration of Fumarate
5. Cleavage of Succinyl CoA

Figure 14. Hydration of Fumarate

Enzyme: Fumarase/Fumarate dehydratase

Figure 12. Succinyl CoA cleavage Substrate: Fumarate
Product: L Malate
Substrate: Succinyl CoA Reaction: Hydration, Reversible, Endergonic
Enzyme: Succinyl CoA synthetase/Succinyl thiokinase
Product: Succinate • Addition of H2O across double bond of substrate yields L-Malate
Reaction: Substrate level phosphorylation (only SLP reaction in • Stereospecific for trans conformation of substrate (cis is not a
TCA cycle) substrate)

Substrate Level Phosphorylation Cis indicates that the functional groups are on the same side of
• Produces ATP even without the participation of molecular O2 the carbon chain, while trans indicates that they are on
• High energy thioester bond of succinyl CoA is cleaved by opposite sides
succinyl thiokinase to succinate
• Formation of GTP Remember:
• Nucleoside diphosphate kinase (NuDiKi): converts GTP to In the citric acid cycle, the overall standard free energy
ATP dictates its effectivity as an energy yielding process not the
® 2 ATPs from the 2 pyruvate that entered the TCA individual reactions. That is why step 6 and step 7 still proceed
• Uses Pi and Mg2+ as cofactors even if the standard free energy of their reactions is zero.

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8. Oxidation of Malate D. SUMMARY OF KREBS CYCLE

Figure 15. Oxidation of Malate

Enzyme: Malate dehydrogenase

Substrate: L-Malate
Product: Oxaloacetate
Reaction: Oxidation, endergonic, reversible

• Produces 3rd NADH of the cycle

® Done by oxidizing the alcohol group from malate into a keto
group to form the product via the donation of electrons to
NAD+
• Oxaloacetate is free to react with another molecule of acetyl
CoA
C. ENERGETICS OF THE TCA
• Overall energetics value: ΔG0 -13.1 kcal, making it irreversible
and efficient as a system
® A highly exergonic process that allows the consistent
regeneration of oxaloacetate and conversion to acetyl CoA
Figure 17. Summary of the Krebs Cycle (Dr. Reyes ppt)
• Pyruvate becoming Acetyl-CoA as the linking reaction
® With the participation of NADH production
• Computation for the yield of ATP (including the linking reaction)
® Total: 12.5 if including the linking reaction
® Single turn of the cycle (excluding the linking reaction): 10
ATP
® For 2 molecules of pyruvate = 2 turns of the cycle = 10(2) =
20 ATP
• Steps with dehydrogenases are the steps where reducing
equivalents are produced
® Reducing equivalents go to the ETC for oxidative
phosphorylation in the mitochondria
▪ Substrate-level phosphorylation: no oxidation
happening, without the participation of molecular oxygen
• Very efficient as a system and can continuously proceed as a
cycle
® Anything that stops the cycle can have very dire
consequences for all aerobic metabolism across all cells

Inhibitors of the Krebs Cycle

Table 2. Inhibitors of the Krebs Cycle

Interfering in
Enzyme inhibited Enzyme inhibitor conversion of:

Aconitase Fluorocitrate Citrate —>

Isocitrate
Figure 16. Free energy change in the TCA cycle (Dr. Reyes ppt)
α-ketoglutarate Arsenite α-ketoglutarate —>
Table 1. Summary of the energy produced in each step of TCA cycle dehydrogenase Succinyl-CoA
Product Energy produced (in kcal) complex

Acetyl-CoA -7.7 (irreversible) Succinate Malonate Succinate —>

dehydrogenase Fumarate
Citrate 1.5
E. FATES OF CARBON ATOMS IN THE KREBS CYCLE
Isocitrate -5.3 (irreversible)
• The fates of the carbon atoms as the cycle proceeds
α-ketoglutarate 8 ® Acetyl CoA: 2 carbon atoms
▪ 6 carbon atoms are maintained from citrate to isocitrate
Succinyl-CoA -0.7 (irreversible) - From reactions of aconitase to isocitrate
dehydrogenase
Succinate 0
® 4 carbons left at Succinate
Fumarate 0 ▪ Due to 2 decarboxylation processes at the following
reactions:
Malate 7.1 - Isocitrate dehydrogenase
- α-ketoglutarate dehydrogenase
Oxaloacetate TOTAL OF: ΔG0 = -13.1
▪ All 4 carbons until oxaloacetate
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 • α-ketoglutarate à can become glutamate / GABA (NT) or
F. CATABOLISM OF THE MAJOR NUTRIENTS CONVERGE ON glutamine
THE TCA CYCLE • Oxaloacetate à transaminated to aspartate à converted to
urea, purines, pyrimidines, and cytosine

Figure 19. Amphibolic Nature of TCA cycle

• Fatty Acid and Steroid Synthesis: occurs when isocitrate

Figure 18. Summary of Catabolic Reactions converged on TCA (Dr. Reyes ppt)
• Acetyl CoA is the common (end) product of protein,
carbohydrate and fat metabolism.
• Acetyl CoA enters the TCA cycle where GTP, NADH, FADH2,
and carbon dioxide are generated.
• NADH and FADH2 is then transported to the ETC, which is used
to drive the ATP synthase, to produce ATP (for cellular
respiration).
G. ROLE OF VITAMINS IN THE TCA CYCLE
dehydrogenase is inhibited by the accumulation of ATP and
NADH, leading to the export of citrate to the cytosol and
releasing Acetyl-CoA by citrate lyase
• Heme Biosynthesis: Succinyl CoA couples with glycine and if
acted upon by ALAS (ALA synthase) à aminolevulinic acid is
formed
• Cytochromes – hemoproteins
• Gluconeogenesis: oxaloacetate can be converted to malate,
which can enter gluconeogenesis in times of starvation
I. ANAPLEROTIC REACTIONS OF TCA

Table 3. Role of vitamins

Vitamin Active Form Function
Coenzyme for decarboxylation by
Thiamine
the pyruvate dehydrogenase
Pyrophosph
Thiamine complex, isocitrate
ate (TPP) /
(B1) dehydrogenase & α-ketoglutarate
Thiamine
dehydrogenase complex (Catalytic
Diphosphate
cofactors)
Flavin Cofactor for succinate
Riboflavin Adenine dehydrogenase (Catalytic
(B2) Dinucleotide cofactor)
(FAD)
Electron acceptor for isocitrate
Nicotinamide
dehydrogenase, α-ketoglutarate
Niacin Adenine
dehydrogenase complex & malate
(B3) Dinucleotide
dehydrogenase (Stoichiometric
(NAD+)
cofactor)
Cofactor attached to "active"
Pantothenic Component carboxylic acid residues, such as Figure 20. Anaplerotic Reactions of TCA Cycle
Acid of Acetyl CoA and Succinyl CoA
(B5) Coenzyme A (Stoichiometric cofactor) • Anaplerotic pathways permit replenishment of TCA cycle
•
intermediates or “filling up reactions”.
H. AMPHIBOLIC NATURE OF THE TCA CYCLE • “Filling up” of compounds are needed because they are also
•
utilized in other pathways. If the body does not have a system to
• Can participate in either anabolic or catabolic reactions refill it as fast as they are being used, there could be a stoppage
• Can act as a precursor for proteins, fatty acids and glucose
or problem in the TCA cycle.
synthesis
• Removal of any of the intermediates from the TCA cycle
• Oxaloacetate (C4) and Citrate (C6) are important
intermediates in the cycle removes the four carbons used to regenerate Oxaloacetate
• Amino Acid Synthesis: transamination reactions during each turn of the cycle → depletion of Oxaloacetate →
• Pyruvate à production of alanine and other amino acids impossible to continue oxidation of Acetyl CoA.

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• To keep the TCA cycle running, cells have to supply enough 4- • Malate dehydrogenase
carbon intermediates from degradation of carbohydrate or • Isocitrate dehydrogenase
certain amino acids to compensate for the rate of removal • a-ketoglutarate dehydrogenase
(Anaplerotic Reactions)
Table 4. Summary table for the regulation of the Kreb’s Cycle [2021A trans]
• First major anaplerotic reaction: formation of oxaloacetate by the
carboxylation of pyruvate, catalyzed by pyruvate carboxylase. Allosteric
Enzyme Allosteric Inhibitor
→ Important in maintaining sufficient concentration of Activator
oxaloacetate for the condensation reaction with acetyl-CoA ↑ ATP, NADH & acetyl CoA;
→ Rate limiting step of gluconeogenesis [#$%] [(#')] [#*+,-. /0#]
↑ , ,
→ Uses biotin as cofactor for transferring CO₂ to Oxaloacetate [#'%] [(#'] [/0#]
Pyruvate
▪ Uses ATP (endergonic) ratios Ca2+
dehydrogenase
→ Pyruvate can come from alanine, cysteine, glycine, (presence of sufficient energy
hydroxyproline, serine, threonine, tryptophan. supply of the cell as in a
• Important Anaplerotic Substrates: Glutamate and Glutamine resting state)
→ Yield α-ketoglutarate as a result of reactions catalyzed by ↑ ATP, NADH;
glutaminase and glutamate dehydrogenase ↑ Succinyl CoA
ADP
• Second major anaplerotic reaction in the body: reversible (“downstream” intermediate of
Citrate NAD+
conversion of glutamate to α-ketoglutarate the cycle);
synthase Ca2+
→ “If there is less of α-ketoglutarate, the body will look to ↑ Long chain fatty acyl CoA; Citrate
glutamate as a source for replenishing this portion of the Citrate
cycle” (product inhibitor)
→ Catalyzed by transamination (TA) and glutamate
dehydrogenase (GDH) Isocitrate ADP, NAD,
↑ ATP & NADH
→ Other amino acids include arginine, histidine, glutamine, and dehydrogenase Ca2+
proline.
α-ketoglutarate ↑ ATP, GTP, NADH
• Synthesis of succinyl CoA from propionyl CoA: Ca2+
dehydrogenase &succinylCoA
→ Propionyl CoA – can come from metabolism of odd chain
fatty acids Malate
→ Isoleucine, methionine, and valine also contributes to the ↑ ATP, NADH -
dehydrogenase
formation of propionyl CoA à succinyl CoA
• Amino acids – can be source of fumarate K. CLINICAL CORRELATION
• Aspartate, alanine & serine – sources of oxaloacetate • Beri Beri
• First vitamin deficiency disease studied by american
doctors here in the Philippines
Anaplerotic reaction – basis of ketogenic diet utilized in epileptic • ¨Not over washing rice is enough to prevent Beri Beri¨
patients • Types of Beri-beri
• A regular intake of small amounts of carbohydrates will • Wet type: Cardiac problems
be enough to trigger a idiosyncratic reactions • Dry type: Neurologic symptoms only
• If there is deficiency of acetyl-CoA à besides
carbohydrates, fatty acids and amino acids are also Biochemical Basis of Beri-Beri
sources of acetyl-CoA 1. Common among population with rice as the major food (Far
East)
J. REGULATION OF KREBS CYCLE 2. Aggravated by eating polished rice whose outer layer rich in
thiamine is removed
3. Thiamine pyrophosphate (the active form of thiamine) is a
coenzyme of pyruvate dehydrogenase and α-ketoglutarate
dehydrogenase
4. Deficiency of thiamine leading to:
• → ↓ TPP
• → impaired glucose oxidation esp. in the nervous system
• → ↓ ATP: muscle weakness and atrophy, pain in the limbs,
fatigue, cardiac enlargement
• → ↓ CO and edema due to ↓ venous return
5. Hence, neurologic and cardiovascular disorders due to dietary
deficiency of thiamine (Vit. B1)
Genetic Disorders of Carboxylic Acid Cycle
Table 5. Genetic Disorders of TCA cycle
Type Enzyme Defect
Paraganglioma
(or pheochomocytoma)
(tumors that can arise in any
Succinate dehydrogenase deficiency
system of the body that contains neural
Figure 21. Regulation of Krebs Cycle (Dr. Reyes ppt) crest cells)
• Regulation: Normal regulation wherein our body tells to slow Uterine and/ or Renal CA Fumarase deficiency
down but not totally stop the pathway Leigh Syndrome a-ketoglutarate dehydrogenase,
• Points exerting inhibitory controls: (mitochondrial disorder, entails succinate dehydrogenase,
• Pyruvate dehydrogenase shorter lifespan for people with this
fumarase deficiencies
syndrome)
• Citrate synthase
§ Primary pacemaker of the Kreb’s cycle Gliomas Isocitrate dehydrogenase deficiency

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 3. Starting with 1 acetyl CoA, how many ATPs are produced
L. ATP YIELD entering the CAC?
Table 6. ATP yield per molecule of acetyl CoA oxidized throughout the TCA Answer: 10 ATPs (abandon pyruvate linking rxn)
Reaction Mechanism ATP
Yield
Isocitrate dehydrogenase 2.5
1 NADH
a-ketoglutarate
Oxidation Phosphorylation 2.5
dehydrogenase
Substrate-level
Succinyl CoA synthase 1
Phosphorylation
Succinate 1 FADH2
1.5
dehydrogenase Oxidation Phospho.
1 NADH
Malate dehydrogenase 2.5
Oxidation Phosphorylation
• Total ATP Yield = 10 (for a single cycle)
• If combined with pyruvate (additional ATP yield):
• Pyruvate à Acetyl CoA à NADH, Oxid. Phospho à 2.5
• Total ATP Yield = 12.5 (1 pyruvateàPDH to TCA cycle)
4. Starting with glycogen producing glucose 6-phosphate, what
M. SHUTTLE MECHANISM FOR CYTOPLASMIC REDUCING is the end product of aerobic glycolysis?
EQUIVALENTS Answer: 2 pyruvate
COMPLETE OXIDATION OF 1 MOLE OF GLUCOSE 5. Starting with pyruvate, how many CO2 molecules are produced
• In glycolysis: upon complete metabolism in the CAC?
® 5-7 ATPs depending on the shuttle used Answer: Within the cycle = 2 CO2;
§ Malate-aspartate shuttle = 7 ATPs Include pyruvate à Acetyl CoA = 3 CO2
§ Glycerol-Phosphate shuttle = 5 ATPs
§ 1 NADH = 2.5 ATPs 6. Starting with a molecule of glucose, how many ATPs
§ 1 FADH2 = 1.5 ATPs are produced in its conversion to CO2 and H2O?
• In conversion of pyruvate to acetyl CoA before entering the Answer: 30-32 ATPs
TCA: 5 ATPs
• In TCA cycle: 20 ATPs V. REFERENCES
• Total ATP Yield = 30-32 ATPs • Dr. Reyes’ Lecture & Powerpoint
• 2021 A Trans
IV. REVIEW QUESTIONS • Harpers Illustrated Biochemistry 31st Edition

1. Starting with 1 pyruvate to make acetyl CoA, how many ATPs

are produced?
Answer: 2.5 ATPs

2. Starting with 1 pyruvate to make acetyl CoA and entering into the
CAC, how many ATPs are produced?
Answer: 12.5 ATPs

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