Table 2 Reactions of glucose metabolism that produce or consume water, NADH, FADH₂, or ATP/GTP

A. Glycolysis

Glc → 2 Pyr

Hexokinase

Glc + ATP → Glc-6P + ADP

 − 1

Phosphoglucose isomerase

Glc-6P ↔ Fru-6P

Phosphofructokinase

Fru-6P + ATP → Fru-1,6P₂ + ADP

 − 1

Aldolase

Fru-1,6P₂ ↔ Gal-3P + DHAP

Triosephosphate isomerase

Gal-3P ↔ DHAP

Glyceraldehyde 3-P dehydrogenase^a

Gal-3P + Pi^a + NAD⁺  ↔ 1,3-bisphosphoglycerate + NADH + H⁺

0^a

0 ^a

 + 2

Phosphoglycerate kinase^a

1,3-bisphosphoglycerate + ADP ↔ 3P-glycerate + ATP

 + 2

Phosphoglycerate mutase

3P-glycerate ↔ 2P-glycerate

Enolase

2P-glycerate ↔ PEP + H₂O

 + 1

 + 2

Pyruvate kinase^a

PEP + ADP → Pyr + ATP

 + 2

Malate-Aspartate shuttle^b

(2NADH + 2H⁺)cytosol → (2NADH + 2H⁺)mitochondria to enter electron transport chain

Net from 1 Glc → 2 Pyr^b

(1 Pyr + NADH + H⁺  → lactate + NAD⁺)^b

 + 1

(+ 1)

 + 2 ^a

(+ 2)

 + 2

(+ 2)

 + 2

(0) ^b

B. Citric acid (TCA) cycle

Pyr → 3 CO₂

Pyruvate dehydrogenase

Pyr + CoASH + NAD⁺  → Acetyl CoA + CO₂ + NADH + H⁺

 + 2

Citrate synthase

Acetyl CoA + OAA + H₂O ↔ citrate + CoASH

 − 1

 − 2

Aconitase

Citrate ↔ isocitrate

Isocitrate dehydrogenase

Isocitrate + NAD⁺  → αKG + CO₂ + NADH + H⁺

 + 2

αKG dehydrogenase

αKG + NAD⁺  + CoASH → Succinyl CoA + CO₂ + NADH + H⁺

 + 2

Succinyl CoA synthetase ^a

Succinyl CoA + Pi^a + GDP → Succinate + GTP + CoASH

0 ^a

0 ^a

 + 2 GTP

Succinate dehydrogenase

Succinate + FAD ↔ fumarate + FADH₂

 + 2FADH₂

Fumarase

Fumarate + H₂O ↔ L-malate

 − 1

 − 2

NAD-L-malate dehydrogenase

L-Malate + NAD⁺  ↔ OAA + NADH + H⁺

 + 2

Net from 1 Glc via glycolysis + TCA cycle

 − 1

 − 2^a

 + 4

10 NADH + 2 FADH₂

C. Electron transport Water produced from transfer of electrons from NADH and FADH₂ to O₂ via Complexes I to IV along with pumping H⁺ from the matrix to IMS (17)

NADH + H⁺  → 2 e⁻ + NAD⁺ (Complex I)

    ~ 10 H⁺_matrix → 10 H⁺_IMS per 2e⁻ through Complex I to IV

 10 NADH + 10 H⁺ per Glc

FADH₂ → 2e⁻ + FAD (Complex II)

    ~ 6 H⁺_matrix → 6 H⁺_IMS per 2e⁻ through Complex II to IV

 2 FADH₂ per Glc

2 e⁻ + ½ O₂ + 2 H⁺  → H₂O (Complex IV)

    ~ 2 H⁺_matrix → 2 H⁺_IMS per 2 e⁻ though Complex IV

Net: ~ 10 × 10 H⁺_matrix + ~ 6 × 2 H⁺_matrix → 112 H⁺_IMS

Net: 6 O₂ + 24 H⁺  → 12 H₂O

+ 12

D. ATP synthase Dissipation of the IMS-matrix H⁺ gradient formed during electron transport is used by proton-translocating ATP synthase (Complex V) to drive synthesis of ATP + H₂O (17). H⁺/Pi transport into the mitochondria consumes 1 H⁺ per Pi and, with proton leakage, reduces the stoichiometry of H⁺ consumed per ATP synthesized (17)

30 H⁺_IMS + 30 Pi_IMS → 30 H⁺_matrix + 30 Pi_matrix (symport)

nH⁺_IMS + ADP + Pi → ATP + H₂O + nH⁺_matrix (ATP synthase)

n ≈ P/O ratio [34]

 ~ 2.5 ATP/NADH × 10 NADH/Glc = 25 ATP + 25 H₂O

 + 25

 + 25

 ~ 1.5 ATP/FADH₂ × 2 FADH_2/Glc = 3 ATP + 3 H₂O

+ 3

+ 3

Net: 28 ATP + 28 H₂O

Total of ~ 112 H⁺ translocated minus 30 H⁺ for Pi transport into matrix for ATP and GTP synthesis minus nH⁺ for proton leaks = < ~ 82 H⁺ to generate 28 ATP by ATP synthase. 82/28 = ~ 2.9 H⁺ pumped /ATP by ignoring proton leak and consumption of H⁺ for other processes that together reduce the P/O ratios to ~ 2.5 and ~ 1.5. For details, see discussions in references [17, 34]

E. Summary: Net water from metabolism of 1 Glc

Glycolysis + TCA cycle + electron transport + oxidative phosphorylation via ATP synthase: 1 Glc + 32 ADP + 32 Pi + 6 O₂ → 6 CO₂ + 38 H₂O + 32 ATP

Glycolysis + TCA cycle + electron transport:

1 Glc (C₆H₁₂O₆) + 6 O₂ → 6 CO₂ + 10 H₂O

Calorimetry (mass balance):

1 Glc (C₆H₁₂O₆) + 6 O₂ → 6 CO₂ + 6 H₂O

 + 38

 + 32

F. Pentose phosphate pathway

Production of NADPH for management of oxidative stress and for reductive biosynthesis and ribose-5P for nucleotide biosynthesis

3 Glc-6P + 6 NADP⁺  + 3 H₂O → 6 NADPH + 6 H⁺  + 3 CO₂ + 2 Fru-6-P + 1 Glyceraldehyde-3P (Gal-3P)

Glc-6P dehydrogenase

Glc-6P + 2NADP⁺  + H₂O → 2 NADPH + 2 H⁺  + CO₂ + ribulose-5P (Ru-5P)

 + 1

 + 1

 NADPH

Ribulose-5P isomerase

Ru-5P ↔ ribose-5P (R-5P)

Ribulose-5P epimerase

Ru-5P ↔ Xyulose-5P (Xu-5P)

Transketolase

R-5P + Xu-5P ↔ sedoheptulose-7-P (S-7P) + Gal-3P

C₅ + C₅ ↔ C₇ + C₃ (Subscripts denote the number of carbons (C))

Transaldolase

S7P + Gal-3P ↔ Fru-6P + erythrose-4P (E-4P)

C₇ + C₃ ↔ C₆ + C₄

Transketolase

E-4P + Xu-5P ↔ Fru-6-P + GAP → glycolytic pathway

C₅ + C4 ↔ C₆ + C₃

Net: per 3 Glc via the PPP

 + 1

 + 3

 + 6

G. Glycogen

Glucose storage and mobilization mainly in astrocytes

Synthesis: Glc-6P ↔ Glc-1P

Glc-1P + (Glycogen)_{n residues} → (Glycogen)_n+1

Degradation: (Glycogen)_{n residues} + Pi → (Glycogen)_n-1 + Glc-1P

Glc-1P ↔ Glc-6P → glycolytic pathway

Phosphoglucomutase

Glc-6P ↔ Glc-1P

UDP-Glc pyrophosphorylase

Inorganic pyrophosphatase

UTP + Glc-1P ↔ UDP-Glc + PPi (pyrophosphate)

PPi + H₂O → 2 Pi

0

 + 1

0

 + 1

-1

Glycogen synthase

UDP-Glc + (Glycogen)_{n residues} → (Glycogen)_n+1 + UDP

Glycogen phosphorylase

(Glycogen)_n + Pi → (Glycogen)_n-1 + Glc-1P (1 glucosyl unit)

Phosphoglucomutase

Glc-1P ↔ Glc-6P

Net for synthesis of 1 glucosyl unit from Glc-6-P

Net for degradation of 1 glucosyl unit to Glc-6-P

 + 1

0

 + 1

0

-1

0

1 Glycogen glucosyl unit → glycolytic pathway → 2 Lactate

 + 1

 + 2

 + 3

0

1 Glycogen glucosyl unit → oxidative pathway → 3CO₂

 + 38

 + 33