Glycolysis and Gluconeogenesis: Mnemonics

Glycolysis begins with the phosphorylation of glucose to glucose 6-phosphate (glucose-6-P) by hexokinase (HK). In subsequent steps of the pathway, 1 glucose-6-P molecule is oxidized to 2 Pyruvates with generation of:

  • 2 molecules of NADH (since, glycolysis is a cytosolic pathway, cytosolic NADH cannot cross inner mitochondrial membrane – its reducing equivalents are transfarred to the electron transport chain by either malate aspartate shuttle or glycerol 3-phosphate shuttle)
  • 2 molecules of ATP (substrate level phosphorylation – doesn’t require oxygen; only source of energy in anaerobic glycolysis)

Glycolysis is aerobic except in following conditions (in which anaerobic glycolysis occurs):

  1. Limited supply of oxygen: Renal medulla
  2. Few or no mitochondria: RBCs
  3. Greatly increased demands for ATP: Skeletal muscle during exercise

In anaerobic glycolysis, O2 is not needed to re-oxidize NADH (Lactate dehydrogenase or LDH reoxidizes NADH by reducing pyruvate to lactate)

glycolysis and gluconeogenesis

MNEMONIC: Glucose Gives Fructose which Fractures to GAP & DAP to Build 3 Ps & Pyruvate

In the mnemonic:

  1. 1st 3 stage: Begins with Glucose and Energy (ATP) is used
  2. 2nd 3 stage: 6 C molecule is Fractured (Split) into two 3 C GAP and DAP
  3. 3rd stage: Energy is Built and Pyruvate formed


  1. Kinase: adds or substracts phosphate (phosphorylates or dephosphorylates)
  2. Aldolase: breaks aldose (6 C) to two 3 C compounds (splitting)
  3. Isomerase: Changes one isomer of 3 C compound to another (isomerization)
  4. Mutase: Changes position of phosphate group (mutation)

1. Glucose

Glucokinase (liver/pancreas) & Hexokinase (ATP utilized to ADP) – Inhibited by G-6-P & Induced by Insulin

2. Glucose-6-Phosphate (G-6-P)

Isomerase (reversible reaction)

3. Fructose-6-Phosphate (F-6-P)

PhosphoFructoKinase/PFK (ATP utilized to ADP) – Rate limiting enzyme (Insulin stimulates, Glucagon inhibits)

4. Fructose-1,6-Biphosphate (F-1,6 P)


5. DihydroxyAcetone Phospate (DAP) and GlycerAldehyde-3-Phsopate (GAP) are isomers

  • Can isomerize from 1 form to another by Isomerase

    DAP forms Glycerol-3-Phosphate (G3P) by G3P Dehydrogenase; G3P goes into Triglyceride synthesis and Electron shuttle

GAP Dehydrogenase (H+ exchanges between 2 NAD and 2 NADH)

6. 1,3-Bisphosphoglycerate (1-3 BPG) – 2 molecules

  •  In RBCs: 2-3 BPG mutase form 2,3 DPG from 1,3 BPG which binds to β-chains of HbA and decreases affinity for oxygen – shifts oxygen dissociation curve to right

Phosphoglycerate kinase (2 ADP generates 2 ATP)

7. 3-Phosphoglycerate (3-PG) – 2 molecules


8. 2-Phosphoglycerate (2-PG) – 2 molecules


9. PhosphoEnolPyruvate (PEP) – 2 molecules

Pyruvate kinase/PK (2 ADP generates 2 ATP) – activated by F-1,6-P
  • PK deficiency: Hemolytic anemia, Increased 2,3-BPG, No Heinz bodies (RBCs are without mitochondria and are dependent upon anaerobic glycolysis – PK deficiency leads to decreased ATP leading to:

    loss of biconvex shape which gets destroyed in spleen

    decreased activity of Na+K+ATPase pump resulting in loss of ion balance and causes osmotic fragility

10. Pyruvate – 2 molecules

  • Aerobic: Enters mitochondria and forms Acetyl-CoA (under action of PDH) to undergo TCA cycle or Fatty acid synthesis
  • Anaerobic: Forms lactate (under action of LDH) by using NADH generated in glycolysis (G3P to 1,3 BPG)


  1. DAP is used in liver and adipose tissue for triglyceride synthesis
  2. 1,3-BPG and PEP are used to generate ATP by substrate level phosphorylation
  3. 3 Enzymes in pathway catalizes reactions that are irreversible – Gluco/Hexokinase, PFK-1, PK


In fasting, glycogen (for glycogenolysis) reserves decline dramatically in the 1st 12 hours, during which time gluconeogenesis increases (repreasents sole source of glucose after 24 hours). The substrates for gluconeogenesis are:

  1. Glycerol 3-Phosphate (G3P)
  2. Lactate (from anaerobic glycolysis) – forms pyruvate
  3. Gluconeogenic amino acids (from muscle – only leucine and lysine are ketogenic; all other amino acids are either mixed or purely glucogenic; major is alanine) – forms pyruvate

Since, the reaction catalyzed by Pyruvate Kinase (PK) is irreversible, pyruvate doesn’t undergo reversed cycle of glycolysis.

  1. Carboxylation: Pyruvate forms OxaloAcetate (OAA) – 3 C to 4 C
    • using mitochondrial enzyme Pyruvate Carboxylase (requiring biotin) which is activated by Acetyl-CoA (from beta-oxidation of fatty acids; Acetyl-CoA also inhibits PDH, thus shifting pyruvate to OAA from pyruvate carboxylase rather than TCA cycle)
  2. Malate Shuttle: OAA cannot leave mitochondria – hence, undergoes Malate shuttle; in cytoplasm, malate is oxidized back to OAA
  3. Return to reverse glycolysis: OAA forms PEP using PEP carboxykinase (GTP utilized to GDP)
    • PEP undergoes 3 reversible reactions to form Glyceraldehyde 3 Phosphate (GAP) then, undergoes 1 more reversible reaction to form Fructose 1,6 biphosphate (F 1,6 BP)
    • G3P forms DAP which undergoes reversible reaction to form F 1,6 BP
  4. Return to glucose using phosphatase:
    • The glycolytic reactions catalized by glucokinase and PFK-1 are irreversible, hence F 1,6 P goes a different pathway
    • Formation of Fructose 6-Phosphate (F6P) by Fructose 1,6 Biphsophatase
    • F6P isomerizes to G6P
    • G6P forms glucose by Glucose-6-Phosphatase (only in the liver; not found in skeletal muscle – muscle glycogen cannot serve as a source of blood glucose)


Glucagon will lower F 2,6 -BP and stimulate gluconeogenesis, wherease insulin will increase F 2,6-BP and inhibit gluconeogensis by action of PFK-2 enzyme.

  • Glucagon inhibit PFK 2 enzyme – decreased F 2,6 -BP – decreased biphosphatase inhibition (more gluconeogenesis)
  • Insulin stimulates PFK 2 enzyme – increased F 2,6 -BP – increased biphosphatase inhibition (more glycolysis)

Fructose 1,6 Biphosphatase is activated by ATP and Inhibited by AMP and F 2,6 -BP.

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