Glycolysis and Glucose Metabolism – 100 Vocabulary Flashcards

These 100 flashcards cover key terms, enzymes, transporters, intermediates, regulatory mechanisms, and clinical implications related to glycolysis and glucose metabolism as presented in the notes.

GLUT-1

Glucose transporter expressed in most tissues; mediates basal glucose uptake with low Km (~1 mM).

GLUT-2

Glucose transporter in liver, kidneys, and pancreas; high Km (~15–20 mM); removes excess glucose from blood.

GLUT-3

Glucose transporter present in most tissues; supports basal glucose uptake with low Km (~1 mM).

GLUT-4

Insulin-dependent transporter found in muscle and fat; translocates to the plasma membrane to remove glucose; Km ≈5 mM.

GLUT-5

Transporter in small intestine and testes responsible for fructose transport; not a major glucose transporter (Km ~10 mM).

Facilitated diffusion

Movement of glucose down its concentration gradient mediated by GLUTs; requires no energy.

SGLT

Sodium-dependent glucose cotransporter; secondary active transport moving glucose against its gradient.

SGLT2

Major renal transporter for glucose reabsorption in the kidney; inhibition reduces glucose reabsorption.

Gliflozins

SGLT2 inhibitors used clinically to lower blood glucose in type 2 diabetes.

Glycolysis

Pathway that oxidizes glucose to pyruvate with ATP and NADH production; hub of carbohydrate metabolism.

Cytosol

Cellular compartment where glycolysis occurs.

Glucose

Hexose sugar substrate that enters glycolysis, ultimately yielding energy and intermediates.

NADH

Reduced coenzyme generated in glycolysis; reoxidized in mitochondria or by LDH under anaerobic conditions.

NAD+

Oxidized form of nicotinamide adenine dinucleotide; accepts electrons during glycolysis.

Pyruvate

End product of glycolysis under aerobic conditions; can be converted to acetyl-CoA or lactate.

Lactate

End product of anaerobic glycolysis; formed from pyruvate via lactate dehydrogenase; used by liver for gluconeogenesis.

Aerobic glycolysis

Glycolysis with oxygen; NADH reoxidized by mitochondria; end product is pyruvate.

Anaerobic glycolysis

Glycolysis in hypoxic conditions; end product is lactate; NAD+ regenerated for glycolysis.

1,3-Bisphosphoglycerate

High-energy intermediate formed in glycolysis; substrate-level phosphorylation yields ATP via PGK.

3-Phosphoglycerate

Glycolytic intermediate downstream of PGK; used for serine biosynthesis.

Glyceraldehyde-3-phosphate (G3P)

Glycolytic intermediate oxidized by GAPDH to 1,3-BPG, generating NADH.

Dihydroxyacetone phosphate (DHAP)

Glycolytic intermediate isomerized to G3P; can feed lipid synthesis as glycerol-3-phosphate.

Phosphoenolpyruvate (PEP)

High-energy glycolytic intermediate; substrate for pyruvate kinase to form pyruvate.

Pyruvate kinase (PK)

Final glycolytic enzyme converting PEP to pyruvate; activity tightly regulated.

PK-L

Liver isozyme of pyruvate kinase; inhibited by phosphorylation (glucagon/epinephrine pathway).

PK-M

Muscle isozyme of pyruvate kinase; regulated by hormones (e.g., epinephrine) to meet energy needs.

PFK-1

Rate-limiting, committed glycolytic enzyme; activated by fructose-2,6-bisphosphate; inhibited by ATP and citrate.

PFK-2

Bifunctional enzyme (kinase/phosphatase) that controls fructose-2,6-bisphosphate; liver isozyme regulated by insulin/glucagon.

Fructose-2,6-bisphosphate

Potent activator of PFK-1; increases glycolysis by elevating PFK-1 activity.

Fructose-6-phosphate

Substrate for PFK-1; isomerized from glucose-6-phosphate.

Fructose-1,6-bisphosphate

Product of PFK-1 that is split into glyceraldehyde-3-phosphate and DHAP.

Glucose-6-phosphate (G6P)

Trapped intracellular form; product of hexokinase/glucokinase; entry point to glycolysis and PPP.

Hexokinase

Enzymes I–III; low Km, high affinity for glucose; inhibited by G6P; broad substrate specificity.

Glucokinase (hexokinase IV)

Liver and pancreatic beta-cell enzyme; high Km, high Vmax; not inhibited by G6P; glucose sensor in liver and beta cells.

Glucokinase regulatory protein (GKRP)

Regulates glucokinase by sequestration in the nucleus; modulates GK activity in response to glucose.

2,3-BPG

Bisphosphoglycerate that shifts HbO2 binding to enhance O2 delivery; RBC-restricted intermediate.

2,3-BPG mutase

RBC enzyme that converts 1,3-BPG to 2,3-BPG, enabling the RBC glycolytic shunt.

2,3-BPG phosphatase

Removes phosphate from 2,3-BPG to form 3-PG; regulates 2,3-BPG levels and O2 release.

Lactate dehydrogenase (LDH)

Catalyzes pyruvate ⇌ lactate; direction depends on NADH/NAD+ ratio and tissue needs.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)

Oxidizes G3P to 1,3-BPG, generating NADH in the process.

Enolase

Catalyzes conversion of 2-phosphoglycerate to phosphoenolpyruvate.

Phosphoglycerate kinase (PGK)

Catalyzes formation of ATP from 1,3-BPG via substrate-level phosphorylation.

Aldolase

Splits fructose-1,6-bisphosphate into glyceraldehyde-3-phosphate and DHAP.

Triose phosphate isomerase

Interconverts DHAP and G3P, linking DHAP to the main glycolytic pathway.

Glycerol-3-phosphate shuttle

DHAP-derived glycerol-3-phosphate feeds lipid synthesis and mitochondrial shuttle.

Arsenic poisoning - 1 arseno-3-phosphoglycerate

Arsenate substitutes for phosphate, blocks glyceraldehyde-3-phosphate dehydrogenase, altering glycolysis.

Arsenate inhibition of ATP synthase

Arsenate can interfere with F1 ATP synthase, forming ADP-arsenate that is rapidly hydrolyzed.

Warburg effect

Cancer cells show elevated glucose uptake and glycolysis even with oxygen; lactate production is common.

PET imaging

Diagnostic use of glucose analogs to localize highly glycolytic tissues (e.g., tumors).

Hexokinase I–III

Mammalian hexokinases with low Km and broad substrate specificity; inhibited by G6P.

MODY2

Maturity-onset diabetes of the young type 2 caused by glucokinase mutations; impaired insulin secretion.

Glucose sensor in beta cells

Glucokinase acts as a glucose sensor in pancreatic beta cells, influencing insulin release.

Glucokinase regulatory protein (GKRP) regulation

Regulates GK activity by sequestration, modulated by glucose and other metabolites.

Hypoxia

Low oxygen conditions; increases dependence on glycolysis for ATP production.

Oxygen debt

Additional O2 required after anaerobic metabolism to restore aerobic conditions and NAD+ balance.

RBC energy reliance on glycolysis

Red blood cells lack mitochondria, so glycolysis is the sole source of ATP.

2,3-BPG and oxygen delivery

2,3-BPG in RBCs decreases hemoglobin's affinity for O2, aiding O2 release to tissues.

NADH/NAD+ ratio influence on LDH direction

Relative amounts of NADH and NAD+ determine whether LDH favors pyruvate or lactate formation.

Methemoglobin reduction by NADH

NADH in RBCs helps keep hemoglobin in the reduced (functional) form.

Gluconeogenesis substrate lactate

Lactate from muscle can be converted to glucose in the liver (Cori cycle).

Gluconeogenesis versus glycolysis cross-talk

Glycolysis provides intermediates that feed gluconeogenesis and vice versa depending on energy needs.

Glycerol-3-phosphate and DHAP

DHAP can be diverted to glycerol-3-phosphate for TAG synthesis.

Serine biosynthesis from 3-phosphoglycerate

3-Phosphoglycerate serves as a precursor for serine synthesis.

Alanine formation from pyruvate

Transamination of pyruvate yields alanine, linking glycolysis to amino acid metabolism.

Oxaloacetate formation from pyruvate

Pyruvate can be carboxylated to oxaloacetate for gluconeogenesis or TCA anaplerosis.

Acetyl-CoA from pyruvate

PDH converts pyruvate to acetyl-CoA feeding the TCA cycle.

Adenosine monophosphate pathway regulation (cAMP/PKA)

Hormonal signals alter glycolysis via PKA and PFK-2/FBP-2 phosphorylation states.

Fructose 2,6-bisphosphate as the most potent PFK-1 activator

Fructose 2,6-bisphosphate strongly stimulates PFK-1, boosting glycolysis.

Covalent regulation of PK-L

Glucagon/epinephrine lead to PK-L phosphorylation and inactivation; insulin promotes dephosphorylation and activation.

Hormonal regulation—insulin vs glucagon

Insulin promotes glycolysis; glucagon/epinephrine inhibit glycolysis via signaling cascades.

MODY2 diabetes mechanism

Diabetes caused by glucokinase mutations that raise blood glucose and impair insulin release.

Glycolysis’ energy yield (anaerobic)

Net 2 ATP per glucose produced during anaerobic glycolysis.

Glycolysis’ energy yield (aerobic)

Net 8 ATP per glucose when NADH is oxidized via the respiratory chain.

Basic glycolysis energy investment phase

First five reactions consume ATP to prepare glucose for cleavage.

Basic glycolysis energy generation phase

Subsequent reactions generate ATP and NADH from glyceraldehyde-3-phosphate onward.

Glucose-6-phosphate trapping

G6P cannot leave the cell due to lack of transporter; traps glucose inside.

G6P as branch point

Versatile intermediate feeding glycolysis, glycogenesis, and the pentose phosphate pathway.

Glycogenolysis linkage to glycolysis

Glycogen breakdown feeds glucose-6-phosphate for glycolysis in liver/muscle.

Alternative fates of pyruvate under anaerobic vs aerobic conditions

Aerobic: pyruvate enters TCA; Anaerobic: pyruvate becomes lactate via LDH.

Energy investment vs generation phases in glycolysis

Two stages: investment (ATP consumed) and generation (ATP produced).

2,3-BPG mutase vs phosphatase balance

Mutase forms 2,3-BPG; phosphatase reverts it to 3-PG, regulating O2 delivery.

Glycolysis and RBC metabolism

RBCs rely on glycolysis for ATP and produce 2,3-BPG to modulate oxygen delivery.

Arsenic’s biochemical toxicity on glycolysis

Arsenate substitutes for phosphate, inhibits GAPDH, and disrupts ATP generation.

Arsenic’s broader toxicity (PDHC inhibition)

Arsenic compounds can inhibit enzymes (e.g., PDH) that require lipoic acid.

Lactic acidosis

Metabolic acidosis with elevated lactate and low pH, often due to hypoxia or shock.

Xenobiotics affecting glycolysis

Fluoride inhibits enolase, reducing lactate production by glycolysis.

Glycolysis’ biomedical significance

Key energy source in RBCs and skeletal muscle; linked to RBC disorders and cancer metabolism.

Role of glycolysis in cancer (Warburg)

Cancer cells favor glycolysis, often under hypoxic conditions, to meet energy and biosynthetic needs.

Glycolysis’ intermediates for biosynthesis

Intermediates feed serine synthesis, glycerolipid synthesis, amino acid production, etc.

Regulation by citrate

Citrate inhibits PFK-1, linking glycolysis to the TCA cycle’s status.

Glycolytic enzyme localization

Most glycolytic enzymes operate in the cytosol of all cells.

Liver glycolysis during hyperglycemia

Glucokinase activity and GKRP interactions help manage postprandial glucose.

β-cell glucose sensing and insulin release

Glucokinase acts as a glucose sensor, modulating insulin secretion.

Hypoglycemia and neuronal response

Hypoglycemia triggers adaptive responses including activation of glycolysis in liver and brain.

Glycolysis in hypoxic tissues (eye, kidney medulla)

Tissues with low oxygen may rely on anaerobic glycolysis for ATP.

Correlation between glycolysis and PPP

Glucose-6-phosphate can enter glycolysis or the pentose phosphate pathway.

LDH isoforms and tissue specificity

LDH isoforms vary by tissue, influencing lactate production and clearance.

Gluconeogenesis relationship with glycolysis

Gluconeogenesis uses glycolytic intermediates in reverse pathways to generate glucose.

Cori cycle concept

Lactate from muscle is transported to liver for gluconeogenesis and glucose reuse.

Glycolysis’ role in energy balance

Provides rapid ATP and supplies intermediates for biosynthesis in many tissues.