Skip to main content
Fig. 6 | Arthritis Research & Therapy

Fig. 6

From: Lactate oxidative phosphorylation by annulus fibrosus cells: evidence for lactate-dependent metabolic symbiosis in intervertebral discs

Fig. 6

Proposed model of disc lactate metabolic symbiosis. A simplified model of disc lactate-dependent metabolic symbiosis showing the major steps of glucose metabolism starting with (1) glucose uptake via the Glut1 transporter into hypoxic NP cells, (2) conversion of glucose to pyruvate by glycolysis, (3) conversion of pyruvate to lactate by LDH5, (4) export of lactate out of NP cells through MCT4, (5) import of extracellular lactate into the more oxygenated AF cells via the MCT1, (6) conversion of lactate into pyruvate by LDH1, (7) conversion of pyruvate into acetyl-coA by PDH, which is negatively regulated by PDK, and (8) shuttle of acetyl-coA into the TCA cycle to generate precursors for biosynthesis and/or for oxidative phosphorylation to generate ATP. Below NP cell is shown the glycolytic pathway while below AF cell is the TCA cycle. Pyruvate to lactate converting enzyme (LDH-5), lactate exporter (MCT-4), lactate importer (MCT-1), and lactate to pyruvate converting enzyme (LDH-1) are shown. *Denotes the amino acids (green) and TCA metabolites (black) containing 13C derived from the heavy isotope 13C-lactate label. Malate conversion to oxaloacetate is the most thermodynamically unfavorable step in the TCA cycle with the ΔG = + 6.7 kcal mol

Back to article page