Extension of the human gluconeogenesis module that makes the choice of non-carbohydrate precursor explicit. The three physiological precursors enter the pathway at different points: lactate (via lactate dehydrogenase) and the glucogenic amino acid alanine (via alanine aminotransferase) are converted to pyruvate and so require the pyruvate carboxylase / phosphoenolpyruvate carboxykinase backbone, whereas glycerol enters lower down — glycerol kinase and cytosolic glycerol-3-phosphate dehydrogenase feed dihydroxyacetone phosphate directly into the triose-phosphate pool, bypassing pyruvate carboxylase and PEPCK entirely. All routes converge on the shared fructose-1,6-bisphosphatase step and the terminal endoplasmic-reticulum glucose-6-phosphatase system (G6PC1 plus the SLC37A4 antiporter). Because glycerol bypasses the carboxylation arm, pyruvate carboxylase is no longer required by every route: the only steps common to all precursor routes are the terminal G6PC1·SLC37A4 system, which is therefore the single universal gate of free-glucose output. The module is built to be evaluated against tissue expression so that, per tissue, one can ask not just whether gluconeogenesis is possible but which precursors a tissue is equipped to use.
All recommended fields populated.
✗ none found
No MODULE:gluconeogenesis_human_substrates deep-research report alongside the module YAML.
✓ every leaf node grounds to a representative protein.
✓ every declared conforms_to bundle matches its template motif.
11 gene-function check(s) reflected in core functions · 0 conflict(s) · 2 evidence or coverage gap(s) (13 comparison(s))
Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.
| Annoton | Participant | Function | Assessment |
|---|---|---|---|
| LDHA_activity | LDHA (L-lactate dehydrogenase A) UniProtKB:P00338 Gene |
L-lactate dehydrogenase (NAD+) activity GO:0004459 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| LDHB_activity | LDHB (L-lactate dehydrogenase B) UniProtKB:P07195 Gene |
L-lactate dehydrogenase (NAD+) activity GO:0004459 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| GPT_activity | GPT (alanine aminotransferase 1) UniProtKB:P24298 Gene |
L-alanine:2-oxoglutarate transaminase activity GO:0004021 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| GPT2_activity | GPT2 (alanine aminotransferase 2) UniProtKB:Q8TD30 Gene |
L-alanine:2-oxoglutarate transaminase activity GO:0004021 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| PC_activity | PC (pyruvate carboxylase) UniProtKB:P11498 Gene |
pyruvate carboxylase activity GO:0004736 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| PCK1_activity | PCK1 (cytosolic PEPCK) UniProtKB:P35558 Gene |
phosphoenolpyruvate carboxykinase (GTP) activity GO:0004613 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| PCK2_activity | PCK2 (mitochondrial PEPCK) UniProtKB:Q16822 Gene |
phosphoenolpyruvate carboxykinase (GTP) activity GO:0004613 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| GK_activity | GK (glycerol kinase) UniProtKB:P32189 Gene |
glycerol kinase activity GO:0004370 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| GPD1_activity | GPD1 (glycerol-3-phosphate dehydrogenase) UniProtKB:P21695 Gene |
glycerol-3-phosphate dehydrogenase (NAD+) activity GO:0141152 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| FBP1_activity | FBP1 (liver fructose-1,6-bisphosphatase) UniProtKB:P09467 Gene |
fructose 1,6-bisphosphate 1-phosphatase activity GO:0042132 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| FBP2_activity | FBP2 (muscle fructose-1,6-bisphosphatase) UniProtKB:O00757 Gene |
fructose 1,6-bisphosphate 1-phosphatase activity GO:0042132 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| G6PC1_activity | G6PC1 (glucose-6-phosphatase catalytic subunit 1) UniProtKB:P35575 Gene |
glucose-6-phosphatase activity GO:0004346 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| SLC37A4_activity | SLC37A4 (glucose-6-phosphate transporter) UniProtKB:O43826 Gene |
glucose-6-phosphate transmembrane transporter activity GO:0015152 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
9 complete review(s) · 3 with deep research · 2 missing review · 8 reviewed but lacking deep research
| Gene | Review | Complete | Deep research |
|---|---|---|---|
| FBP1 P09467 | ✓ | ✓ | ✓ |
| G6PC1 P35575 | ✓ | 39/40 | ✓ |
| GK P32189 | ✓ | 29/31 | ✗ |
| GPD1 P21695 | ✓ | ✓ | ✗ |
| GPT P24298 | ✓ | ✓ | ✗ |
| GPT2 Q8TD30 | ✓ | ✓ | ✗ |
| LDHA P00338 | ✓ | ✓ | ✗ |
| LDHB P07195 | ✓ | ✓ | ✗ |
| FBP2 (muscle fructose-1,6-bisphosphatase) O00757 | ✗ | — | — |
| PC P11498 | ✓ | ✓ | ✗ |
| PCK1 P35558 | ✓ | ✓ | ✗ |
| PCK2 (mitochondrial PEPCK) Q16822 | ✗ | — | — |
| SLC37A4 O43826 | ✓ | ✓ | ✓ |
Precursor-resolved extension of gluconeogenesis_human.yaml. All UniProt and GO ids verified. Glycerol entry bypasses PC/PEPCK, so the only steps shared by all precursor routes are the terminal G6PC1·SLC37A4 system (the universal gate). See modules/experimental/gluconeogenesis-context/resolve_substrates.py for the per-tissue "which precursors can this tissue use?" resolution against GTEx.
Requires the carboxylation backbone (PC then PEPCK).
Glycerol enters at dihydroxyacetone phosphate via glycerol kinase and cytosolic glycerol-3-phosphate dehydrogenase, downstream of the carboxylation arm, so it needs neither PC nor PEPCK.
The two-component ER system required by every precursor route, and hence the single universal gate of free-glucose output.