Creatine-phosphocreatine system (human)

A navigational grouping for the biology that Reactome bundles as "Creatine metabolism" (R-HSA-71288), assembled here as an explicit biological *system* rather than as a single GO metabolic process. The grouping is deliberately not called "creatine metabolism": GO keys metabolism on the chemical entity, and this system spans more than one entity. It comprises (1) de novo synthesis of the creatine molecule (creatine biosynthetic process, GO:0006601; the AGAT/GATM -> GAMT pathway), (2) the creatine kinase energy-buffer that interconverts creatine and phosphocreatine (phosphocreatine metabolic process, GO:0006603; including phosphocreatine biosynthesis GO:0046314 and the thermogenic futile creatine cycle GO:0140651), (3) inter-organ and cellular distribution of creatine by the SLC6A8 transporter, and (4) non-enzymatic disposal of creatine and phosphocreatine to creatinine for excretion (creatinine metabolic process, GO:0046449). In strict GO terms (2) is phosphocreatine metabolism, not creatine metabolism, so the canonical GO umbrella creatine metabolic process (GO:0006600) covers only (1) and the creatinine-forming arm of (4). This node carries both GO:0006600 and GO:0006603 to make that cross-branch span explicit. The detailed, protein-grounded logic lives in the dedicated modules referenced by each part; this document holds no annotons of its own and exists only to relate them.

MODULE:creatine_phosphocreatine_systemDRAFTBiological Processmodules/creatine_phosphocreatine_system.yaml
creatine metabolic processGO:0006600 phosphocreatine metabolic processGO:0006603 creatinine metabolic processGO:0046449
Reactome:R-HSA-71288
Creatine metabolism
Reactome groups creatine biosynthesis and the creatine kinase reactions under a single "Creatine metabolism" event; this system node mirrors that scope while keeping the GO branches distinct.
GO:0006600
creatine metabolic process
GO umbrella for metabolism of the creatine molecule (biosynthesis plus the creatinine-forming catabolic arm); its only biosynthetic child is GO:0006601.
GO:0006603
phosphocreatine metabolic process
The creatine kinase energy-buffer limb is, in GO, phosphocreatine metabolism rather than creatine metabolism; included here to make the cross-branch span of the system explicit.
Reactome:R-HSA-200396
Creatine transport across the plasma membrane
Reactome reaction grounding the SLC6A8 transport part of the system (now grounded to the reviewed human gene SLC6A8).
Reactome:R-HSA-71287
phosphocreatine => creatinine + orthophosphate
Reactome reaction for the spontaneous, non-enzymatic creatinine-disposal (catabolic) exit of the system, recorded at the concept level (GO:0046449).
4Nodes
3Parts
0Variant Sets
0Variants
1Annotons
3Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:creatine_phosphocreatine_system deep-research report alongside the module YAML.

Leaf nodes lacking representative members

2 leaf node(s) with no concrete protein grounding:

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Gene-review completeness (1/1 grounded genes reviewed)

1 complete review(s) · 0 with deep research · 0 missing review · 1 reviewed but lacking deep research

Gene Review Complete Deep research
SLC6A8 P48029 ✓ ✓ ✗

Details

Creatine-phosphocreatine systemBiological Processcreatine_phosphocreatine_system
creatine metabolic processGO:0006600 phosphocreatine metabolic processGO:0006603 creatinine metabolic processGO:0046449

Thin grouping/navigation node. The protein-grounded content lives in MODULE:creatine_biosynthesis (GATM/GAMT) and MODULE:phosphocreatine_shuttle (CKMT1A/CKMT2/CKB/CKM); the transport step is grounded directly here to SLC6A8 (UniProtKB:P48029). Named "creatine-phosphocreatine system" rather than "creatine metabolism" because the creatine kinase limb is phosphocreatine metabolism (GO:0006603) in GO, so the system spans two GO metabolism branches plus transport and creatinine disposal. Disposal to creatinine is the spontaneous, non-enzymatic catabolic exit (creatine/phosphocreatine cyclize to creatinine; Reactome:R-HSA-71287): it has no gene product, so it is recorded as a top-level concept (GO:0046449) rather than as a grounded step node, to avoid a permanent unfillable leaf-grounding gap. The biosynthesis_part and shuttle_part nodes are pointers to fully-grounded sibling modules; they surface in leaf-grounding QC only because the schema has no machine module-reference link.

Connections

biosynthesis_part -> transport_part Provides Input For
Synthesized creatine is distributed to consuming tissues by SLC6A8.
transport_part -> shuttle_part Provides Input For
Imported creatine is the substrate of the creatine kinase energy buffer.
biosynthesis_part -> shuttle_part Provides Input For
Locally synthesized creatine also feeds the kinase system directly.
Part 1: synthesis of creatine
Creatine biosynthesis (see MODULE:creatine_biosynthesis)Metabolic Pathwaybiosynthesis_part

Two-step AGAT/GATM -> GAMT synthesis of creatine from L-arginine and glycine. Detailed, protein-grounded logic is in MODULE:creatine_biosynthesis; this part is a pointer only.

creatine biosynthetic processGO:0006601
Part 2: distribution of creatine
Creatine transport (SLC6A8)Transport Steptransport_part

Na+/Cl--dependent import of blood-borne creatine into target tissues by the SLC6A8 creatine transporter, distributing creatine from synthesizing organs (liver) to consuming tissues (muscle, brain). Grounded to the reviewed human gene SLC6A8 (genes/human/SLC6A8).

creatine transmembrane transportGO:0015881

Annotons

SLC6A8: Na+/Cl--dependent creatine transporter
slc6a8_activity
Participant: Gene: SLC6A8 (creatine transporter 1, CRT)
Gene:
SLC6A8 (creatine transporter 1, CRT)UniProtKB:P48029
Reactome:R-HSA-200396
Creatine transport across the plasma membrane (Reactome reaction)

Function

creatine:sodium symporter activityGO:0005309
Substrates: creatine Na+ Cl-

Locations

plasma membraneGO:0005886

SLC6-family secondary active transporter; couples creatine import to the Na+ and Cl- electrochemical gradients. Loss of function causes X-linked cerebral creatine deficiency (creatine transporter deficiency).

Part 3: energy buffering via phosphocreatine
Phosphocreatine shuttle / creatine kinase system (see MODULE:phosphocreatine_shuttle)Metabolic Pathwayshuttle_part

Reversible creatine kinase interconversion of creatine and phosphocreatine across mitochondrial and cytosolic compartments, used to buffer and shuttle ATP. Detailed, protein-grounded logic is in MODULE:phosphocreatine_shuttle; this part is a pointer only.

phosphocreatine biosynthetic processGO:0046314 futile creatine cycleGO:0140651