Skip to main content

Table 1 Classification of contributions to the inconsistency vector ( bottleneck; BN, invisible path; IP, chain disruptor; CD, close to input layer; CIL, close to output layer; COL, SIaa; Additional file 2 , SIcarb; Additional file 3 , SIlip; Additional file 4 , SIvit; Additional file 5 )

From: A network perspective on metabolic inconsistency

Contributor

Category

Topological class

Biological interpretation

Reference

AATAi**

unspecific

BN; IP

2-Aminoadipate transaminase;one out of two 2-oxoadipate producing reactions; missing GPR assoc. in all precursors.

SIaa, B1

PROD2*

unspecific

CD; CIL

Proline dehydrogenase; participates in a cycle that converts nadh to fadh2 (Figure 6); not expressed (Figure S5b).

SIaa, D3

DPMVDx

unspecific

CD

Diphosphomevalonate decarboxylase; essential step in the cholesterol biosynthesis pathway; not expressed; wrong or missing GPR assoc. (Figure S5c).

SIlip, B5

GLYK

unspecific

CIL

Glycerol kinase; not expressed in control and LIG, indicating that glycerol (provided in the in silico medium) might not be available as a in vivo medium component; slightly elevated expression levels in LIG (see Figure S5i).

SIlip, E5

PHETHPTOX2

unspecific

CIL

Phenylalanine 4-monooxygenase; converts phenylalanine (provided in the in silico medium) into tyrosine (not provided in the in silico medium); the high unspecific contribution strength indicates that tyrosine might be available as an in vivo medium component.

SIaa, A5

34HPPOR***

unspecific

CD; CIL

4-Hydroxyphenylpyruvate dioxygenase; involed in tryosine to fumarate and acetoacetate conversion; not expressed (see Figure S5m).

SIaa, B5

FUMtm

unspecific

Fumarate transport (cytosol/mitochondria); expression just below threshold (see Figure S5o).

no map

GLUTCOADHm**

specific

CD

Glutaryl-CoA dehydrogenase; involved in the 2-oxoadipate pathway (see Figure S5); elevated expression levels in LIG (see Figure S6a).

SIaa, A2

PDHm

specific

BN

Pyruvate dehydrogenase; entry point to the TCA cycle; elevated expression levels in LIG (see Figure S6c).

SIcarb, C3

MMEm

specific

CD

Methylmalonyl-CoA epimerase; involved in isoleucine degradation; slightly elevated expression levels in LIG (see Figure S6d).

SIaa, D1–E1

MEVK1x

specific

CD

Mevalonate kinase; an essential step in cholesterol biosynthesis; decreased expression levels in LIG and HIG (see Figure S6e).

SIlip, B5

G6PDH(1,2)rer

specific

Glucose-6-phosphate dehydrogenase; slightly elevated expression levels in LIG (see Figure S6f).

SIcarb, C4–D4

DHCR71r

specific

CD; COL

7-Dehydrocholesterol reductase; involved in cholesterol biosynthesis; slightly elevated expression levels in LIG (see Figure S6g).

SIlip, A4

HEX1

specific

CD; CIL

Hexokinase; first step in glycolysis; slightly elevated expression levels in LIG (see Figure S6h).

SIcarb, C4–C5

SQLEr

specific

CD

Squalene epoxidase; decreased expression levels in LIG and HIG (see Figure S6i).

SIlip, A5

  1. *Proline cycle issue; see Figure6.
  2. **2-Oxoadipate issue; see Figure7.
  3. ***Tyrosine path to fumarate and acetoacetate issue; see Figure S4 and Text S1.