Regulation

Last updated on December 1, 2018 at 18:12

General rules:

  • If it’s a hormone, the regulation is always indirect
  • If it’s a hormone, the regulation is almost always covalent
  • If it’s a kinase or phosphatase, the regulation is almost always covalent
  • Something that’s not a protein can never regulate anything covalently

The (probably) most important are bolded.

Most of them are taken from Lehninger 6th edition. The “Page” column shows which page from the book has been used as a source.

Acetyl-CoA carboxylase

Substance Allosteric/covalent Direct/indirect Activated/inactivated Comments Page 
Glucose Transcriptional Indirect Through PP2A and ChREBP 609
Xylulose 5-phosphate Transcriptional Indirect Through PP2A and ChREBP 609
PP2A Transcriptional and covalent Indirect and direct Through ChREBP and directly 609, 679
Insulin Covalent Indirect Through PP2A 679
Citrate Allosteric Direct   842
Cholesterol Transcriptional Indirect Through LXR 871
Glucagon, epinephrine Covalent Indirect Through PKA 679
AMP Covalent Indirect Through AMPK 679
Palmitoyl-CoA Allosteric Direct   842

Carbamoyl phosphate synthetase I

Substance Allosteric/covalent Direct/indirect Activated/inactivated Comments Page
N-acetylglutamate Allosteric Direct   708
Acetyl-CoA Allosteric Indirect Through N-acetylglutamate 708
Glutamate Allosteric Indirect Through N-acetylglutamate 708
Arginine Allosteric Indirect Through N-acetylglutamate 709

Carnitine acyl-transferase 1 (CAT1, the enzyme that transports fatty acids to mitochondria for β-oxidation)

Substance Allosteric/covalent Direct/indirect Activated/inactivated Comments Page
Malonyl-CoA Allosteric Direct Malonyl-CoA is produced by ACC  

Fructose 1,6-bisphosphatase (FBPase-1)

Substance Allosteric/covalent Direct/indirect Activated/inactivated Comments Page
Glucagon Allosteric Indirect Through F26BP 606
AMP Allosteric Direct   605
Insulin Allosteric Indirect Through F26BP 606
F26BP Allosteric Direct   605

Glucokinase (hexokinase IV)

Substance Allosteric/covalent Direct/indirect Activated/inactivated Comments Page
Insulin Transcription Indirect   952
Glucose Transport out of the nucleus Indirect Through a regulatory protein 603
Low [ATP] Transcription Indirect   603
Fructose 6-phosphate Transport into the nucleus Indirect Through a regulatory protein 603

Glycogen phosphorylase

Substance Allosteric/covalent Direct/indirect Activated/inactivated Comments Page
Glucagon Covalent Indirect In liver, through PKA 621
Epinephrine Covalent Indirect In muscle and liver, through PKA 621
[Ca2+] ↑ Covalent Indirect In muscle. Ca2+ is the signal for muscle contraction 621
[AMP] ↑ Allosteric Direct In muscle 621
Insulin Covalent Indirect   621
PP1 Covalent Direct and indirect Indirect via phosphorylase kinase. They often ask about this! 621
Glucose Allosteric Direct   622

Glycogen synthase

Substance Allosteric/covalent Direct/indirect Activated/inactivated Comments Page
G6P Covalent and allosteric Indirect (covalent) and direct (allosteric) Covalent: By making it easier for PP1 to dephosphorylate 623 (covalent), ass. prof. Lengyel (allosteric)
PP1 Covalent Direct   623
Insulin Covalent Indirect by two ways Through PP1 and GSK3 623
Glucose Covalent Indirect By making it easier for PP1 to dephosphorylate 623
Casein kinase II Covalent Direct   623
Glucagon, epinephrine Covalent Indirect Through PKA 623
GSK3 Covalent Direct   623
AMPK Covalent Direct   Figure 23-40

Hexokinase I-III (not glucokinase)

Substance Allosteric/covalent Direct/indirect Activated/inactivated Comments Page
Insulin Transcription Indirect    
Glucose Allosteric Direct    548, 591
Glucose 6-phosphate Allosteric Direct   602, 762

HMG-CoA reductase

Substance Allosteric/covalent Direct/indirect Activated/inactivated Comments Page
Insulin Covalent Indirect Through PP2A 870
Low intracellular cholesterol Transcriptional Indirect Through SREBP and SCAP 871
Glucagon Covalent Indirect Through PKA 870
AMP Covalent Indirect Through AMPK 870
High intracellular cholesterol Proteolysis Indirect Through oxysterol with Insig 871

HMG-CoA synthase (mitochondrial, the one for ketone body synthesis)

Substance Allosteric/covalent Direct/indirect Activated/inactivated Comments Page
Acetyl-CoA Allosteric Direct   Biochem 1 lecture
Succinyl-CoA Covalent Direct By succinylation Biochem 1 lecture

PEP carboxykinase

Substance Allosteric/covalent Direct/indirect Activated/inactivated Comments Page
Glucocorticoids (liver) Transcriptional ? Only in liver  
Thiazolidinediones (in adipose tissue) Transcriptional ? Only in adipose tissue  
Glucocorticoids (adipose tissue) Transcriptional ? Only in adipose tissue  

Phosphofructokinase-1 (PFK1)

Substance Allosteric/covalent Direct/indirect Activated/inactivated Comments Page
F26BP Allosteric Direct   605
Insulin Allosteric and transcriptional Indirect Through F26BP  
AMP, ADP Allosteric Direct   762
ATP Allosteric Direct   762
Glucagon, epinephrine Allosteric Indirect Through F26BP  
Citrate Allosteric Direct   762

Pyruvate carboxylase

Substance Allosteric/covalent Direct/indirect Activated/inactivated Comments Page
Acetyl-CoA Allosteric Direct   608

Pyruvate dehydrogenase complex

Substance Allosteric/covalent Direct/indirect Activated/inactivated Comments Page
AMP Covalent Indirect Through pyruvate dehydrogenase kinase 654
CoA Allosteric Direct   654
NAD+ Allosteric Direct   654
Ca2+ Allosteric Direct   654
ATP Covalent Indirect Through pyruvate dehydrogenase kinase 654
Acetyl-CoA Allosteric Direct   654
NADH Allosteric Direct   654
Fatty acids Allosteric Direct   654

Pyruvate kinase

Substance Allosteric/covalent Direct/indirect Activated/inactivated Comments Page
F16BP Allosteric Direct   607
Insulin Covalent and transcriptional Indirect Covalent: Through PP1, only in liver

Transcriptional: Through ChREBP

607
ADP Allosteric Direct   762
ATP Allosteric Direct   762
Long-chain fatty acid Allosteric Direct   607
Acetyl-CoA Allosteric Direct   607
Alanine Allosteric Direct   607
Glucagon Covalent Indirect Through PKA, only in liver 607

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