View source for Enzymes and regulation

=== General rules about regulation: ===

* Hormones always regulate stuff indirectly
* Hormones almost always regulate stuff covalently
* Kinases or phosphatases almost always regulate stuff covalently
* Something that’s not a protein can never regulate anything covalently directly

The ones I think are most important are ''italicised''.

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 ===
Acetyl-CoA carboxylase (ACC) is the rate-limiting enzyme of fatty acid synthesis. It converts acetyl-CoA to malonyl-CoA with the help of the cofactors biotin, ATP and CO2. It is located in the cytosol.
{| class="wikitable"
|'''Substance'''
|'''Allosteric/covalent'''
|'''Direct/indirect'''
|'''Activated/inactivated'''
|'''Comments'''
|'''Page''' 
|-
|Glucose
|Transcriptional
|Indirect
|↑
|Through <abbr>PP2A</abbr> and <abbr>ChREBP</abbr>
|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 <abbr>PKA</abbr>''
|''679''
|-
|''AMP''
|''Covalent''
|''Indirect''
|''↓''
|''Through AMPK''
|''679''
|-
|''Palmitoyl-CoA''
|''Allosteric''
|''Direct''
|''↓''
| 
|''842''
|}

=== Carbamoyl phosphate synthetase I ===
Carbamoyl phosphate synthetase I (CPS I) is the rate-limiting enzyme of urea synthesis. It should not be confused with carbamoyl phosphate synthetase II, which is the rate-limiting step of de novo pyrimidine synthesis. It is located in the mitochondria.

N-acetylglutamate is a breakdown product of amino acids. When more amino acids are broken down the urea cycle is sped up (by the increased amount of N-acetylglutamate) to prevent ammonia, another breakdown product of amino acids, from accumulating.
{| class="wikitable"
|'''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 ===
Carnitine acyl-transferase 1 (CAT 1) is the main enzyme in the ''carnitine-dependent shuttle''. Fatty acids are activated in the cytosol (on the outer mitochondrial membrane), but they must be transported into the mitochondrial matrix to be oxidized. Short and medium-length fatty acids can freely diffuse across the mitochondrial membrane, but long fatty acids (like palmitoyl-CoA) cannot. Palmitoyl-CoA is instead converted into palmitoylcarnitine by CAT1, which is shuttled across the mitochondrial membrane by a transport protein. When inside the mitochondrial matrix, palmitoylcarnitine is converted back into palmitoyl-CoA.

It is the rate-limiting step of beta oxidation. Malonyl-CoA is a product of fatty acid synthesis. Because malonyl-CoA inhibits CAT1, fatty acid synthesis inhibits beta oxidation.
{| class="wikitable"
|'''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) ===
Fructose 1,6-bisphosphatase (FBPse-1) is the rate-limiting enzyme in gluconeogenesis. It is located in the cytosol.
{| class="wikitable"
|'''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) ===
Glucokinase is involved in glycolysis. It is located in the liver and beta-cells of the pancreas. Because glucokinase has a low affinity for glucose the liver will only store glucose as glycogen when the blood glucose level is high.
{| class="wikitable"
|'''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 ===
Glycogen phosphorylase is the rate-limiting step of glycogenolysis. It requires PLP as a cofactor.
{| class="wikitable"
|'''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''
|-
|<abbr>''PP1''</abbr>
|''Covalent''
|''Direct and indirect''
|''↓''
|''Indirect via phosphorylase kinase. They often ask about this!''
|''621''
|-
|''Glucose''
|''Allosteric''
|''Direct''
|''↓''
| 
|''622''
|}

=== Glycogen synthase ===
Glycogen synthase is the rate-limiting enzyme in glycogenesis (glycogen synthesis.
{| class="wikitable"
|'''Substance'''
|'''Allosteric/covalent'''
|'''Direct/indirect'''
|'''Activated/inactivated'''
|'''Comments'''
|'''Page'''
|-
|<abbr>''G6P''</abbr>
|''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 <abbr>GSK3</abbr>''
|''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) ===
Hexokinase is the rate-limiting step of glycolysis in all tissues except the liver and beta-cells. Because it has high affinity for glucose, all tissues that use hexokinase will utilize glucose even when the blood glucose level is normal.
{| class="wikitable"
|'''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 ===
HMG-CoA reductase (HMG-CoAR) is the rate-limiting enzyme of cholesterol synthesis. It is located in the membrane of ER.
{| class="wikitable"
|'''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) ===
Mitochondrial HMG-CoA synthase is the rate-limiting enzyme of ketone body synthesis. Cytosolic HMG-CoA synthase is an enzyme in the cholesterol synthesis, but it is not the rate-limiting one and is therefore not very important.
{| class="wikitable"
|'''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 ===
PEP carboxykinase is an irreversible enzyme in the gluconeogenesis. It is located in the cytosol.
{| class="wikitable"
|'''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) ===
Phosphofructokinase-1 (PFK1) is the rate-limiting enzyme in glycolysis.
{| class="wikitable"
|'''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 ===
Pyruvate carboxylase is an irreversible enzyme in the gluconeogenesis. It is located in the mitochondria and requires biotin and ATP.
{| class="wikitable"
|'''Substance'''
|'''Allosteric/covalent'''
|'''Direct/indirect'''
|'''Activated/inactivated'''
|'''Comments'''
|'''Page'''
|-
|''Acetyl-CoA''
|''Allosteric''
|''Direct''
|''↑''
| 
|''608''
|}

=== Pyruvate dehydrogenase complex ===
Pyruvate dehydrogenase complex (PDH) is an enzyme which connects the glycolysis to the TCA cycle by converting pyruvate to acetyl-CoA. It is located in the mitochondria. It requires 5 cofactors; TPP, lipoate, CoA, FAD and NAD.
{| class="wikitable"
|'''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 ===
Pyruvate kinase is an irreversible enzyme in the glycolysis.
{| class="wikitable"
|'''Substance'''
|'''Allosteric/covalent'''
|'''Direct/indirect'''
|'''Activated/inactivated'''
|'''Comments'''
|'''Page'''
|-
|''F16BP''
|''Allosteric''
|''Direct''
|''↑''
| 
|''607''
|-
|''Insulin''
|''Covalent and transcriptional''
|''Indirect''
|''↑''
|''Covalent: Through PP1, only in liverTranscriptional: 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''
|}
[[Category:Biochemistry help material]]