글리코젠 가인산분해효소

3. 구조

글리코젠 가인산분해효소 단량체는 크고, 근육 세포에서 842개의 아미노산으로 구성되어 있으며 97.434 kDa의 질량을 가진다. 이 효소는 비활성 단량체 또는 사합체로 존재할 수 있지만, 두 개의 동일한 서브 유닛으로 구성된 이량체로서 생물학적으로 활성화된다.^[4]

3. 1. 동위효소 (Isozymes)

4. 조절

글리코겐 가인산분해효소는 알로스테릭 조절과 인산화의 두 가지 방식으로 조절된다.

에피네프린(아드레날린), 인슐린, 글루카곤과 같은 호르몬은 G 단백질과 관련된 2차 전달자 증폭 시스템을 사용하여 글리코겐 가인산분해효소를 조절한다. 근육세포에서는 글리코겐 가인산분해효소 b가 AMP에 의해 알로스테릭하게 활성화될 수 있다.^[6][9]

4. 1. 알로스테릭 조절

4. 2. 공유 결합 변형 (인산화/탈인산화)

5. 임상적 의의

글리코젠 가인산분해효소 억제는 제2형 당뇨병 치료의 한 가지 방법으로 제안되었다.^[10] 간에서의 포도당 생산이 제2형 당뇨병 환자에게서 증가하는 것으로 나타났기 때문에,^[11] 간 글리코겐으로부터 포도당 방출을 억제하는 것이 유효한 접근 방식으로 보인다. 인간 간 글리코젠 가인산분해효소(HLGP)를 클로닝한 결과, 연구에 일반적으로 사용되는 토끼 근육 글리코젠 가인산분해효소(RMGP)에는 없는 소단위체 계면 근처의 새로운 알로스테릭 결합 부위가 발견되었다. 이 부위는 AMP 알로스테릭 부위의 억제제와 같은 억제제에는 민감하지 않았으며,^[12] 포도당-6-인산이 HLGP의 알려진 억제제이고 활성이 낮은 T-상태를 안정화시키기 때문에, 포도당 구조를 모방한 새로운 억제제를 합성하는 데 가장 큰 성공을 거두었다.^[13] 이러한 포도당 유도체들은 HLGP를 억제하는 데 어느 정도 성공을 거두었으며, 예측된 Ki 값은 0.016 mM 정도로 낮았다.^[14]

글리코젠 가인산분해효소의 뇌 아이소형(PYGB)은 위암의 생체 지표로 제안되었다.^[21]

5. 1. 맥아들병 (McArdle disease, 근육형 글리코젠 축적 질환, V형)

5. 2. 허스병 (Hers disease, 간형 글리코젠 축적 질환, VI형)

5. 3. 기타 질환

참조

_[1] PDB 3E3N
_[2] 간행물 Pyridoxal 5'-phosphate as a catalytic and conformational cofactor of muscle glycogen phosphorylase B 2002-10
_[3] 간행물 The role of pyridoxal 5'-phosphate in glycogen phosphorylase catalysis 1990-02
_[4] 간행물 Phosphorylase: a biological transducer 1992-02
_[5] 간행물 Quantitation of muscle glycogen phosphorylase mRNA and enzyme amounts in adult rat tissues 1986-01
_[6] 간행물 Glycogen phosphorylase: control by phosphorylation and allosteric effectors 1992-03
_[7] 간행물 The family of glycogen phosphorylases: structure and function
_[8] 간행물 Glycogen phosphorylase. The structural basis of the allosteric response and comparison with other allosteric proteins 1990-02
_[9] 간행물 Control of phosphorylase activity in a muscle glycogen particle. I. Isolation and characterization of the protein-glycogen complex 1970-12
_[10] 간행물 Glucose analog inhibitors of glycogen phosphorylases as potential antidiabetic agents: recent developments
_[11] 간행물 New drug targets for type 2 diabetes and the metabolic syndrome 2001-12
_[12] 간행물 An engineered liver glycogen phosphorylase with AMP allosteric activation 1991-08
_[13] 간행물 The design of potential antidiabetic drugs: experimental investigation of a number of beta-D-glucose analogue inhibitors of glycogen phosphorylase 1994-07
_[14] 간행물 Prediction of Ligand−Receptor Binding Free Energy by 4D-QSAR Analysis: Application to a Set of Glucose Analogue Inhibitors of Glycogen Phosphorylase 1999-09
_[15] 간행물 Molecular genetics of McArdle's disease 2007-01
_[16] 간행물 McArdle disease: molecular genetic update 2007-07
_[17] 간행물 Acute renal failure in McArdle's disease. Report of two cases 1972-06
_[18] 간행물 Mutations in the liver glycogen phosphorylase gene (PYGL) underlying glycogenosis type VI 1998-04
_[19] 간행물 Identification of a mutation in liver glycogen phosphorylase in glycogen storage disease type VI 1998-05
_[20] 간행물 A novel mutation (G233D) in the glycogen phosphorylase gene in a patient with hepatic glycogen storage disease and residual enzyme activity 2003-06
_[21] 간행물 Gastric and intestinal phenotypes of gastric carcinoma with reference to expression of brain (fetal)-type glycogen phosphorylase 2001-07
_[22] 간행물 The protein phosphatases involved in cellular regulation. Evidence that dephosphorylation of glycogen phosphorylase and glycogen synthase in the glycogen and microsomal fractions of rat liver are catalysed by the same enzyme: protein phosphatase-1 1986-04
_[23] 간행물 The Synthesis of a Polysaccharide From Glucose-1-Phosphate in Muscle Extract https://www.science.[...] 1939-05
_[24] 간행물 The kinetics of the enzymatic synthesis of glycogen from glucose-1-phosphate https://www.jbc.org/[...] 1940-07
_[25] 간행물 Crystalline Muscle Phosphorylase I. Preparation, Properties, and Molecular Weight https://www.jbc.org/[...] 1943-07-07
_[26] 간행물 Crystalline muscle phosphorylase II prosthetic group 1943-07
_[27] PDB 3E3N
_[28] 간행물 Pyridoxal 5′_Phosphate as a Catalytic and Conformational Cofactor of Muscle Glycogen Phosphorylase b
_[29] 간행물 The role of pyridoxal 5'-phosphate in glycogen phosphorylase catalysis
_[30] 간행물 Phosphorylase: a biological transducer
_[31] 간행물 Glycogen phosphorylase: control by phosphorylation and allosteric effectors
_[32] 간행물 The family of glycogen phosphorylases: structure and function
_[33] 간행물 Glycogen phosphorylase. The structural basis of the allosteric response and comparison with other allosteric proteins.
_[34] 간행물 Control of phosphorylase activity in a muscle glycogen particle. I. Isolation and characterization of the protein-glycogen complex
_[35] 간행물 Quantitation of muscle glycogen phosphorylase mRNA and enzyme amounts in adult rat tissues
_[36] 간행물 Glucose analog inhibitors of glycogen phosphorylases as potential antidiabetic agents: recent developments
_[37] 간행물 New drug targets for type 2 diabetes and the metabolic syndrome
_[38] 간행물 An engineered liver glycogen phosphorylase with AMP allosteric activation
_[39] 간행물 The design of potential antidiabetic drugs: experimental investigation of a number of beta-D-glucose analogue inhibitors of glycogen phosphorylase
_[40] 간행물 Prediction of Ligand−Receptor Binding Free Energy by 4D-QSAR Analysis: Application to a Set of Glucose Analogue Inhibitors of Glycogen Phosphorylase
_[41] 간행물 Molecular genetics of McArdle's disease
_[42] 간행물 McArdle disease: molecular genetic update
_[43] 간행물 Acute renal failure in McArdle's disease. Report of two cases
_[44] 간행물 Mutations in the liver glycogen phosphorylase gene (PYGL) underlying glycogenosis type VI
_[45] 간행물 Identification of a mutation in liver glycogen phosphorylase in glycogen storage disease type VI
_[46] 간행물 A novel mutation (G233D) in the glycogen phosphorylase gene in a patient with hepatic glycogen storage disease and residual enzyme activity
_[47] 간행물 Gastric and intestinal phenotypes of gastric carcinoma with reference to expression of brain (fetal)-type glycogen phosphorylase
_[48] 간행물 Crystalline muscle phosphorylase II prosthetic group http://www.jbc.org/c[...]
_[49] PDB 3E3N