(2) Isozymes may differ from each other by differences in their amino acid sequences or by the presence of different posttranslational modifications in each isozyme.
Enzymes I
-Introduction to Enzymes
Lecture Outline
•What do enzymes do? •Why study enzymes? (Medical Relevance) •How do enzymes work?
What is the difference between an enzyme and a protein?
Catalytic RNA, or, ribozymes, satisfy several enzymatic criteria: substrate specificity, enhance reaction rate, and emerge from reaction unchanged;
Several known ribozymes:
• Five different isozymes of lactate dehydrogenase exist: H4, H3M, H2M2, HM3, and M4
Real Life - Tissue Specificity of Lactate Dehydrogenase
All of the lactate dehydrogenase isozymes catalyze the interconversion between lactate and pyruvate
Protein
Enzymes RNA
All enzymes are proteins except some RNAs and not all proteins are enzymes
Ribozymes
It was assumed that all enzymes are proteins until 1982 when Thomas Cech and Sydney Altman discovered catalytic RNAs (Nobel, 1989 in Chemistry);
Some definitions
• Apoenzyme = the protein part of an enzyme without coenzymes or prosthetic groups that are required for the enzyme to have activity. (Note: many enzymes do not have coenzymes or prosthetic groups bound to them).
• Coenzyme = small organic or inorganic molecules which are bound to the apoenzyme and are required for the enzyme to catalyze the chemical reaction.
• Prosthetic group = similar to a coenzyme, but is tightly bound to the apoenzyme. Heme is a prosthetic group in cytochrome c and hemoglobin.
O OC
NAD+
NADH + H+
O OC
HO CH
CO
CH3
L-lactate
NAD+
NADH + H+
Lactate dehydrogenase
(Muscle type)
CH3
pyruvate
O OC
NAD+
NADH + H+
O OC
HO CH
CO
CH3
L-lactate
NAD+
NADH + H+
Lactate dehydrogenase
Isozymes: An automotive analogy
Lactate Dehydrogenase is composed of fourቤተ መጻሕፍቲ ባይዱmonomers
H Heart type M Muscle type
HH MM HH MM HH HH HM HM MM MM
• Each monomer can be either heart or muscle type
(3) The relative abundance of different isozymes varies for different tissues. The ability to control which isozymes are expressed in a particular cell allows each cell to adjust the enzyme activity based on the specific conditions that exist in the cell.
• RNase P: catalyzes cleavage of precursor tRNA molecules into mature tRNAs;
• Group I, II introns: catalyze their own splicing (cleaving and ligating); • Ribosome: catalyzes peptidyl transfer reaction
• Holoenzyme = the apoenzyme with the coenzyme or prosthetic group bound to it .
• Isozyme
What is an isozyme?
(1) Isozymes are physically distinct forms of the same enzyme.