The enzyme classification. PRESENTED BY:. JISHNU (23LBMB04) Sem II Int. M.Sc/Ph.D. Biochemistry and molecular biology.
CLASSES OF ENZYME. 1. 2. 3. 4. 5. 6. O: OXIDOREDUCTASES.
CLASS IV: LYASES. Lyases are the enzymes catalyze the non-hydrolytic removal of groups from substrates (without using any ATP), often leaving double bonds. Hence the E.C. no. of lyases are 4.x.y.z The second digit in the classification indicates the bond broken by the particular enzyme..
Glutamate Decarboxylase: The Enzyme Behind GABA.
Glutamate decarboxylase (GAD) (E.C. 4.1.1.15) is a crucial enzyme that plays a vital role in the central nervous system, by catalyzing the conversion of the amino acid L-glutamate into the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) using PLP (pyridoxal phosphate) as a cofactor. GAD helps maintain the delicate balance between excitatory and inhibitory signals in the brain. This process is essential for a wide range of biological functions, from locomotion and learning to the regulation of the circadian cycle. It is an unique enzyme among the other that are involved in the neurotransmitter synthesis as both its substrate and product act as a neurotransmitter and exhibits opposite functions..
Diversity of GAD Among various Species. Bacterial GAD.
The Two Isoforms of GAD. 1. GAD65. GAD65 is one of the two isoforms of GAD found in mammals, encoded by the _gad_ gene on chromosome 10. It has a molecular weight of 65,400 Da and is at least 15 times more efficient at catalyzing the reaction than GAD67. Its N-terminal consists of more cysteine residues that are the site for palmitoylation, accounting for membrane affinity..
Structural Aspect of GAD. Structure. Enzyme exists as a homodimer. Each monomeric unit consists of three domains. • N- terminal domain • PLP binding domain • C- terminal domain The it also consists of calmodulin binding domain that helps in enzyme regulation by binding to Ca++..
Differential Roles of GAD Isoforms. Synaptic GABA.
The Importance of GAD in Pancreatic Function GABA Signaling in Beta Cells Pancreatic beta cells also produce GABA and exhibit high GAD activity. In these cells, GABA acts as a signaling molecule, regulating protein biosynthesis and serving as an alternative energy source. GAD65 as an Autoantigen Pancreatic GAD65 has been identified as a target antigen for autoantibodies found in the blood of patients with type 1 diabetes. These autoantibodies are responsible for the destruction of beta cells, making GAD65 a valuable marker for early diagnosis. Therapeutic Potential Understanding the role of GAD and the autoimmune process targeting it in type 1 diabetes can help develop new therapies, such as using GAD65 injections to induce immune tolerance and prevent the progression of the disease..
Regulation of GAD Activity. 2. Cofactor Binding. The binding of the cofactor pyridoxal phosphate (PLP) is a highly regulated process and plays a major role in the short-term regulation of GAD enzyme activity. GAD65 is more responsive to PLP compared to GAD67..
GAD and Neurological Disorders. Diabetes Mellitus Type 1.
Concluding Remarks. Enzyme Function. Catalyzes the conversion of L-glutamate to GABA and CO2, using pyridoxal phosphate as a cofactor.
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