From the Guidelines
It is not possible to provide an exhaustive list of every rate-limiting enzyme in biochemistry, but key examples include thymidylate synthase (TS) in nucleotide synthesis, as well as hexokinase, glucokinase, phosphofructokinase-1, acetyl-CoA carboxylase, HMG-CoA reductase, carnitine acyltransferase I, pyruvate dehydrogenase, and phenylalanine hydroxylase in various metabolic pathways 1. These enzymes play critical roles in controlling the flow through metabolic pathways, often catalyzing the slowest, irreversible steps, and are subject to extensive regulation.
Importance of Rate-Limiting Enzymes
Rate-limiting enzymes are crucial in medicine and biochemistry because they are effective targets for drugs and are often dysregulated in metabolic diseases. For instance, thymidylate synthase is a target for fluorouracil (FU) in cancer treatment, where FU is converted to its active form, FdUMP, which inhibits TS, preventing DNA synthesis 1.
Examples of Rate-Limiting Enzymes
- Thymidylate Synthase (TS): Involved in the biosynthesis of thymidine, a nucleotide required for DNA synthesis and cell proliferation 1.
- Hexokinase and Glucokinase: Key enzymes in glycolysis, the process by which glucose is converted into pyruvate.
- Phosphofructokinase-1: Controls the pace of glycolysis by catalyzing the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate.
- Acetyl-CoA Carboxylase: Essential for fatty acid synthesis.
- HMG-CoA Reductase: Critical in cholesterol synthesis and the target of statin medications.
- Carnitine Acyltransferase I: Involved in fatty acid oxidation.
- Pyruvate Dehydrogenase: Links glycolysis to the citric acid cycle.
- Phenylalanine Hydroxylase: Important in amino acid metabolism.
Regulation and Clinical Significance
These enzymes are regulated through various mechanisms, including allosteric control, covalent modifications, and changes in enzyme concentration. Their dysregulation can lead to metabolic diseases, making them important targets for therapeutic interventions. For example, the regulation of iron metabolism involves several rate-limiting steps and enzymes, such as d-ALA synthase 2 (ALAS2) in heme synthesis, which is critical for erythropoiesis 1.
Conclusion is not allowed, so the answer just ends here.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Rate Limiting Enzymes in Biochemistry
The following are some of the rate limiting enzymes in biochemistry:
- Hexokinase (HK) - specifically HK-I and HK-II 2, 3, 4
- Phosphofructokinase-1 (PFK-1) 2, 5, 6
- Pyruvate kinase M2 (PKM2) 2, 5, 6
- 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) 2
- Fructose-1,6-bisphosphatase 5
Enzyme Specifics
- Hexokinase (HK) has different isoforms, including HK-I and HK-II, which have different subcellular distributions and metabolic roles 3, 4
- Phosphofructokinase-1 (PFK-1) is regulated by phosphorylation and by the level of fructose 2,6-bisphosphate 5
- Pyruvate kinase M2 (PKM2) is a key regulator of glycolysis and is also regulated by phosphorylation 2, 5
- 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) is an indirect rate-limiting enzyme that regulates the level of fructose 2,6-bisphosphate 2
Tissue Specific Enzyme Distribution
- Lymphocytes from different origins have different enzyme activities and isozyme patterns for hexokinase, phosphofructokinase, and pyruvate kinase 6
- Thymocytes have a larger amount of PFK M-subunits than peripheral blood T and non-T lymphocytes 6
- Peripheral blood T lymphocytes differ from non-T lymphocytes in the PK isozymes distribution 6