Acetyl-CoA carboxylase (ACC) is an essential enzyme involved in fatty acid synthesis and regulation of fatty acid metabolism in cells. It plays a key role in converting acetyl-CoA, which is a central molecule in cellular metabolism, into malonyl-CoA. Malonyl-CoA is the C2 donor in the de novo synthesis of fatty acids, and it plays an important role as an inhibitor of the carnitine palmitoyl shuttle system for fatty acid oxidation.
There are two different isoforms of acetyl CoA carboxylase:
ACC1 is mainly found in the cytoplasm of cells, particularly in tissues involved in fatty acid synthesis, such as the liver, adipose tissue, and mammary glands.
ACC2 is primarily located in the mitochondria of cells, especially in tissues with high energy demands such as the heart and skeletal muscle.
ACC1 and ACC2 are encoded by two separate genes localized at chromosome 17q12 and 12q23, respectively. However, the amino acid sequences of ACC1 and ACC2 are approximately 80% identical.
ACC1 is a multifunctional enzyme encoded by a single gene. ACC1 is composed of three distinct functional units: biotin carboxylase, biotin carboxyl carrier protein, transcarboxylase. In presence of ATP, biotin carboxylase transfers CO2 from bicarbonate to the biotin carboxyl carrier protein, forming the carboxybiotin derivative. The transcarboxylase catalyzes the transfer of the carboxylase group to acetyl CoA forming Malonyl CoA. ACC1 is generally expressed in all tissues, it is expressed in more lipogenic tissues such as liver, adipose, and lactating mammary gland.
In contrast, ACC2 is highly expressed in heart, muscle and to a lesser extent in the liver. ACC1 derived malonyl-CoA is utilized by FAS for the synthesis of fatty acids in the cytosol. In contrast, the ACC2-generated malonyl CoA functions as an inhibitor of the carnitine/palmityl transferase 1 activity and the transfer of the fatty acyl group through CPT shuttle to inside the mitochondria for beta-oxidation.
Multiple choice questions:
1. Which of the following is the primary role of acetyl-CoA carboxylase in cellular metabolism?
6. What is the primary role of ACC2-generated malonyl-CoA in mitochondrial metabolism?
a) Breakdown of fatty acids
b) Conversion of glucose to pyruvate
c) Formation of acetyl-CoA from ketone bodies
d) Synthesis of malonyl-CoA and fatty acids
2. Where is the ACC2 isoform of acetyl-CoA carboxylase primarily located within cells?
a) Cytoplasm
b) Endoplasmic reticulum
c) Mitochondria
d) Nucleus
3. What is the role of malonyl-CoA generated by ACC1 in cellular metabolism?
a) Activation of fatty acid oxidation
b) Enhancement of protein synthesis
c) Inhibition of fatty acid synthesis
d) Promotion of glucose breakdown
4. Which enzyme, when activated during times of low energy, inhibits acetyl-CoA carboxylase activity?
a) AMP-activated protein kinase (AMPK)
b) Glucagon
c) Glycogen synthase kinase
d) Insulin
5. In which tissues is ACC1 predominantly expressed?
a) Brain and nervous tissue
b) Heart and skeletal muscle
c) Liver and adipose tissue
d) Pancreas and kidney
a) Enhancement of protein degradation
b) Inhibition of fatty acid oxidation
c) Promotion of fatty acid synthesis
d) Stimulation of gluconeogenesis
7. In which cellular compartment does fatty acid synthesis occur?
a) Endoplasmic reticulum
b) Golgi apparatus
c) Mitochondria
d) Nucleus
Answers:
1. d) Synthesis of malonyl-CoA and fatty acids
2. c) Mitochondria
3. c) Inhibition of fatty acid synthesis
4. a) AMP-activated protein kinase (AMPK)
5. c) Liver and adipose tissue
6. b) Inhibition of fatty acid oxidation
7. a) Endoplasmic reticulum