What is HMG-CoA lyase deficiency?

What is HMG-CoA lyase deficiency?

3-hydroxy-3-methylglutaryl-CoA lyase deficiency (also known as HMG-CoA lyase deficiency) is an uncommon inherited disorder in which the body cannot process a particular protein building block (amino acid ) called leucine.

What regulates HMG-CoA synthase?

HMG-CoA synthase promoter activity is regulated by insulin or EGF. Luciferase activity in HaCaT keratinocytes transfected with a luciferase reporter construct containing the wild-type HMG-CoA synthase promoter.

Where is HMG-CoA synthesized?

The cytosolic or cholesterogenic isozyme provides the HMG-CoA destined for isoprenoid biogenesis, a process that occurs in the cytosol. Linkage analysis revealed that the mouse genes that encode the cytosolic and mitochondrial HMG-CoA synthases are located on different chromosomes.

Which of the following medications is an example of a drug from the HMG-CoA?

HMG-CoA reductase inhibitors (statins) Statins are used adjunctively with diet and exercise to treat hypercholesterolemia and are the most potent LDL-lowering medications. All statins have modest triglyceride-lowering and HDL-raising effects.

What is the meaning of HMG-CoA reductase inhibitors?

A substance that blocks an enzyme needed by the body to make cholesterol and lowers the amount of cholesterol in the blood. HMG-CoA reductase inhibitor drugs are called statins.

What regulates HMG-CoA reductase?

HMG CoA reductase has been long recognized as the rate-limiting enzyme in synthesis of cholesterol and as such is a primary focus of regulation. This is underscored by a multivalent system mediated by sterol and nonsterol isoprenoids that exerts stringent feedback control on reductase through multiple mechanisms 2.

What pathways is HMG CoA involved?

• β-Hydroxy β-methylglutaryl-CoA (HMG-CoA), also known as 3-hydroxy-3-methylglutaryl coenzyme A, is an intermediate in the mevalonate and ketogenesis pathways.
• HMG-CoA is a metabolic intermediate in the metabolism of the branched-chain amino acids, which include leucine, isoleucine, and valine.

How is HMG CoA reductase inhibited?

General information. Statins inhibit HMG-CoA reductase and reduce cellular cholesterol synthesis [1]. Lower intracellular cholesterol concentrations cause over-expression of the LDL receptor in the plasma membrane of hepatocytes.

What are the common adverse effects of HMG CoA reductase inhibitors?

The most common side effects of HMG-CoA reductase inhibitors include:

• Muscle aches, tenderness, or weakness (myalgia)
• Drowsiness.
• Dizziness.
• Headache.
• Nausea or vomiting.
• Bloating or gas.
• Diarrhea.
• Constipation.

In what circumstances would you discontinue therapy with HMG CoA reductase inhibitors?

In case of severe muscle symptoms or rhabdomyolysis, statins therapy should stop immediately, and patients require symptomatic care.

What happens if HMG CoA is inhibited?

Inhibition of HMG-CoA reductase, a rate-limiting enzyme in hepatic cholesterol synthesis by statins, results in the reduction of intracellular cholesterol content that in turn induces an increase in SREBP-2-mediated hepatic LDL receptor synthesis (Sahebkar and Watts, 2013b) (Chapter 11).

What is mitochondrial HMG-CoA synthase deficiency?

Mitochondrial HMG-CoA synthase deficiency is a rare inherited metabolic disorder that affects ketone-body synthesis. Acute episodes include vomiting, lethargy, hepatomegaly, hypoglycaemia, dicarboxylic aciduria, and in severe cases, coma.

What are the signs and symptoms of HMG-CoA lyase deficiency?

The signs and symptoms of HMG-CoA lyase deficiency usually appear within the first year of life. The condition causes episodes of vomiting, diarrhea, dehydration, extreme tiredness (lethargy), and weak muscle tone (hypotonia).

What is the difference between HMG-CoA and Reye syndrome?

HMG-CoA lyase deficiency is sometimes mistaken for Reye syndrome, a severe disorder that develops in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.