Rate limiting step in cholesterol synthesis is
1. HMG CoA synthetase
2. HMG CoA lyase
3. HMG CoA reductase
4. Mevalonate synthetase
📝 Explanation:
The rate limiting step in cholesterol synthesis is HMG CoA reductase. Here's
a detailed explanation:
Cholesterol synthesis is a complex process that involves multiple enzymatic
steps. This process begins with the condensation of acetyl-CoA molecules to form
acetoacetyl-CoA, which is then converted into HMG CoA
(3-hydroxy-3-methylglutaryl-CoA) by the enzyme HMG CoA synthetase. HMG CoA is
further converted to mevalonate by the action of HMG CoA reductase. This
reaction is the rate limiting step of the cholesterol synthesis pathway. The
rate limiting step is the slowest step in a metabolic pathway and is responsible
for controlling the overall rate of the process.
HMG CoA reductase is a critical regulatory enzyme that is tightly controlled
because it is the first committed step in the synthesis of cholesterol from
acetate. This enzyme is responsible for reducing HMG CoA to mevalonate, which is
the precursor of all isoprenoids, including cholesterol, steroids, and other
important biological molecules. The rate limiting nature of this step is due to
the fact that HMG CoA reductase is subject to both allosteric regulation and
feedback inhibition.
Allosteric regulation involves the binding of regulatory molecules, such as ATP,
citrate, and NADH, which can either activate or inhibit the enzyme. For example,
when cellular ATP levels are high, the enzyme is inhibited, which reduces
cholesterol synthesis. Conversely, when ATP levels are low, the enzyme is
activated, leading to increased cholesterol production. Citrate, a molecule
derived from the citric acid cycle, inhibits HMG CoA reductase when it builds up
in the cytosol, indicating that the cell has enough energy and does not need to
synthesize additional cholesterol.
Feedback inhibition occurs when the end product of the pathway, cholesterol,
binds to the enzyme and reduces its activity. This is a form of negative
feedback regulation that helps to maintain homeostasis of cholesterol levels
within the cell. When cellular cholesterol levels are high, the enzyme is
inhibited, which slows down the synthesis of new cholesterol molecules.
Conversely, when cholesterol levels are low, the enzyme is less inhibited, and
the synthesis rate increases.
The other enzymes listed, HMG CoA synthetase and mevalonate synthetase, are
involved in the synthesis of HMG CoA and the subsequent transformation of
mevalonate, but they are not the rate limiting steps. HMG CoA lyase, on the
other hand, is part of an alternative pathway that breaks down HMG CoA into
acetyl-CoA and acetoacetate. This enzyme is not directly involved in the rate
limiting step of cholesterol synthesis.
MCQ