NAME: GUTIERREZ, Mikaela Rose Self-Assessment No.

2 (1st Shifting)

YEAR/SECTION/COURSE: 3C-Biochemistry BCM6218 Lecture AY 2020-2021

Instruction: Answer the following questions and submit a clear photo or a scanned copy on the
designated folder in your BCM6128 course site. You may print this assessment or rewrite the
questions on a sheet of paper

1. What is Feedback Regulation? How is this concept related in the inhibition of HMG CoA
reductase enzyme by dietary cholesterol?
• Feedback regulation is a control mechanism that regulates the rate where the process occurs
such as metabolic pathway controls the activity of one or more enzymes in the pathway.
HMG-CoA reductase is described as a highly conserved enzyme, it catalyzes a rate-limiting
step in sterol, isoprenoid biosynthesis, and mevalonic acid. Cholesterol in our body can
either be ingested or can be synthesized.
• Feedback regulation is related to HMG-CoA reductase because the synthesis of cholesterol
begins with the condensation of two acetyl-coenzyme A (acetyl-CoA) molecules forming
acetoacetyl-CoA catalyzed by thiolase enzyme or acetyl-CoA acetyltransferase (ACAT)
followed by the reaction of two acetoacetyl-CoA molecules catalyzed by HMG-CoA synthase
(HMG-CoAS). The rate-limiting step of cholesterol synthesis begins by allowing the formation
of 3 hydroxy-3-methylglutaryl CoA (HMG-CoA) which will be reduced to mevalonate by the
enzyme HMG-CoA reductase and two NADPH molecules, the mevalonate will be converted
to two isoprenoids by addition of three ATP molecules. These two isoprenoids are used to
synthesize cholesterol.

Figure 1. Biosynthesis of Cholesterol

• As stated in the biosynthesis of cholesterol, HMG-CoA reductase is an important enzyme
that produce and regulate essential compounds, it also catalyzes the conversion of HMG-
CoA to mevalonate leading to two isoprenoids.
2. What is Feedback Inhibition? How is this concept related in the inhibition of aspartate-
transcarbamylase by CTP in pyrimidine synthesis?

• Feedback inhibition mechanism allows cells to regulate how much of an enzyme's product
is produced by slowing down the enzyme's activity. It happens in the allosteric site wherein
a biochemical product of a pathway blocks an enzyme at the beginning of the pathway.

Figure 2. ATCase reaction

• Aspartate transcarbamoylase is an example of allosteric enzyme from the bacterium
Escherichia coli (E.coli). It catalyzes the condensation of aspartate and carbamoyl
phosphate (CP) to produce N-carbamoylaspartate (CAA) beginning with the biosynthesis of
pyrimidine nucleotides such as cytidine triphosphate (CTP). Cytidine triphosphate (CTP) is
an allosteric inhibitor that represents feedback inhibition wherein the end product of a
biosynthetic pathway inhibits the enzyme that catalyzes the reaction at the beginning of
the pathway. CTP and Adenosine triphosphate (ATP) which is considered as an allosteric
activator act together on ATCase to stimulate and regulate purine and pyrimidine
nucleotide biosynthesis.
REFERENCES:

• Gesto, D. S., Pereira, C. M., Cerqueira, N. M., & Sousa, S. F. (2020). An Atomic-Level
Perspective of HMG-CoA-Reductase: The Target Enzyme to Treat Hypercholesterolemia.
Molecules, 25(17), 3891. doi:10.3390/molecules25173891
• Berg, J. M., Tymockzo, J. L., & Stryer, L. (2002). Section 10.1Aspartate Transcarbamoylase
Is Allosterically Inhibited by the End Product of Its Pathway. In Biochemistry 5th Edition.
W H Freeman &. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK22460/
• Cooperman, B. (2013). Allosteric Regulation. Encyclopedia of Biological Chemistry, 71-74.
doi:10.1016/b978-0-12-378630-2.00001-3
• Feedback regulation Definition and Examples - Biology Online Dictionary. (2020).
Retrieved August 29, 2020, from https://www.biologyonline.com/dictionary/feedback-
regulation
• Feedback Inhibition. (2019). Retrieved August 29, 2020, from
https://biologydictionary.net/feedback-inhibition/