Biochemistry | Assessment | Repoort

RUNNING HEAD: BIOCHEMISTRY
BIOCHEMISTRY
Name of Student
Name of University
Author note

1BIOCHEMISTRY
Pyruvate dehydrogenase complex is formed by the combination of three enzymes
which is responsible for the conversion of pyruvate to acetyl-CoA. This happens by a
process known as pyruvate de-carboxylation. The important catalytic coenzymes involved in
this process are lipoic acid, thiamine pyrophosphate and FAD. The Pyruvate changes to
acetyl CoA by three main steps of de-carboxylation, transfer and oxidation of acetyl group
into Co-enzyme A.
The Pyruvate leads to acetyl-CoA formation by a three step reaction. Firstly,
decarboxylation: Thiamine pyro phosphate is combined with the pyruvate and decarboxylated
in order to yield hydroxyethyl Thiamine pyro phosphate (Martínez-Reyes et al., 2016).
Thiamine Pyro Phosphate in pyruvate dehydrogenase component, is called as ‘prosthetic
group’ because the very carbon atoms linked between sulfur and nitrogen atoms within
thizaole ring has been reported to be more acidic carbon groups whose kinetic values ‘pKa’
values are very near to 10. This biological reaction is then catalyzed by pyruvate de-
hydrogenase that is an integral component of multi enzyme complex. Carbon which is at the
center of Thiamine pyro phosphate is afterwards ionized to release a carbanion being added
to pyruvate’s carbonyl group. By decarboxylation, Thiamine pyro phosphate’s positively
charged ring then steadies the molecular negative charge that is then transferred to this ring.
The protonation process finally yields the very hydroxyethyl thiamine pyro phosphate.
Pyruvate + THYAMINE PYROPHOSPHATE (conenzyme thiamine pyrophosphate) +
2 H+ --> Hydroxyehthyl-THYAMINE PYROPHOSPHATE+ CO2
To conceive the acetyl group, the Thiamine pyro phosphate is further oxidized in this
oxidation process of the TCA cycle. At the same time, the hydroxyl ethyl group is moved to
lipoamide which is lipoic corrosive inferred that connects to the side chain of the very lysine
buildup by an amide linkage. This makes the development of a thioester bond which is very

2BIOCHEMISTRY
high in energy and hard to break. In this response, the di sulfide attachment of lipoamide goes
about as an oxidant and is diminished to the disulfhydryl structure. This response is supported
or accelerated by the enzyme pyruvate dehydrogenase part of E1 that lead to the formation of
acetyl lipoamide.
Fumarase a metabolic compound that takes part in the tri carboxylic acid or TCA
cycle, which actually catalyzes the change from (S) malate into the form of fumarate and also
H2O (water). There are two substrate restricting locales: the reactant A site, and the non-
synergist B site that may assume a job in the exchange of substrate or item between the
dynamic site and the dissolvable. Fumarate has also been found to hinder the very
dioxygenases that again hydroxylates or splits up the HIF further which is a translation factor
and prompts its action by VHL. The HIF turns on to oncogenic or cancer pathways, FH plays
a major and clear role in silencing of tumor action or the oncogenesis process. The enzyme
fumarase play a very crucial role in the formation of Fumarate and any block or rather a
metabolic block to this critical step of TCA can lead to various complex genetic or
oncological changes in the human body. Deformities in the structure of FH is the reason for a
condition known as genetic leiomyomatosis and also leads to renal cell malignant growth
(also known as HLRCC) which is a profoundly metastatic type or kind of RCC (Ryder et al.,
2017). Imperfections in FH are the reason for fumarase lack (FD) otherwise called
fumaricaciduria (Miettinen et al., 2016). FD is described by dynamic encephalopathy,
hypotonia, developmental delay, cerebral palsy cases and lactic-pyruvic acidemia. The cells
that are extracted from a patient who has HLRCC show revealed changes in oxidative
phosphorylation phase, reliance on anaerobic glycolysis, quick glycolytic motion, and
overexpression of lactate dehydrogenase A (or LDHA) plus that of GLUT1.
Complex I is the principal chemical of the mitochondrial electron transport chain.
There are three vitality transducing chemicals in the electron transport chain – that is NADH

3BIOCHEMISTRY
ubiquinone oxidoreductase (complex I), Coenzyme Q attached to cytochrome c reductase
(complex III), and cytochrome c oxidase (complex IV). Complex I is the biggest and most
convoluted protein of the electron transport chain (Birsoy et al., 2015). An electron transport
chain (ETC) occurs through a series of complexes that move the electrons to an electron
acceptor to an electron donator by means of a redox reaction (both decrease and oxidation
happening all the while). in this process, there is transfer of H + ions over the biological
membrane (Titov et al., 2016). This makes an electrochemical gradient that again drives the
production of adenosine triphosphate (ATP) which stores in its molecule, greatly stable high
energy bonds. The electron transport chain contains compounds, enzymes, peptides and
others. The last acceptor of ethe electrons transferred by the electron transport chain in the
process of areobic process is oxygen itself and in many anerobic conditions, it can be
sulphage. In this chain, there are a total of four complexes - Complex 1, II, III, IV.
The reaction which is catalyzed by the complex I is:
NADH + H+ + CoQ + 4H+in→ NAD+ + CoQH2 + 4H+out

4BIOCHEMISTRY
References
Birsoy, K., Wang, T., Chen, W. W., Freinkman, E., Abu-Remaileh, M., & Sabatini, D. M.
(2015). An essential role of the mitochondrial electron transport chain in cell
proliferation is to enable aspartate synthesis. Cell, 162(3), 540-551.
Martínez-Reyes, I., Diebold, L. P., Kong, H., Schieber, M., Huang, H., Hensley, C. T., ... &
Dufour, E. (2016). TCA cycle and mitochondrial membrane potential are necessary
for diverse biological functions. Molecular cell, 61(2), 199-209.
Miettinen, M., Felisiak-Golabek, A., Wasag, B., Chmara, M., Wang, Z., Butzow, R., &
Lasota, J. (2016). FUMARASE DEFICIENT UTERINE LEIOMYOMAS–AN
IMMUNOHISTO-CHEMICAL, MOLECULAR GENETIC, AND
CLINICOPATHOLOGIC STUDY OF 86 CASES. The American journal of surgical
pathology, 40(12), 1661.
Ryder, B., Moore, F., Mitchell, A., Thompson, S., Christodoulou, J., & Balasubramaniam, S.
(2017). Fumarase deficiency: A safe and potentially disease modifying effect of high
fat/low carbohydrate diet. In JIMD Reports, Volume 40 (pp. 77-83). Springer, Berlin,
Heidelberg.
Titov, D. V., Cracan, V., Goodman, R. P., Peng, J., Grabarek, Z., & Mootha, V. K. (2016).
Complementation of mitochondrial electron transport chain by manipulation of the
NAD+/NADH ratio. Science, 352(6282), 231-235.