NIGERIAN DEFENCE ACADEMY

POST GRADUATE SCHOOL

DEPARTMENT OF BIOTECHNOLOGY
POST GRADUATE DIPLOMA IN BIOTECHNOLOGY

COURSE:
INTRODUCTORY BIOTECHNOLOGY
BTE 713

ASSIGNMENT

BY

CHRISTIANA IJEOMA CHUKWUEMEKA

NDAPGS/FS/BIT022022/P08488

FEBRUARY, 2023

THE KREB CYCLE

HISTORY OF THE KREBS CYCLE

The Krebs cycle is named after Hans Krebs, who discovered it. The citric acid cycle
and the tricarboxylic acid cycle are other names for it. It is a set of chemical
events required for cellular respiration that results in ATP (adenosine
triphosphate), a coenzyme energy carrier for cells. A waste product, carbon
dioxide, is also created, as are other sets of reactants necessary to restart the
initial reaction.

WHAT IS THE CITRIC ACID, TRICARBOXYLIC ACID (TCA), OR KREBS CYCLE?

The tricarboxylic acid (TCA) cycle, commonly known as the Krebs cycle or the citric
acid cycle, is the primary source of energy for cells and an essential component of
aerobic respiration. The cycle converts acetyl coenzyme A (acetyl CoA )'s chemical
energy into the reducing power of nicotinamide adenine dinucleotide (NADH).

The TCA cycle is part of the larger glucose metabolism whereby glucose is
oxidized to form pyruvate, which is then oxidized and enters the TCA cycle as
acetyl-CoA.
Half of the intermediates on which the cycle is based are also the starting point
for pathways leading to key molecules such fatty acids, amino acids, and
porphyrins. If any of these intermediates are thus misdirected, the cycle's
integrity is destroyed, and the cycle ceases to function. Only if the diverted
intermediate or a subsequent intermediate that leads to oxaloacetate can be
replaced by anaplerotic (refilling) processes can vital.

FULL KREBS CYCLE DIAGRAM

The TCA cycle is usually described beginning with acetyl-CoA (top position).
Follow the diagram clockwise in the direction of the arrows.
KREBS CYCLE INTERMEDIATES
These intermediates are numbered on the diagram below
Citrate
Isocitrate
Oxoglutarate
Succinyl-CoA
Succinate
Fumarate
Malate
Oxaloacetate (oxaloacetic acid)

GLYCOLYSIS, PYRUVATE OXIDATION AND THE KREBS CYCLE

The Krebs cycle is linked to glycolysis, which is the process of breaking a six-
carbon glucose molecule into two three-carbon pyruvate molecules. The cycle
reactions occur twice for each glucose molecule respired, as two pyruvic acid
molecules are produced. Glycolysis is an anaerobic reaction that happens in the
cell's cytoplasm. The remaining reactions in cellular respiration are aerobic,
needing oxygen, and take place in the cell's mitochondria. Pyruvate oxidation
converts three-carbon pyruvic acid molecules to a two-carbon molecule linked to
Coenzyme A known as acetyl CoA. Acetyl CoA is the product that enters the Krebs
cycle.
Chemical scheme of Krebs cycle - tricarboxylic acid (citric) cycle, 2d
illustration. Image Credit: Chromatos / Shutterstock
STEPS IN THE KREBS CYCLE
The Krebs cycle is a closed-loop set of reactions in eight steps:
The two-carbon acetyl CoA is mixed with a four-carbon oxaloacetic acid and
hydrolyzed to generate citric acid or citrate, a six-carbon molecule.
Citrate is then dehydrated and then hydrated to restructure its structure into
isocitrate, a six-carbon isomer of citrate.
Isocitrate is oxidized, and decarboxylation occurs, releasing a carbon dioxide
molecule. NAD+, a coenzyme, is reduced to generate NADH, another dinucleotide.
When the carbon molecule is removed, the five-carbon molecule α-ketoglutarate
is formed..
The α-ketoglutarate when a carbon molecule is oxidized, NAD+ is reduced to
generate NADH, and another carbon molecule is liberated. The resulting four-
carbon molecule interacts with Coenzyme A to form the unstable succinyl CoA
complex.
A phosphate group replaces Coenzyme A in succinyl CoA, which is then
transferred to ADP (adenosine diphosphate) to form ATP. Phosphate groups are
transferred from GDP (guanosine diphosphate) to GTP in some species (guanosine
triphosphate). The four-carbon molecule that remains is known as succinate. The
Krebs cycle's final steps regenerate oxaloacetic acid from succinate:
Succinate is oxidized to form the four-carbon molecule called fumerate. The
electron carrier FAD (flavin adenine dinucleotide), is reduced to FADH2 by the
transference of two hydrogen atoms.
The addition of a water molecule converts fumerate to malate, a four-carbon
compound.
The oxidation of malate regenerates the original reactant oxaloacetic acid. By
transferring one hydrogen atom, the coenzyme NAD (nicotinamide adenine
dinucleotide) is reduced to NADH.
PRODUCTS AND FUNCTIONS OF THE KREBS CYCLE
Two molecules of carbon, three molecules of NADH, one molecule of FADH2, and
one molecule of ATP or GTP are created in one cycle. Each glucose molecule
generates two acetyl CoA molecules, enough for two cycles. The per-glucose yield
can be calculated by multiplying these products by two. Though only one ATP (or
GTP) is directly created every cycle, the products NADH and FADH2 can make ATP
(or GTP) in a subsequent cellular respiration process known as oxidative
phosphorylation.
The Krebs cycle's primary role is to generate energy, which is then stored and
delivered as ATP or GTP. The cycle is also important in other biosynthetic
reactions where the intermediates produced are used to synthesize additional
compounds such as amino acids, nucleotide bases, and cholesterol. All cells that
utilise oxygen have the Krebs cycle. When combined with the process of oxidative
phosphorylation, the Krebs cycle generates the majority of the energy consumed
by aerobic cells, with humans receiving more than 95% of the energy produced.
WHERE DOES THE KREBS CYCLE TAKE PLACE?
The TCA cycle was first discovered in pigeon muscle tissue. It occurs in both
eukaryotic and prokaryotic cells. It is found in the matrix of the mitochondrion in
eukaryotes. It occurs in the cytoplasm of prokaryotes.
KREBS CYCLE PRODUCTS
Before the Krebs cycle begins, a glucose molecule must be converted to acetyl-
CoA. This process yields 2 acetyl-CoA molecules to be fed into the cycle. Thus, the
cycle proceeds twice per original glucose, yielding twice the products shown
below.
One TCA cycle "turn" yields 7 products:
GTP
3 NADH
FADH2, which is converted to UQH2 in the presence of coenzyme Q (ubiquinone)
2 CO2 (carbon dioxide)

WHAT IS PYRUVATE?
Pyruvate is a biological substance and a result of glucose metabolism that
combines with adenosine triphosphate and carbon dioxide at the start of the TCA
cycle, turning it into acetyl-CoA and adenosine diphosphate (ADP). It is frequently
included in the cycle's introduction or preparatory step.
Pyruvate is often derived from the glycolysis product pyruvic acid, which
dissociates fast in most natural systems, resulting in pyruvate.
Pyruvate is involved in a variety of biotransformations, as detailed in the page
Pyruvate Transformations.
THE TCA CYCLE IN RESEARCH
Metabolomics researchers are particularly interested in the TCA cycle.
Researchers can make inferences about diseases and evaluate the efficiency of
medicines by investigating the rates, by-products, enzyme activity, and other
characteristics of metabolic processes.
KEY TCA CYCLE ENZYMES
Malic dehydrogenase
α-Ketoglutarate dehydrogenase
Citrate synthase
Fumarase
Aconitase
TCA CYCLE APPLICATIONS
These TCA-related metabolic applications are commonly studied using stable
isotope-labeled compounds and mass spectrometry:
Lipid Metabolism
Amino Acid Metabolism
Protein Metabolism (Turnover)
Glucose Metabolism
Energy Expenditure
Metabolomics
TERMINOLOGY
Redox: The combined name of the complimentary oxidation and reduction
processes. Oxidation is the gaining of oxygen. Reduction is the loss of oxygen.
Hydration: The addition of a water molecule.
Dehydration: The subtraction of a water molecule.
Decarboxylation: The removal of a carboxyl group and the release of a carbon
dioxide molecule.
Isomer: Two compounds with the same formula but a different structural
arrangement of atoms.

REFRENCES
Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New York: W H
Freeman; 2002. Chapter 17, The Citric Acid
Cycle. https://www.ncbi.nlm.nih.gov/books/NBK21163/
Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New York: W H
Freeman; 2002. Section 17.1, The Citric Acid Cycle Oxidizes Two-Carbon
Units. https://www.ncbi.nlm.nih.gov/books/NBK22427/
RSCB Protein Data Bank- Molecule of the Month: Citric Acid
Cycle. http://pdb101.rcsb.org/motm/154
www.khanacademy.org/.../the-citric-acid-cycle
.Krebs H, Johnson W. 1980. The role of citric acid in intermediate metabolism
in animal tissues . [Internet]. Volume 117, Supplement : FEBS Letter. Available
from: https://core.ac.uk/download/pdf/82630174.pdf