PROTEIN CATABOLISM

PROTEIN CATABOLISM

▪ TRANSAMINATION
▪ OXIDATIVE DEAMINATION
▪ UREA CYCLE
TRANSAMINATION

▪ Transamination is the process by which amino groups are removed

from amino acids and transferred to acceptor keto-acids to generate
the amino acid version of the keto-acid and the keto-acid version of
the original amino acid.
TRANSAMINATION

▪ Amino acid transfer their amino groups to alpha-ketoglutarate.

▪ The carbon skeleton of the amino acid remains behind as an alpha-
ketoacid
Oxidative Deamination

▪ Occurs in the mitochondria

▪ The oxidation of the amino acid resulted to deamination, yield NH4
which will enter urea cycle pathway
▪ In oxidative deamination of glutamic acid, NAD+ is reduced to NADH,
generates alpha-ketoglutaric acid
▪ The NADH will enter ETC / oxidative phosphorylation and produce ATP
UREA CYCLE

▪ NH4 from oxidative deamination is converted to urea.

▪ NH4 is condensed with CO2 in the mitochondria to form an unstable
compound, carbamoyl phosphate.
▪ Carbamoyl phosphate is condensed with ornithine to produce
citrulline. Citrulline diffuses out of the mitochondria to cytoplasm
UREA CYCLE

▪ In the cytoplasm, citrulline is

condensed with aspartate,
forming argininosuccinate.
▪ Argininosuccinate is split into
arginine and fumarate
▪ Arginine is hydrolyzed to urea
and ornithine
UREA CYCLE
PORPHYRIN, HEME, HEMOGLOBIN
PORPHYRIN

▪ A group of organic compounds

of which many occur in nature.
▪ One of the best-known
porphyrins is heme, the
pigment in red blood cells.
▪ Heme is a cofactor of the
protein haemoglobin
HEMOGLOBIN

▪ an oxygen-transport protein.
▪ It is a tetramer composed of
two types of subunits
designated α and β, with
stoichiometry α2 β2.
▪ The heme molecules give
haemoglobin its red colour.
Heme

▪ an iron-containing compound
of the porphyrin class which
forms the nonprotein part of
hemoglobin and some other
biological molecules.
▪ transports oxygen from
the lungs to the tissues as well
as takes carbon dioxide from
the tissues to the lungs
Bilirubin

▪ an orange-yellow pigment that

occurs normally when part of
your red blood cells break
down
▪ initially breaks apart into
biliverdin, a green pigment
which is rapidly reduced to
bilirubin, an orange-yellow
pigment
ENZYME
ENZYME

▪ A large molecules that increase the rate of chemical reactions

without themselves undergoing any change
▪ Biochemical reactions in biological system take place usually at 37°C
and the reaction rate is fast.
▪ The enzymes are usually globular proteins.
▪ The RNA which also performs some biochemical reactions is called
ribozymes.
CLASSIFICATION AND NOMENCLATURE

▪ The first general principle of enzyme nomenclature is that the name

should end in -ase, for single catalytic entity (enzyme).
▪ The second general principle is that enzymes are principally classified
and named according to the reaction they catalyze.
▪ A third general principle adopted is that the enzymes are divided into
groups on the basis of the type of reaction catalyzed, and this,
together with the name(s) of the substrate(s) provides a basis for
naming individual enzymes.
CLASSIFICATION AND NOMENCLATURE (CON’T)
FACTORS AFFECTING ENZYME ACTIVITY

▪ The enzyme is present in the cellular environment with high

specificity and function.
▪ The rate of the enzyme activity is dependent on a number of factors
which include:
– the substrate concentration,
– the temperature at which the cell is growing
– the pH of the microenvironment where enzyme is present.
Substrate Concentration

▪ At low concentration of
substrate, there is a steep
increase in the rate of reaction
with increasing substrate
concentration.
▪ As the concentration of
substrate increases, the
enzyme becomes saturated
with substrate. As soon as the
catalytic site is empty, more
substrate is available to bind
and undergo reaction.
TEMPERATURE

▪ Much below ambient temperature, the rate of enzyme reaction is

very slow.
▪ An increase in temperature increases the enzyme activity since the
molecules now possess greater kinetic energy. The rate of enzyme
activity is maximum around 37 degree centigrade.
▪ Above 40 degree centigrade, the rate of reaction starts to decrease.
This is because of the beginning of denaturation of enzyme.
pH

▪ Extremely high or low pH values generally result in complete loss of

activity for most enzymes.
▪ pH is also a factor in the stability of enzymes.
▪ As with activity, for each enzyme there is also a region of pH optimal
stability.
ENZYME INHIBITORS

▪ are molecules that bind to enzymes and decrease their activity.

▪ The binding of an inhibitor can stop a substrate from entering the
enzyme's active site and/or hinder the enzyme from catalyzing its
reaction.
▪ Inhibitor binding is either reversible or irreversible
ENZYME INHIBITORS (CON’T)

Enzymes can be inhibited by any of the three mechanisms:

1. Competitively, when the substrate and inhibitor compete for

binding to the same active site, the binding is reversible.
2. Non-competitively, when the inhibitor binds somewhere else on
the enzyme molecule reducing its efficiency.
3. Un-competitively, bind only to the enzyme-substrate complex and
not to the free enzyme. Substrate-binding could cause a
conformational change to take place in the enzyme and reveal an
inhibitor binding site
Theories (Mechanism) of Enzyme
Catalysis (Action)

Fischer's Lock and Key Theory

Koshland's Induced Fit Theory

Fischer's Lock and Key Theory

▪ first postulated in 1894 by Emil Fischer. In this analogy, the lock is the
enzyme and the key is the substrate.
▪ Only the correctly sized key (substrate) fits into the key hole (active
site) of the lock (enzyme).

▪ Smaller keys, larger keys or incorrectly positioned teeth on keys

(incorrectly shaped or sized substrate molecules) do not fit into the
lock (enzyme). Only the correctly shaped key opens a particular lock.
Koshland's Induced Fit Theory

▪ The induced-fit theory assumes that the substrate plays a role in

determining the final shape of the enzyme and that the enzyme is
partially flexible.
▪ This explains why certain compounds can bind to the enzyme but do
not react because the enzyme has been distorted too much.
▪ Other molecules may be too small to induce the proper alignment
and therefore cannot react.
▪ Only the proper substrate is capable of inducing the proper
alignment of the active site.
Cofactors and Coenzymes
Cofactors and Coenzymes

▪ cofactor is the more general term for small molecules required for the
activity of their associated enzymes, which also includes metal ions.
▪ cofactors are split into two groups: coenzymes and prosthetic groups
(ions usually)
▪ Coenzymes are small organic molecules that link to enzymes and whose
presence is essential to the activity of those enzymes.
▪ Prosthetic groups are tightly bound to enzymes and participate in the
catalytic cycles of enzymes.
▪ Co-substrates are loosely bound coenzymes that are required in
stoichiometric amounts by enzymes.
Cofactors and Coenzymes
Prosthetics Group
▪ Flavin adenine dinucleotide
(FAD) is a prosthetic group that
participates in several
intracellular oxidation–
reduction reactions.
Co-substrate
▪ The molecule nicotinamide
adenine dinucleotide (NAD)
acts as a co-substrate in the
oxidation–reduction reaction
that is catalyzed by malate
dehydrogenase, one of the
enzymes of the citric acid cycle.
Various Vitamins Functions as Coenzyme
In summary

▪ Coenzymes, then, are a type of cofactor.

▪ They are small organic molecules that bind tightly (prosthetic
groups) or loosely (co-substrates) to enzymes as they participate in
catalyzis.