Professional Documents
Culture Documents
By
Prof. Dr SOUAD M. ABOAZMA
BIOCHEMISTRY DEP.
DIGESTION OF CARBOHYDRATE
•Salivary amylase partially digests starch and glycogen to
dextrin and few maltoses. It acts on cooked starch.
Insulin
receptor
(nG)
Intracellular signal
for insulin
4- Mutases
These are enzymes that transfer a group from carbon to another carbon in
the same molecule. They are reversible enzymes.
e.g. Mutase
Glucose 6-P Glucose 1-P
5- Epimerases •
They are enzymes that transfer a group from a side to the opposite
side of one carbon atom in the molecule. They are reversible enzymes
e.g.
Epimerase
UDP-glactose UDP-glucose
6- Phosphatases
These are hydrolytic enzymes that remove a phosphate group from a
phosphorylated compound by addition of H2O. They are irreversible
enzymes.
H2O
Glucose 6-P Glucose + Phosphate
GLYCOGEN METABOLISM
ATP ADP
DUP-glucose pyrophosphorylase
2- G-1-P UDP-glucose
UTP PPi
H2O
pyrophosphatase
2Pi
N.B.: G-6-P is converted to glucose-1-phosphate by
phosphoglucomutase, glucose-1, 6 diphosphate is an obligatory
intermediate in this reaction.
Epinephrine PHOSPHODIESTERASE
(liver, muscle) cAMP Inhibitor-1
Glucagon 5’AMP Inhibitor-1
phosphate
(liver)
+
GLYCOGEN +
PHOSPHORYLASE
SYNTHASE b KINASE b
GLYCOGEN PHOSPHORYLASE
SYNTHASE a KINASE a
Glycogen
PHOSPHORYLASE PHOSPHORYLASE
UDPGIc b
a
Glucose 1-
phosphate
PROTEIN
Glucose(liver) Glucose Lactate(muscle) PHOSPHATASE-1
-
Differences between muscle and liver glycogen
The pathways for oxidation of glucose are classified into two main
groups:
a- The major pathways for complete oxidation of glucose
into CO2, H2O and energy are:
1- Glycolysis → convert one molecule of glucose into 2 mol of
pyruvic acid + 2 NADH.H+.
2- Oxidative decarboxylation of pyruvic to acetyl CoA +
NADH.H++CO2
3- Complete oxidation of acetyl CoA in Kerb’s cycle into CO2, H2O
and energy .
b- The minor pathways for oxidation, which are not for energy
production.
1- Hexose monophosphate pathway (HMP).
2- Uronic acid pathway.
GLYCOLYSIS
EMBDEN-MEYERHOF PATHWAY
Def.: oxidation of glucose to give pyruvic acid in presence of
O2 and lactic acid in absence of mitochondria (RBCs) and in
absence of O2 .
H C – OH H – C – OH
Hexokinase, glucokinase
OH – C – H OH – C – H
H – C – OH Mg H – C – OH
H – C – OH ATP ADP H – C – OH
CH2OH CH2O-P
D-Glucose
G-6-P
Mechanism of oxidation of glyceraldehydes 3-phosphate. Enz:
glyceraldehydes 3-P dehydrogenase which is inhibited by the –SH poison
iodoacetate, thus able to inhibit glycolysis.
ENERGY PRODUCTION FROM GLYCOLYSIS:
A. glycolysis in presence of O2 (Aerobic glycolysis):
Reaction catalyzed by ATP production
Stage I
1. Hexokinase/Glucokinase reaction (for -1 ATP
phosphorylation)
2. Phosphofrutokinase-1 (for -1 ATP
phosphorylation)
Stage III
3. Glyceraldehyde-3-P dehydrogenase + 6 or +4 ATP
(oxidation of 2 NADH in electron
transport chain)
4. Phosphoglycerate kinase (substrate level +2 ATP
phosphorylation)
Stage IV
5. Pyruvate kinase (substrate level +2 ATP
phosphorlyation)
Net gain = 10 or 8 - 2
= 8 or 6ATP
B. Glycolysis in Absence of O2 (Anaerobic glycolysis):
Pyruvate +TTP + Lipoic acid + CoA +FAD+ NAD+ --→ CO2 + Acetyl-CoA + NADH + H+
Steps of oxidative decarboxylation of pyruvic acid:
•Pyruvate is decarboxylated to form a hydroxyethyl
derivative bound to the reactive carbon of thiamine
pyrophosphate, the coenzyme of pyruvate decarboxylase.
•The hydroxyethyl intermediate is oxidized by transfer to the
disulfide form of lipoic acid covalently bound to dithydrolipoyl
transactylase.
•The acetyl group, bound as a thioester to the side chain of
lipoic acid, is transferred to CoA.
•The sulfhydryl form of lipoic acid is oxidized by FAD-
dependent dihydrolipoyl dehydrogenase, leading to the
regeneration of oxidized lipoic acid.
•Reduced flavoprotein is reoxidized to FAD by dihydrolipoyl
dehydrogenase and NAD+.
REGULATION OF OXIDATIVE DECARBOXYLATION OF
PYRUVIC ACID :
1- Product inhibition :
The enzyme complex is inhibited by acetyl CoA, which
accumulates when it is produced faster than it can be oxidized by
citric acid cycle. The enzyme is also inhibited by elevated levels of
NADH+.H, which occure when the electron transport chain is
overloaded with substrate and oxygen is limited.
2- Covalent modification:
The pyruvate dahydrogenase complex exists in two forms: an active
nonphosphorylated form and an inactive phosphorylated form.Phosphorylated
and nonphosphorylated pyruvate dehydrogenase can be interconverted by
two separate enzymes, a kinase and a phosphatase. The kinase is activated
by increase in the ratio of acetylCoA/ CoA or NADH/ NAD+. An increase in the
ratio of ADP/ATP, which signals increased demand for energy production ,
inhibits the kinase and allows the phosphatase to produce more of the active
,nonphosphorylated enzyme.
CLINICAL ASPECTS OF PYRUVATE METABOLISM:
Def.:
It is the series of reactions in mitochondria, which
oxidized acetyl CoA to CO2, H2O & reduced H2 carriers
that oxidized through respiratory chains for ATP
synthesis.
Site:
Mitochondria of all tissue cells except RBCs, which
not contain mitochondria. The enzymes of the cycle
are present in mitochondrial matrix except succinate
dehydrogenase, which is tightly bound to inner
mitochondrial membrane.
Steps:
ENERGY PRODUCTION:
ENERGY PRODUCTION FROM OXIDATION OF ONE MOLECULE OF GLUCOSE:
REGULATION OF KREB’S CYCLE:
1- As the primary function of TCA cycle is to provide energy, respiratory
control via the E.T.C and oxidative phosphorylation exerts the main control.
2- In addition to this overall and coarse control, several enzymes of TCA
cycle are also important in the regulation.
Three key enzymes are:
(a)Citrate synthase.
(b)Mitochondrial isocitrate dehydrogenase.
(c)α-ketoglutarate dehydrogenase.