Transcript CARBOHYDRATE METABOLISM - UNAIR | E

CARBOHYDRATE
METABOLISM
Kadek Rachmawati, M.Kes.,Drh
CARBOHYDRATE DIGESTION

AMYLUM digestion by amylase enzyme
Disaccharides digestion
► Glucose
is the most important carbohydrate
► Glucose is the major metabolic fuel of mammals,
except ruminants
► Monosaccharide from diet :
- Glucose
- Fructose
- Galactose
► Fructose and Galactose
glucose at the liver
Galactose Metabolism
Fructose Metabolism
 Blood glucose
carbohydrate metabolism
exist are :
1. Glycolisis
2. Glycogenesis
3. HMP Shunt
4. Oxidation of Pyruvate
5. Kreb’s Cycle
6. Change to lipids
 Fasting
blood glucose
carbohydrate
metabolism :
1. Glycogenolisis
2. Gluconeogenesis
GLYCOLISIS
 Glycolisis
oxidation of glucose
energy
 It can function either aerobically or anaerobically
pyruvate
 Occurs in the cytosol of all cell
 AEROBICALLY GLYCOLYSIS :
Pyruvate
Mitochondria
Asetil CoA
Kreb’s Cycle
lactate
oxidized to
CO2 + H2O + ATP
Glycolisis
 Most of the reaction of glycolysis are reversible,
except of three reaction :
1. Glucose
Glucose-6-phosphate,
catalyzed by Hexokinase / Glucokinase
 Hexokinase :
- Inhibited allosterically by its product
glucose-6-p
- Has a high affinity for its substrate
glucose
- available at all cell, except liver and islet cell
 Glucokinase :
- available at liver and islet cell
- in the liver
to remove glucose from the
blood after meal
2. Fructose-6-P
Fructose-1,6-biP
- catalyzed by Phosphofructokinase enzyme
- Irreversible
- Rate limiting enzyme in glycolysis
3. Phosphoenolpyruvate
Enol Pyruvate
- Catalyzed by Pyruvate kinase enzyme
 Oxidation of 1 mol glucose
8 mol ATP and 2
mol Pyruvate
 ANAEROBICALLY GLYCOLYSIS :
- The reoxidation of NADH through the
respiratory chain to oxygen is prevented
- Pyruvate is reduced by the NADH to lactate, by
Lactate dehidrogenase enzyme
Lactate dehydrogenase
 Pyruvate + NADH + H+
Lactate + NAD+
- Oxidation 1 mol glucose via anaerobically
glycolysis
2 mol ATP
 ANAEROBICALLY GLYCOLYSIS :
Respiratory chain is absence
Reoxidation of NADH
chain is inhibited
NAD+ via Respiratory
Reoxidation of NADH via lactate formation
allows glycolysis to proceed in the absence of
oxygen by regenerating sufficient NAD+
GLYCOLYSIS IN ERYTHROCYTE
• Erythrocyte lack mitochondria
•
•
•
respiratory
chain and Kreb’s cycle are absence
Always terminates in lactate
In mammals
the reaction catalyzed by
phosphoglycerate kinase may be bypassed by a
process that catalyzed Biphosphoglycerate mutase
Its does serve to provide 2,3-biphosphoglycerate
bind to hemoglobin
decreasing its affinity
for oxygen
oxygen readily available to
tissues
GLYCOLYSIS IN ERYTHROCYTE
OXIDATION OF PYRUVATE
• Occur in mitochondria
• Oxidation of 1 mol Pyruvate
CoA + 3 mol ATP
• CH3COCOOH + HSCoA + NAD+
(Pyruvate)
1 mol AsetylCH3CO-SCoA + NADH
(Asetyl-CoA)
• Catalyzed by Pyruvate dehydrogenase enzyme
• This enzyme need CoA as coenzyme
• In Thiamin deficiency, oxydation of pyruvate is
impaired
lactic and pyruvic acid
OXIDATION OF PYRUVATE
GLYCOGENESIS
• Synthesis of Glycogen from glucose
• Occurs mainly in muscle and liver cell
• The reaction :
• Glucose
Glucose-6-P
Hexokinase / Glucokinase
• Glucose-6-P
Glucose-1-P
Phosphoglucomutase
• Glucose-1-P + UTP
UDPG + Pyrophosphate
UDPG Pyrophosphorylase
GLYCOGENESIS
• Glycogen synthase catalyzes the formation of α•
1,4-glucosidic linkage in glycogen
Branching enzyme catalyzes the formation of α1,6-glucosidic linkage in glycogen
• Finally
the branches grow by further
additions of 1 → 4-gucosyl units and further
branching (like tree!)
SYNTHESIS OF GLYCOGEN
SYNTHESIS OF GLYCOGEN
GLYCOGENESIS AND GLYCOGENOLYSIS PATHWAY
Glycogenesis
Glycogenolysis
GLYCOGENOLYSIS
• The breakdown of glycogen
• Glycogen phosphorilase catalyzes cleavage of
•
•
•
the 1→4 linkages of glycogen to yield glucose-1phosphate
α(1→4)→α(1→4) glucan transferase transfer a
trisaccharides unit from one branch to the other
Debranching enzyme hydrolysis of the 1→6
linkages
The combined action of these enzyme leads to
the complete breakdown of glycogen.
GLYCOGENOLYSIS
Phosphoglucomutase
• Glucose-1-P
Glucose-6-P
Glucose-6-phosphatase
• Glucose-6-P
Glucose
• Glucose-6-phosphatase enzyme
•
•
a spesific
enzyme in liver and kidney, but not in muscle
Glycogenolysis in liver yielding glucose
export to blood
to increase the blood glucose concentration
In muscle
glucose-6-P
glycolysis
GLUCONEOGENESIS
Pathways that responsible for converting
noncarbohydrate precursors to glucose or glycogen
 In mammals
occurs in liver and kidney
 Major substrate :
1. Lactic acid
from muscle, erythrocyte
2. Glycerol
from TG hydrolysis
3.Glucogenic amino acid
4. Propionic acid
in ruminant




Gluconeogenesis meets the needs of the body for
glucose when carbohydrate is not available from the
diet or from glycogenolysis
A supply of glucose is necessary especially for nervous
system and erythrocytes.
The enzymes :
1. Pyruvate carboxylase
2. Phosphoenolpyruvate karboxikinase
3. Fructose 1,6-biphosphatase
4. Glucose-6-phosphatase
GLUCONEOGENESIS
GLUCONEOGENESIS FROM AMINO
ACID
GLUCONEOGENESIS FROM PROPIONIC ACID
CORY CYCLE
HMP SHUNT/HEXOSE MONO
PHOSPHATE SHUNT = PENTOSE
PHOSPHATE PATHWAY
• An alternative route for the metabolism
of glucose
• It does not generate ATP but has two
major function :
1. The formation of NADPH
synthesis
of fatty acid and steroids
2. The synthesis of ribose
nucleotide
and nucleic acid formation
HMP SHUNT
• Active in : liver, adipose tissue, adrenal
cortex, thyroid, erythrocytes, testis and
lactating mammary gland
• Its activity is low in muscle
• In erythrocytes :
• HMP Shunt provides NADPH for the
reduction of oxidized glutathione by
glutathione reductase
reduced glutathione removes H2O2
glutathione
peroxidase
HMP SHUNT
Glutathione reductase
• G-S-S-G
2-G-SH
(oxidized glutathione)
(reduced glutathione)
Glutathione peroxidase
• 2-G-SH + H2O2
G-S-S-G + 2H2O
• This reaction is important
accumulation
of H2O2 may decrease the life span of the
erythrocyte
damage to the membrane
cell
hemolysis
HMP SHUNT
BLOOD GLUCOSE
• Blood glucose is derived from the :
1. Diet
the digestible dietary carbohydrate yield glucose
blood
2. Gluconeogenesis
3. Glycogenolysis in liver
• Insulin play a central role in regulating
blood glucose
blood glucose
• Glucagon
blood glucose
• Growth hormone
inhibit insulin activity
• Epinefrine
stress
blood glucose
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