Carbohydrate

Metabolism
Sylvia Rianissa Putri
 Carbohydrate
• Definition: aldehyde or ketone derivatives of
polyhidric alcohols
• Classification:
– Monosaccharides
– Disaccharides
– Oligosaccharides
– Polysaccharides
 Carbohydrate
• Occurrence:
Tissues, tissue fluids,
– Humans. blood, milk, secretions,
excretions
– Animals.
– Plants.
– Microbes.
• Medical and Biological Importance:
– Major source of energy for man.
– Reserve food material in humans and in plants.
 Carbohydrate
• Medical and Biological Importance (cont.):
• Components of several animal and plant structures.
– Components of cell membrane and nervous
tissue.
– Components of nucleic acids and blood group
substances.
– Involved in cell-cell interaction.
 Carbohydrate
• Medical and Biological Importance (cont.):
– Some derivative of carbohydrates are drugs,
antibiotics, and water-soluble vitamin.
– Bacterial invasion involves hydrolysis of
mucopolysaccharides.
– Survival of antarctic fish in icy environment is due
to presence of anti-freeze glycoproteins in their
blood
Overview of Carbohydrate Metabolism
Catabolic:
• Glycogenolysis.
• Hexose monophosphate shunt.
• Oxidative decarboxylation (pyruvate oxidation).
• Oxidative phosphorylation.

Anabolic:
• Glycogenesis.
• (Gluconeogenesis).

Amphibolic:
• Glycolysis (anaerobic).
• Citric acid cycle (Krebs’ cycle).
 Glycolysis

1. Hexokinase or glucokinase; 2. phosphohexose isomerase; *enol-pyruvate is

3. phosphofructokinase; 4. aldolase; 5. phosphotriose isomerase; converted to
6. glyceraldehyde-3-phosphate dehydrogenase; 7. phosphoglycerate keto-pyruvate
kinase; 8. phosphoglycerate mutase; 9. enolase; 10. pyruvate kinase; spontaneously
11. lactate dehydrogenase.
 Energetics of Glycolysis
Aerobic Anaerobic
• Phosphoglycerate kinase: 2 • Phosphoglycerate kinase: 2
• Pyruvate kinase : 2 • Pyruvate kinase : 2
• 2 NADH in rx. 6 : 6 • 2 NADH in rx. 6 : 6
• ATP used in rx. 1 and 3 : -2 • ATP used in rx. 1 and 3 : -2
Net = 8 • 2 NADH used in rx. 11 : -6
Net = 2
Pyruvate Oxidation

• Pyruvate is transported
from cytosol into
mitochondrion by proton
symporter
• Oxidatively decarboxylated
to become acetyl-CoA by
pyruvate dehydrogenase
complex.
Citric Acid Cycle

Mitochondrial matrix
Energetics of Citric Acid Cycle
• 3 NADH : 9
• 1 FADH2: 2
• 1 GTP : 1
Net : 12
Oxidative Phosphorylation
• Occur at substrate level.

Previously widely accepted theory:

• When substrates are oxidized via an NAD-
linked dehydrogenase and the respiratory
chain, approx. 3 mol of Pi are incorporated
into 3 mol of 3 mol of ADP to form 3 mol
of ATP per half mol of O2 consumed.
• When a substrate is oxidized via a
flavoprotein-linked dehydrogenase, only 2
mol of ATP are formed.
Chemiosmotic Hypothesis
 Energetics of Glucose Catabolism
Aerobic Anaerobic
• Glycolysis : 8 • Glycolysis: 2
• Pyruvate oxidation: 6 Net : 2
• Citric acid cycle : 24
Net : 38

Task:
Calculate ATP production per molecule
of glucose based on latest theory!
 Gluconeogenesis
• Location: mainly in the liver and kidney.
• Function: converts non-carbohydrate
substance to glucose.
• Precursors: pyruvate derived from
– Glucogenic amino acids.
– Intermediates of TCA cycle.
– Glycerol.
– Lactate.
Cori Cycle
 Glycogen
• Location: liver (72 g) and skeletal muscle (245 g).
• Function: act as readily available source of glucose
for glycolysis.
 Hexose Monophosphate Shunt
• A.k.a. pentose phosphate pathway.
• Location: liver, adipose tissue, erythrocytes,
neutrophils, adrenal cortex, thyroid, testis,
ovaries, lactating mammary gland.
– Less active in skeletal muscle.
• Function: directly oxidizes glucose to CO2.
•Produces
NADPH.
•Produces CO2.
•No ATP is
produced.
•Increases glycolytic flux
(enzymatic level).
•Increases synthesis of
FA (transcription level).
 Uronic Acid and Hexosamines
• Uronic acid: its active derivate (UDP-
glucuronic acid) functions as precursors for
proteoglycan and other conjugation reactions.
• Hexosamines: important components of
glycoproteins, of certain glycosphingolipids,
and of glycosaminoglycans.
Fructose
Metabolis
m
Galactose Metabolism
Disorder of Carbohydrate
Metabolism
 Galactosemia
• Deficiency of galactose-1-phosphate uridyl transferase,
galactokinase, 4-epimerase.
• Signs: galactosemia and galactosuria.
– Galactitol can cause cataract.
– Pi depletion  liver failure, mental deterioration.
• Fatal in early life, but adult galactosemics tolerate
galactose because:
– Galactose-1-phosphate is converted to UDP-galactose by
UDP-galactose pyrophosphorylase.
– Galactose is converted to xylulose.
• Galactose free diet for children  control symptoms.
 Fructosemia
• Essential fructosia: deficiency of fructokinase.
– Benign, asymptomatic.
• Hereditary fructose intolerance: deficiency of
aldolase B.
– Profound hypoglycemia and vomiting after
consumption of fructose (or sucrose).
– Sequestration of Pi  ATP depletion,
hyperuricemia.
Diabetes Mellitus
Diabetic Cataract
• Its activity increases
as glucose level rises
in non insulin-
sensitive tissues (lens,
peripheral nerves,
renal glomeruli)
• Sorbitol does not
diffuse through cell
membranes 
osmotic damage.
 Hemolytic Anemia
• Deficiency of G6PD.
• Genetic.
• Common in populations of Mediterranean and
Afro-Caribbean origin.
 Essential Pentosuria
• L-xylulose appearance in urine.
• Rare hereditary disease.
• Disruption of the uronic acid pathway.

• Can give false positive results when urinary

glucose is measured using alkaline copper
reagents.

• Aminopyrine and antipyrine increase excretion of

xylulose in pentosuric acid.
 Alimentary Pentosuria
• After consumption of relatively large amounts
of fruits (e.g. pears)