2. Metabolism
- Metabolism: the reactions proceeding inside the body
which involve synthesis, conversion & breakdown of various
substances or compounds.
- The substances which are subjected to the metabolism
process are called metabolites.
- The metabolism comprises 2 essential processes:
a) Anabolism: (synthesis). It involves the various synthetic
(anabolic) processes in which the metabolites are
utilized.
b) Catabolism: (breakdown). It involves the various
breakdown (catabolic) reactions to which the
metabolites are subjected (usually oxidative pathways).
- The most important aim of these oxidative pathways is
energy production.
3. 1. Digestion of carbohydrates
1.1 Introduction: More than 60% of our foods are
carbohydrates.
A. Starch, glycogen, sucrose, lactose and cellulose are the chief
carbohydrates in our food.
B. Before intestinal absorption, they are hydrolyzed to
monosaccharides (glucose, galactose and fructose) except
cellulose?
C. A family of glycosidases that hydrolyzes carbohydrate into
their monosaccharide components catalyzes hydrolysis of
glycosidic bonds.
Carbohydrate metabolism
4. I. Digestion of carbohydrate
1- In the mouth by (salivary α–amylase = ptyalin) (pH is 6.8)
Cooked starch → maltose, isomaltose and starch dextrins.
2- In the stomach:
Carbohydrate digestion stops temporarily
due to the high acidity, which inactivates the
salivary α-amylase.
3- Digestion of carbohydrate by pancreatic α-
amylase in the small intestine:
Its optimum pH is 7.1
It acts on cooked and uncooked starch, hydrolyzing
them into maltose and isomaltose.
- What about cellulose?
5. 4- Final carbohydrate digestion by intestinal enzymes:
A. By several disaccharidases (secreted through and remain
associated with the brush border of the intestinal mucosal
cells).
B. The disaccharidases include:
1- Lactase (β-galactosidase) which hydrolyses lactose:
Lactose Lactase→ Glucose + Galactose
2- Maltase (α-glucosidase), which hydrolyses maltose:
Maltose Maltase→ Glucose + Glucose
3- Sucrase (α-fructofuranosidase), which hydrolyses sucrose:
Sucrose Sucrase → Glucose + Fructose
4. Isomaltase (α-dextrinase), which hydrolyzes the (1,6) linkage of
isomaltose: Isomaltose Isomaltase → Glucose + Glucose
6.
7. II. Absorption
A. The end products of carbohydrate digestion are
monosaccharides: glucose, galactose and fructose. They
are absorbed from the jejunum to portal veins to the liver,
where fructose and galactose are transformed into
glucose.
B. Two mechanisms are responsible for absorption of
monosaccharides:
- Active transport (against concentration gradient i.e. from
low to high concentration). For glucose & galactose.
- Rapid, (by SGLT-1), absorbed with Na+ and consumes
ATP.
- Passive transport (by facilitated diffusion): No need for
energy, slow, from high concentration to low
concentration. (by GLUT-5). E.g. Fructose.
8.
9. Fate of absorbed sugars:
A. Uptake by liver:
After absorption, the liver takes up sugars, where galactose and fructose
are converted into glucose.
B. Glucose utilization by tissues:
Glucose may undergo one of the following fate:
1. Oxidation: through
a) Major pathways (glycolysis and Krebs cycle) mainly for production
of energy + H2O + CO2.
b) Pentose phosphate pathway (HMP): for production of pentoses and
NADPH + H+.
c) Uronic acid pathway: for production of glucuronic acid.
10. 2. Storage in the form of:
a) Glycogen: by glycogenesis.
b) Fat: by lipogenesis.
Conversion to substances of biological importance (example):
a) Ribose, deoxyribose → RNA and DNA.
b) Lactose → milk.
c) Glucosamine and galactosamine → mucopolysaccharide.
d) Glucuronic acid → glycosaminoglycans and mucopolysaccharide.
e) Fructose → in semen.
f) Synthesis of non essential amino acids from glucose intermediates.
Fate of absorbed sugars: cont…
12. Glucose importance
• Biochemically, glucose is the most important
carbohydrates:
• Glucose is the bulk of dietary carbohydrates
• Glucose is the bulk of absorbed carbohydrates
• Most carbohydrates in diet are converted into
glucose in the liver.
• Glucose is the major fuel of human tissues.
• Glucose is the universal fuel of the fetus.
13. 1. Glycolysis (Embden-Meyerhof Pathway):
Definition:
1. Glycolysis means oxidation of glucose to give pyruvate (in
the presence of oxygen), or lactate (in the absence of oxygen).
site:
1. Intracellular location: cytosol.
2. Organ location: all tissue cells, but it is of physiological
importance in:
a) Tissues with no mitochondria: e.g. mature RBCs.
b) Tissues with few mitochondria: e.g. Testes and leucocytes.
c) Tissues undergo frequent oxygen lack: skeletal muscles
especially during exercise.
Glucose oxidation
major pathway
14. Stages of glycolysis:
Glycolysis has 2 phases (10 reactions):
1. Stage one: (C6) Preparatory phase (the energy requiring
stage) (5 reactions):
a) One molecule of glucose (C6) is converted into two
molecules of glyceraldehyde-3-phosphate (2 C3).
b) These steps requires 2 molecules of ATP (energy loss).
2. Stage two: (C3) Payoff phase (the energy producing stage)
(5 reactions):
a) The 2 molecules of glyceraldehyde-3-phosphate are
converted into 2 pyruvate molecules (aerobic glycolysis) or 2
lactate molecules (anaerobic glycolysis).
b) These steps produce ATP molecules (energy production).
15. • Stage 1: Preparatory phase
• 2 ATP are consumed, 1 glucose molecule → 2 glyceraldehyde 3-P
Mg2+
Mg2+
+ H2O
+ H2O
or glucokinase
17. Energy produced in glycolysis
When one mole of glucose
is oxidized:
ATP lost:
- 1 ATP in reaction 1
- 1 ATP in reaction 3
(Total= 2 ATP are lost)
b) ATP gained:
In the absence of Oxygen:
- 2 ATP in reaction 7
- 2 ATP in reaction 10
(Total= 4 ATP are gained)
4 ATP – 2 ATP = 2 ATP X 10000
= 20000 calories
18. • In the presence of Oxygen:
- 2 X 3 ATP in reaction 6
(NAD+ → NADH+H)
- 2 ATP in reaction 7
- 2 ATP in reaction 10
(Total= 10 ATP are gained)
10 ATP – 2 ATP (lost) = 8 ATP X 10000 ≈ 80000 calories
Each high energy phosphate bond in ATP contains 7000-13000
calories (Average 10000).
- According to the tissue = (6-8 ATP ≈ 60000-80000 calories)
- In liver, kidney & cardiac muscles: NADH (c) → NADH (m) → 3ATP
- In cells of skeletal muscles & brain: NADH (c) → FADH2 (m) → 2ATP
(according to the shuttle when it enters into mitochondria).
So, under the aerobic conditions, the net energy yielded is 6-8 ATP.
Energy produced in
glycolysis cont…
19. Fate of pyruvate & NADH
1. Glycolysis under aerobic
conditions:
- Pyruvate will enter mitochondria
and undergoes oxidative
decarboxylation to Acetyl CoA & CO2
- The tow molecules of NADH+H+
will be converted to 2 or 3 ATP in
mitochondria by oxidative
phosphorylation.
2. Glycolysis under anaerobic
conditions:
- Pyruvate will be converted to Lactic
acid by (LDH) Lactate dehydrogenase
enzyme with consumption of
NADH+H+ (from reaction No 6).
Pyruvate LDH (absent O2)→ Lactic acid
NADH+H+ →NAD+
What happens in yeasts? fermentation
Why you get
muscle pain the
2nd day after
you have severe
exercise?
20. Importance of glycolysis
1. An important source of energy for cells (6-8 ATP in ↑O2, 2 ATP on
↓O2/ glucose molecule).
2. It provides the cell with pyruvic acid for initiation of Krebs cycle.
3. It makes oxygenation for tissues through 2,3 BPG in RBCs (1,3 BPG
→ 2,3 BPG).
4. It connects between COH & fat metabolism through G3P.
5. It provides the 3 Phosphoglycerate for the synthesis of AA; serine,
and the Pyruvate for synthesis of AA; alanine.
6. Its reversibility is an essential part of gluconeogenesis.
7. It is an emergency energy-yielding pathway for cells in the absence
of O2.
8. It is a major pathway for ATP in tissues lacking mitochondria (eg.
RBCs, cornea, lens, etc.)
9. It is a significant pathway for ATP in tissues having few mitochondria
(eg. WBCs, testes, kidney medulla, etc.)
10. It is very essential for brain which depends on glucose for energy.
22. Clinical aspects of glycolysis:
1. Pyruvate kinase (PK) deficiency:
Genetic deficiency of PK enzyme leads to ↓ rate of glycolysis & ATP
→ excessive hemolysis of RBCs leading to hemolytic anemia.
2. Hexokinase deficiency:
It leads to hemolytic anemia due to decrease ATP production.
The mechanism is similar to that of PK deficiency.
3. Lactic acidosis:
It is the lowered blood pH and bicarbonate levels due to increased
blood lactate above normal level. It may lead to coma.
Causes of lactic acidosis:
1- Increased formation of lactate as in severe muscular exercises.
2- Decreased utilization of lactate in tissues: it occurs in cases of
anoxia, hypoxia e.g. myocardial infarction, shock, respiratory disorders,
alcohol abuse and anemia.
