Course Requirements
• Required Texts:
– Biochemistry, Campbell and Farrell, 6th edition.
Publisher 2008
– Lippincott’s Illustrated Reviews Biochemistry, 4th
edition. Publisher 2008
The study of carbohydrates and
lipids metabolism
• I-Introduction:
– Definition
• metabolism of carbohydrates
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Digestion of carbohydrates
Glycolysis
Tricarboxylic acid cycle
Glycogen metabolism
Gluconeogensis
Pentose phosphate pathway and NADPH
Metabolism of monosaccharides and disaccharides
Lipids metabolism
– Digestion of dietary lipids
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•
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How fats are digested in animals
How fats are mobilized and transported in tissues
How fats are oxidized
How “ketone bodies” are produced
– Fatty acid and triacylglycerol metabolism
– Biosynthesis of Complex lipid metabolism
– Biosynthesis Cholesterol and steroidhormones
Bioc 211
General metabolism
http://www.runningforfitness.org/book/chapter-7-eating-drinking-andrunning/energy-while-running
How the body converts food to
energy?
• We are going to look at two major questions
in biochemistry
– How do cells extract energy from their
environment?
– How do cells synthesis the building blocks of
their macromolecules?
• This leads to the study of ..........
Introduction to Metabolism
Campbell’ Chapter 15, P417
The nature of Metabolism
• Metabolism: the chemical reactions of biomolecules, the
sum total of all biochemical reactions that take place in an
organism . It is the biochemical basis of life processes
• Characters
– Catalyzed by a specific enzyme
• Each reaction require a specific enzyme
– Typically occur in pathways ( in a sequence)
• Several reactions in a row
– Two major groups
• Catabolism: the breakdown of complex substances Usually energyyielding!.
• Anabolism: the synthesis of complex substances needed by cells from
simpler ones such as DNA Usually energy-requiring!.
Major purpose
• living things require energy for:
2- Synthesis of
biomolecules and
simple precursors
3- Active transport
of molecules and
ions
1- Mechanical
work in muscle
contraction and
other cellular
movement
What carries this energy??????
• The energy currency or
coin of the cell is
• Energy rich molecules
triphosphate contains 2
phosphoanhydride
bonds
The 2 phosphate
bonds
(phosphoanhydride
bond) is here the
energy is stored in
ATP
The energy
• A large amount of energy
is liberated when
– ATP → ADP + Pi
(orthophosphate)
– ATP → AMP + PPi
(pyrophosphate)
• The free energy liberated
with the hydrolysis of ATP
is used to drive reactions
that require input of free
energy
The energy
• ATP is continuously formed and consumed
• It’s the principal immediate donor and not
long term storage of energy
• Rate of turnover of ATP is high. A molecule of
ATP is consumed within a minute it is formed
• Resting person consumes 40 kg of ATP / 24hr
How do cells make ATP?
• By phosphorylation... adding a phosphate to ADP
ADP
+
P
- - - - - ->
ATP
• 3 mechanisms of phosphorylation:
– Substrate level phosphorylation ( where a substrate
molecule (X-P) donates its high energy P to ADP making ATP)
– Oxidative phosphorylation (e- transferred from organic
molecules and passed through a series of acceptors to O2)
– Photophosphorylation ( occurs during photosynthesislight energy used to make ATP)
Electron carriers
• When food molecule oxidized – electrons are removes
• These electrons are carried to oxygen
e-
How does the e- get to
oxygen??????
O2
Answers: electron carriers
• NAD+/ FAD
• Reduced form with electrons bound is NADH/ FADH2
• NADH/ FADH2 transfer e- to O2 in the mitochondria by
means of ETC ( ATP generated in this process)
The nature of Metabolism
• Complex substances are broken down for
energy, required metabolites, structural
components, etc.
• Cells must synthesize new complex
substances.
• Thousands of such reactions are occurring
simultaneously in a single cell.
The nature of Metabolism (cont’d)
• These rxns occur with a minimum of side
products, energy loss or undesired
interferences and at reasonable temperatures,
pH and pressure.
• All of these rxns must be controlled or
regulated for optimum efficiency.
Free Energy Changes in Metabolism
• Overall G is negative (-) for catabolic
processes
• For an anabolic process, the G ought to be
positive (+)
• So generally catabolic processes generate
energy for anabolic processes
General Principles:
• Metabolic pathways are irreversible (because
they must be regulated)
• Metabolic pathways have (first) committed
step
• Metabolic pathways are regulated
• Metabolic pathways are compartmentalized
Principles (cont’d):
• Metabolic reactions are often reversible
• Processes of metabolism are highly
controlled:
– Anabolism and catabolism are not usually
balanced - one or the other may predominate
in certain cells or at different times depending
on cell needs
– The pathway to synthesize a complex
substance is not simply the reverse of the
degradative pathway.
Principles (cont’d):
• Metabolic pathways are compartmentalized
• Cytosol (glycolysis, fatty acid biosynthesis,
pentose phosphate cycle)
• Mitochondria (TCA cycle, OxPhos, fatty acid
oxidation, amino acid breakdown)
• Nucleus (DNA replication, transcription, RNA
processing)
• ER
– Rough ER: synthesis of membrane and secretory proteins
– smooth ER: lipid and steroid biosynthesis
• Golgi (posttranslational processing of proteins)
Catabolism
• catabolism: the breakdown of larger molecules into
smaller ones; an oxidative process that releases energy
– Breakdown of monomers to common intermediates,
and thus to CO2 and electrons is accomplished
through a central oxidative pathway:
• The Citric Acid Cycle or TCA or the Krebs Cycle.
• This cycle leads to the production of ATP by
processes called electron transport and oxidative
phosphorylation.
Catabolism
Proteins
Amino acids
polysaccharides
Glucose/other
sugars
lipids
Glycerol/fatty
acids
Pyruvate
NH4+
Acetyl CoA
Citric acid cycle →ETS/OxPhos →ATP
Co2
Oxidative processes produce ATP &
NADH for energy
Anabolism
• Anabolism: the synthesis of larger molecules from
smaller ones; a reductive process that requires energy
– utilization of critical Common intermediates including
components of TCA cycle to make building blocks
• Making building block requires energy = ATP
• Synthesis of macromolecules requires energy =
ATP
• note CO2 not generally reused
Proteins
Amino acids
Polysaccharides
Glucose/other
sugars
Lipids
Glycerol/fatty
acids
Pyruvate
NH4+
Acetyl CoA
Citric acid cycle
Co2
Anabolism
Intermediates
Summary
• In catabolism, large molecules are broken down
to smaller products, releasing energy and
transferring electrons to acceptor molecules of
various sorts. The overall process is one of
oxidation.
• In anabolism, small molecules react to give rise
to larger ones; this process requires energy and
involves acceptance of electrons from a variety of
donors. The overall process is one of reduction
A Comparison of Catabolism and Anabolism
• Metabolism is the sum total of the chemical
reactions of biomolecules in an organism
Anabolic vs catabolic reactions
Anabolism
Synthesis reactions
Catabolism
Degradation reactions
General description
Building of a large molecule
(polymer) from smaller
building blocks (monomer):
A + B → A--B
Breakdown of polymer into
individual monomers:
C—D → C + D
Descriptive terms
Building, constructive,
anabolic
Breakdown, digestive,
decomposition, catabolic
Bond
formed
broken
Energy
Energy is required (=
Endergonic)
Energy is released (=
Exergonic)
Water
Water is released (=
Dehydration)
Water is required (=
Hydrolysis)
Example
Building a protein from
individual amino acids;
Building a triglyceride from
glycerol and 3 fatty acids, etc
Breaking a protein into
individual amino acids;
Breaking starch down into
monosaccharides, etc.
General Pathways of Metabolism
Breakdown of macromolecules to building
blocks generally hydrolytic
Large units of the cell
M
e
t
a
b
o
li
s
m
I
polysaccharides
Building blocks of the cell
Glucose, other sugars
Lipid membranes
Fatty Acids/ Glycerol
proteins
Amino Acids
Nucleic acids
Nucleotides
M
e
t
a
b
o
li
s
m
II
Metabolism
Energy-containing nutrients are
processed in three major stages:
1. Digestion – breakdown of food;
nutrients are transported to tissues
2. Anabolism and formation of
catabolic intermediates where
nutrients are:
- Built into lipids, proteins, and
glycogen or
- Broken down by catabolic pathways
to pyruvic acid and acetyl CoA.
3. Oxidative breakdown – nutrients
are catabolized to carbon dioxide,
water, and ATP
Summarize
• Define metabolism
• Distinguish between anabolism and
catabolism
Digestion of carbohydrates
Lippincott’s chapter 7, P86
The digestive system
Prepares food for use by all body cells
The digestive process involves a series
of physical and chemical actions that
break down the components of food
into nutrient particles small enough
for absorption
Digestion of Carbohydrates
• The principle site of carbohydrates digestion are
the mouth and small intestine
• The dietary carbohydrate consist of:
– Polysaccharides: starch glycogen and cellulose
– Disaccharides: maltose, sucrose and lactose
– Monosaccharides: mainly glucose and fructose
• No need for monosaccharides digestion prior to
absorption, whereas di/polysaccharides must be
hydrolysed to simple sugars before their
absorption
Digestion of Carbohydrates
• In the mouth - Chewing
increases surface area of
food allowing salivary αamylase to begin
digestion of starch:
• Some of the free glucose
in food can be absorbed
through lining of the
mouth
Digestion of Carbohydrates
• In the stomach –
– Carbohydrates digestion
halts temporarily in the
stomach
– Salivary amylase is
inactivated by stomach
high acidity.
Digestion of Carbohydrates
• In the small intestine - the
stomach contents are neutralised
by pancreatic juice.
– Pancreatic amylase continues
digestion of starch to
oligosaccharides and maltose.
– Intestinal brush border membrane
enzymes
• Maltase hydrolyses maltose to
glucose.
• Sucrase hydrolyses sucrose to
glucose + fructose
• Lactase hydrolyses lactose to glucose
+ galactose
– The end product of carbohydrates
digestion are glucose which are
readily absorbed through the
intestinal mucosal cells into the
blood stream
Digestion of Carbohydrates
• In the Large intestine
– Humans do not produce
and secrete β-(1-4)
endoglucosidase in
digestive juice
• Humans unable to digest
cellulose
• undigested fibre is attacked
by bacteria (generates
bowel gas).
• Fibre aids intestinal
motility and acts as a softer
• Fibre is eventually excreted
Absorption of monosaccharides by
intestinal mucosal cells
• Different sugars have different mechanisms of
absorption:
– Glucose & galactose actively taken up by mucosal cells
energy dependent secondary active transport (by Na+ pump).
– Fructose is taken up by facilitative transport down
concentration gradient via passive carrier mediated transport.
• Adsorbed sugars diffuse from intestinal mucosal
cell into portal circulation and are transported to
the liver.
Absorption of monosaccharides by
intestinal mucosal cells
Abnormal degradation of
disaccharides
•
•
•
•
•
Hereditary deficiency
Mal nutrition
Drug injure the mucosa of the small
intestine
Lactose Intolerance - reduction in
amount of lactase produced
(common in Asians & Africans).
Lactose is not hydrolysed but enters
the large intestine and draws water in
by osmosis which causes diarrhoea.
Lactose is metabolised by bacteria
generating CO2 and H2. Milk products
need to be avoided.
Sucrose Intolerance - reduction in
amount of sucrase produced.
Symptoms similar to lactose
intolerance (found in 10% of
Greenland Eskimos).
Metabolic fate of carbohydrates
• After being absorbed from the
intestinal tract the
monosaccharides are carried by
the portal circulation to the liver
– In the liver D-glucose
phosphorylated to G-6-P
– D-fructose and D-galactose are
phosphorylated to and convert to
glucose in the liver
– G-6-P is an intermediate in several
metabolic pathway that use
glucose in the liver
– Depending on the supply and
demand includes
•
•
•
•
•
Glycolysis
Glycogenesis
Glycogenlysis
Gluconeogenesis
Pentose phosphate pathway
Metabolic fate of carbohydrates
Carbohydrate
Metabolism
Overview
Glycogen
Glycogenesis
Pentose
Glycogenlysis
Glucose
Gluconeogenesis
PPP
other
sugars
Glycolysis
Pyruvate
Lactate
Acetyl CoA
Citric acid cycle→ATP
EtOH
Summary
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•
•
•
•
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•
•
Salivary α-amylase acts on dietary polysaccharides (glycogen, amylose,
amylopectin), producing oligosaccharides.
Pancreatic α-amylase continues the process of polysaccharide digestion.
The final digestive processes occur at the mucosal lining of the small intestine.
Several disaccharidases [for example, lactase (β-galactosidase), sucrase, maltase,
and isomaltase] produce monosaccharides (glucose, galactose, and fructose).
These enzymes are secreted by and remain associated with the luminal side of the
brush border membranes of intestinal mucosal cells.
Absorption of the monosaccharides requires specific transporters.
If carbohydrate degradation is deficient (as a result of heredity, intestinal disease,
malnutrition, or drugs that injure the mucosa of the small intestine), undigested
carbohydrate will pass into the large intestine, where it can cause osmotic
diarrhea.
Bacterial fermentation of the compounds produces large volumes of CO2 and H2
gas, causing abdominal cramps, diarrhea, and flatulence.
Lactose intolerance, caused by a lack of lactase, is by far the most common of
these deficiencies.
Summarize
Q 1T/F
• The enzyme α–amylase:
1.
2.
3.
4.
5.
Hydrolyses glycogen to give glucose and maltose
Is present in saliva
Is activated by trypsin in the small intestine
Hydrolyses cellulose to glucose and maltose
If absent from pancreatic secretion, results in
incomplete digestion of starch, a large bacterial
population in the faeces and diarrhoea
A 1 T/F
• The enzyme α–amylase:
1. Hydrolyses glycogen to give glucose and maltose
(T)
2. Is present in saliva (T)
3. Is activated by trypsin in the small intestine (F)
4. Hydrolyses cellulose to glucose and maltose (F)
5. If ibsent from pancreatic secretion, results in
incomplete digestion of starch, a large bacterial
population in the faeces and diarrhoea (T)
Q2 T/F
• The absorption of glucose in the digestive
tract:
1.
2.
3.
4.
Occurs in the small intestine
Is an energy-requiring process
Is stimulated by the hormone glucagon
Occurs more rapidly than the absorbtion of any
other sugar
5. Is impaired in cases of diabetes mellitus
A 2 T/F
• The absorption of glucose in the digestive
tract:
1.
2.
3.
4.
Occurs in the small intestine (T)
Is an energy-requiring process (T)
Is stimulated by the hormone glucagon (F)
Occurs more rapidly than the absorbtion of any
other sugar (F)
5. Is impaired in cases of diabetes mellitus (F)
Q 3 T/F
• Diasaccharides in the diet, or those formed
from polysaccharide digestion:
1. Are absorbed as such by the small intestine
2. Are hydrolysed to constituent monosaccharides
by enzymes present in pancreatic juice
3. Are hydrolysed by specific enzymes of the small
intestine
4. Are quantitatively unimportant since there are
no enzyme deficiency diseases associated with
their metabolism
A 3 T/F
• Diasaccharides in the diet, or those formed
from polysaccharide digestion:
1. Are absorbed as such by the small intestine (F)
2. Are hydrolysed to constituent monosaccharides
by enzymes present in pancreatic juice (F)
3. Are hydrolysed by specific enzymes of the small
intestine (T)
4. Are quantitatively unimportant since there are
no enzyme deficiency diseases associated with
their metabolism (F)