19. Carbohydrate Metabolism Flashcards
Explain the pathways involved in metabolising a glucose load.
Carbohydrates are organic molecules
made up of carbon, hydrogen and oxygen.
They are consumed in the diet as
either simple sugars (glucose and fructose)
or
complex sugars (starch and cellulose).
Complex sugars are essentially
simple sugars assembled into
chains for ease of storage
(e.g. starch from plants,
glycogen from animals),
or to form structures
(e.g. cellulose in plants).
During the digestive process,
which starts in the mouth with mastication,
complex sugars are broken down
into simple sugars that
can be transported across cell walls
and used to make energy in the form of ATP.
The simple sugar glucose is the body’s
most readily available energy source
and can be used by all cells.
The main pathways in glucose metabolism are:
1 Glycolysis:
This umbrella term describes the
generation of AT P from glucose molecules.
It can be divided into three stages, which will be considered in turn:
• Glycolysis
• The Krebs cycle
• Oxidative phosphorylation and the electron transport chain
2 Gluconeogenesis:
The generation of glucose from
substrates such as pyruvate.
3
Glycogenesis:
The synthesis of glycogen
to store glucose.
4
Glycogenolysis:
The breakdown of glycogen to liberate glucose.
Glycolysis
The aim of glycolysis is to
split the 6-carbon sugar glucose
into two molecules of the
3-carbon sugar pyruvate.
This is achieved by phosphorylation
of the glucose molecule,
using the phosphate
from one AT P molecule.
Following this,
glucose-6-phosphate is converted
to fructose- 6-phosphate
(a 5-carbon sugar)
by phosphofructokinase.
This molecule is then phosphorylated again
to form fructose-1,6-bisphosphate,
using the phosphate from another AT P molecule.
This molecule is then split in two, and a series of further reactions lead to the formation of a two-pyruvate molecules (one from each half of the cleaved fructose-1,6,bisphosphate).
Two molecules of AT P are formed
as a result of the generation of each
pyruvate molecule.
So, from each molecule of glucose,
glycolysis generates
four AT Ps while two are used up,
making a net gain of two AT Ps.
Anaerobic vs aerobic respiration
When oxygen supply is inadequate,
pyruvate will enter an anaerobic
pathway.
In this pathway,
pyruvate is converted into lactate
(also called lactic acid).
Each pyruvate molecule that enters this pathway will generate one ATP and, since two pyruvates are produced from each molecule of glucose, this gives a net gain of two AT Ps from this stage of the pathway.
This is clearly not much compared to aerobic respiration, but it is better than nothing and it keeps the conversion of glucose to pyruvate going by reducing the concentration of pyruvate in the cells.
Cells that lack mitochondria,
e.g. red blood cells,
must respire anaerobically
at all times.
When the oxygen supply is adequate,
pyruvate will enter the aerobic
pathway, the Krebs cycle.
The Krebs cycle
This is also called the
citric acid cycle or the
tricarboxylic acid (TCA) cycle.
To enter the Krebs cycle, pyruvate is transported into the mitochondria where it is converted into the 2-carbon molecule, acetyl coenzyme A (acetyl CoA) by pyruvate dehydrogenase.
Acetyl CoA enters the Krebs cycle by being bound to the 4-carbon molecule oxaloacetate to form the 6-carbon molecule, citrate.
This molecule is then broken down again to a 5-carbon molecule and again to back to oxaloacetate and so on (hence the cycle…).
During this cycle,
molecules that are high in energy
are generated and each
turn of the cycle yields:
• 1 ATP
• 3 NADH (nicotinamide adenine dinucleotide. NAD+ is a coenzyme that
acts as an electron acceptor to create NADH)
• 1 FADH2 (flavin adenine dinucleotide is a redox cofactor, i.e. it undergoes
reduction-oxidation)
The cycle will turn twice for each molecule of glucose metabolised.
Oxidative phosphorylation and the electron transport chain
The electron transport chain
uses the NADH and FADH2 generated
in the Krebs cycle to make AT P.
In a series of enzymatic reactions
that occur at the
inner mitochondrial membrane,
electrons from NADH and FAD2
are transferred repeatedly
from donor (e.g. NADH) to acceptor (e.g. oxygen)
molecules further down the ‘chain’.
This process is coupled with the transfer of H+ ions across the inner mitochondrial membrane and this sets up a concentration gradient across the membrane.
H+ ions then flow back across
the membrane through
AT P synthase channels
and in doing so supply the
energy needed to
phosphorylate ADP to produce AT P.
When they come to the end
of the electron transport chain,
the electrons are accepted by oxygen molecules,
which go on to combine
with H+ ions to
form water.
Without oxygen, the electrons
cannot keep being passed down
the chain and respiration ceases.
For each molecule of glucose,
the electron transport chain yields 34 ATP.
Gluconeogenesis
Gluconeogenesis describes the synthesis of glucose from: • Pyruvate • Lactate • Glycerol • Alanine and glutamine (amino acids)
This process exists in case the
supply of dietary glucose runs out.
The brain preferentially uses glucose
as its fuel source,
although it can use ketones
to some degree,
and so it is vital that there
are alternative sources of this substrate.
Gluconeogenesis takes place
mainly in the liver, and
to a small extent,
in the kidneys.
Turning pyruvate into glucose is not simply the reverse of glycolysis, instead pyruvate (3-carbon) is converted to oxaloacetate (4-carbon) at the expense of one AT P molecule.
From here oxaloacetate is
converted to phosphoenolpyruvate
by the enzyme phosphoenolpyruvate
carboxykinase,
and from then a series of
reactions generate glucose.
The net cost of synthesising glucose
from pyruvate is 6 AT Ps, but these
glucose can then be fed back
into the glycolysis pathway to yield 36 AT Ps.
Lactate
Lactate produced in times of anaerobic respiration, can be converted into pyruvate and back to glucose in the liver in the Cori cycle (also called the lactic acid cycle).
Lactate can be used as a substrate by some tissues.
Amino acids
Amino acids can provide a
source of energy because
during the process of
their metabolism many
intermediary products are
formed and broken down
and many of these can
be fed into the Krebs cycle,
e.g. pyruvate, acetyl CoA,
oxaloacetate, α ketoglutarate,
to yield AT P.
This fuel source becomes more
significant during starvation,
when muscle will be broken down to fuel respiration.
Glycerol
Glycerol is liberated when
triglycerides (fat) are hydrolysed
to fatty acids and glycerol.
These fatty acids then undergo
β oxidation into acetyl CoA,
which is fed into the Krebs cycle.
The glycerol released is fed directly
into the Krebs cycle as
dihydroxyacetone phosphate.
Fat yields approximately 9 kcal/g
compared to 4 kcal/g from carbohydrate
though the process of liberating the
energy is much slower.
Even very slim people have
significant fat reserves,
which will act as an energy source
when carbohydrates are exhausted.
Glycogenesis
Glycogenesis
Glucose is stored as the multi-branched polysaccharide glycogen, primarily
in the liver and muscles.
Glycogenesis occurs when glucose
and AT P are present in relatively high amounts
as it uses up one AT P molecule for every
glucose molecule incorporated into the chain.
Glucose is stored in glycogen
as glucose-6-phosphate.
Glycogenolysis
Glycogenolysis
Glycogen is broken down to
release glucose during glycogenolysis.
This process involves the
removal of glucose monomers
from the storage chain
by phosphorylation.
The reaction is catalysed by
glycogen phosphorylase.
A series of further steps result in
glucose-6-phosphate being fed into the
glycolysis pathway.
Glycogen stored in the liver
is broken down by glycolysis,
which releases glucose into
the blood for utilisation by other cells,
while that present in the
skeletal muscle provides an
immediate energy source for muscle contraction.
Glycogen provides a source of energy that can be mobilised instantly.
However, it is limited and, during intense exercise, the store will be
exhausted in around 3–4 hours.
Regulation of glycogen synthesis
Regulation of glycogen synthesis is reciprocal.
The following act via
G-protein-coupled receptors
to exert their effects:
• Adrenaline – stimulates glycolysis
• Glucagon – stimulates glycolysis
and inhibits glycogenesis
• Insulin – inhibits glycolysis
and stimulates glycogenesis
