Carbohydrate Metabolism Flashcards
Carbohydrate Summary
Large group of molecules that all have similar atomic
compositions but differ greatly in size, chemical
properties, and biological functions.
Formula C𝑛(H2O)𝑚, (n and m stand for numbers), which
makes them appear as “hydrates of carbon”
Carbohydrates are not really “hydrates” because the
water molecules are not intact. Rather, the linked carbon
atoms are bonded with hydrogen atoms (—H)and
hydroxyl groups (—OH), the components of water.
Carbohydrates have 4 majorroles
They are a source of stored energy that can be
released in a form usable by organisms.
They are used to transport stored energy
within complex organisms.
They serve as carbon skeletons that can be
rearranged to form new molecules.
They form extracellular assemblies such as
cell walls that provide structure to organisms.
4 categories, defined by the number of monomers
Monosaccharides (mono, “one,” + saccharide, “sugar”), such
as glucose, are simple sugars. They are the monomers from
which the larger carbohydrates are constructed.
Disaccharides (di, “two”) consist of two monosaccharides
linked together by covalent bonds. The most familiar is sucrose, which is made up of covalently bonded glucose and fructose molecules.
Oligosaccharides (oligo, “several”) are made up of several (3–
20) monosaccharides.
Polysaccharides (poly, “many”), such as starch, glycogen, and
cellulose, are polymers made up of hundreds or thousands ofmonosaccharides.
Monosaccharide
- Glucose = the blood sugar → energy
- Straight chains or ring
- Ring predominates biologically as its more table in water
- 2 forms of glucose ring = α and β – differ in OH and H orientation
on C1. Forms interconvert when dissolved in water and exist in equilibrium
Different monosaccharides
have different numbers of
Carbon - Can be 3 - 8
- Pentose – 5 carbons
- Hexose – 6 carbons
- Bonded by a condensation reaction that forms a
glycosidic bonds - 2 bonded monosaccharides = 1 disaccharide
Polysaccharide
Large polymers of
monosaccharides,
connected by glycosidic
bonds
Not necessarily linear
chains, branching possible
Starch
- Polysaccharides of glucose with α-glycosidic bonds
(α-1,4 and α-1,6 glycosidic bonds) - Different starches can be distinguished by the
amount of branching that occurs at carbons 1 and 6 - Principal energy storage compound of plants
- Some plant starches, such as amylose, are
unbranched; others are moderately branched (for
example, amylopectin)
Cellulose
- Predominant component of plant cell walls
- Most abundant organic compound on Earth
- Like starch and glycogen, cellulose is a
polysaccharide of glucose, but its individual
monosaccharides are connected by β- rather than by
α-glycosidic bonds (chemically more stable than
starch). - Cellulose is an excellent structural material that can
withstand harsh environmental conditions
Glycogen
- Water-insoluble, highly branched polymer of glucose
- Used to store glucose in the liver and muscles and is
thus an energy storage compound for animals - Glycogen and starch are readily hydrolyzed into
glucose monomers, which in turn can be broken down
to liberate their stored energy.
Digestion of Carbohydrates
➢Mouth: salivary amylase (a1-4 bonds in starch)
➢Stomach: no carbohydrate digestion
➢Duodenum: pancreatic amylase
➢Jejunum: final digestion by cell surface
enzymes eg. isomaltase (1-6 bonds),
glucoamylase, sucrase & lactase
- Main monosaccharides: Glu, Gal, Fru
➢Absorbed into intestinal cells: - Glu - uses Na+- ATP pump ( absorb against conc. gradient)
- Gal - also energy driven
- Fru - probably diffusion
Pancreas
- 2% Islets of Langerhans
- Act an endocrine gland
- Secretes various hormones that
regulate blood glucose levels. - The endocrine cells are clustered
together, forming the so-called
islets of Langerhans. - Small,
- Round-shaped
- Scattered throughout the
exocrine pancreatic tissue
When glucose levels are HIGH
- Insulin is released from beta (β)
cells → decrease in blood glucose
concentration. - This may involve:
- stimulating glycogen
synthesis in the liver
(glycogenesis), - promoting glucose uptake by
the liver and adipose tissue, - increasing the rate of glucose
breakdown (by increasing cell
respiration rates)
When glucose levels are LOW
- Glucagon is released from alpha
(α) cells → increase in blood
glucose. - This may involve:
- stimulating glycogen
breakdown in the liver
(glycogenolysis), - promote glucose release by
the liver and adipose tissue, - decreasing the rate of
glucose breakdown (by
reducing cell respiration
rates)
Glycogenesis
- Glycogen - highly branched
polymer of glucose (storage) - Genesis – formation
- Insulin stimulates glycogenesis
- Insulin inhibits glycogen
breakdown - Fed state
Glycogenesis
1. Glucose phosphorylation
Conversion of glucose to G-6-P
glucokinase (liver) and hexokinase
(muscle).
2. Conversion of G-6-P to G-1-P
Transfer of the phosphate group from
C6 to C1 by enzyme
phosphoglucomutase
3. Glucose activation
G1P reacts with high energy nucleotide
uridine triphosphate (UTP) to give
uridine diphosphate glucose (UDPG).
Enzyme: G1P uridyltransferase
Glycogenesis
4. Glucose addition to the
polymer backbone
UDPG-activated glucose is
transferred to preexisting
glycogen. Catalysed by
glycogen synthase.
Glycogenesis
5. Branch formation
When 10 or more glycose in a
chain, branching enzyme cuts a
terminal segment of at least 6
glucose molecules and inserts it
with an α 1 → 6 glycosidic bond on a
neighbouring chain
Glycogenolysis
- Glycogen - highly branched polymer of glucose (storage)
- Lysis – breakdown
- Not exact opposite of glycogenesis due to irreversible reactions
- Between meals, the liver breaks down glycogen and releases free
glucose to the bloodstream. - In contrast, glycogen serves as an energy reserve that can be
rapidly mobilized to fuel contraction in muscle cells. Muscle does
not release glucose to the circulation, its glycogen stores are
exclusively used in that tissue.
Glycogenolysis
1. Glycogen phosphorylation - Glycogen degradation initiated by
phosphorylase. Acts on the
nonreducing ends of glycogen
branches, releasing glucose-1-
phosphate. Action stops 4
glucose residues before an α 1 →
6 junction. - Oligoα (1,4)α (1,4)-
glucantransferase, separates a
trisaccharide from the terminal
branch and transfers it to the end
of a neighbour branch, where it is
attached via a α 1 → 4 bond.
- Hydrolysis of α 1 → 6
glycosidic bonds
Debranching enzyme
releases free glucose - G-6-P formation
G-1-P converted to G-6-P by
phosphoglucomutase (reverse
reaction in glycogenesis) - Free glucose formation
Hydrolysis of G-6-P to glucose
catalysed by glucose-6-
phosphatase (glucokinase in
glygogenesis)
Glycolysis
- Glucose → 2 x pyruvate
- AKA Embden - Meyerhof - Parnas
Pathway - In MOs, metabolism of glucose and
other monosaccharides is through
fermentation → lactate, ethanol, acetic
acid and CO2
1. Formation of G-6-P - Phosphorylation at carbon 6
- The reactions necessary to obtain
G-6-P are different depending on
the starting material (glucose or
glycogen)
2. Formation of fructose-
6-phosphate (F-6-P) - Reversible reaction
- Catalysed by
phosphoglucoisomerase (PGI),
which requires Mg 2+ or Mn 2+. - F-6-P is phosphorylated at carbon 1
- Requires the transfer of a
phosphoryl group from ATP - Catalysed by phosphofructokinase
(PFK) in the presence of Mg 2+ ions
3. F-6-P phosphorylation - Fructose-1,6bisphosphate is cleaved into
two triosephosphate molecules:
glyceraldehyde-3phosphate (G3P) and
DHAP. - Reversible reaction
- Catalysed by aldolase, a lyase.
4. Triose-phosphates formation
5. Triose-phosphate Interconversion - Reversible conversion of
DHAP into G3P, catalysed
by triose-phosphate
isomerase (TPI). - Glyceraldehyde is dehydrogenated
- Phosphate (Pi ) added to form 1,3-
bisphosphoglycerate - Glyceraldehyde-3-phosphate
dehydrogenase (G3PDH), an
oxidoreductase
6. Glyceraldehyde-3-phosphate
oxidation and phosphorylation - Phosphate is transferred
from 1,3-
bisphosphoglycerate to ADP - Catalysed by
phosphoglycerate kinase
7. Substrate-level phosphorylation - 3-Phosphoglycerate is converted
into 2-phosphoglycerate - Reversible reaction
- Catalysed by phosphoglycerate
mutase, requires Mg 2+
8. Phosphoglycerate formation - Dehydration of 2-
phosphoglycerate - Enolase requires Mg 2+ or
Mn 2+
9. Formation of phosphoenolpyruvate - Transfer a phosphate molecule to ADP,
forming ATP - Catalysed by pyruvate kinase
- Requires Mg 2+ or Mn 2+ ions
- Potassium ion is an activator of the
enzyme - Enolpyruvate intermediate
10. Second substrate-level phosphorylation
Glycolysis Summary
For each glucose molecule
entering the reaction: - 2 molecules of ATP are used
- 4 molecules of ATP are produced.
- Net gain of 2 ATP molecules
- 2 molecules of reduced NAD are
produced - Glucose is converted to 2
molecules of pyruvate
Ethanol Formation
Energy generating process used under anaerobic
conditions by yeast that allows re-oxidation of
NADH, resulting in ethanol and CO2 production.
Glucose + 2 ADP → 2 EtOH + 2 ATP + 2 CO2
Lactate Formation
- Anaerobic conditions
- Pyruvate is reduced to lactate by
lactate dehydrogenase, an enzyme
that uses NAD as a coenzyme. - Reversible
- Skeletal muscle during intense
exercise
Warburg Effect
- Otto Warburg observed that tumour slices
consume glucose and secrete lactate at a
higher rate than normal tissue, even under
aerobic conditions. - Known as the Warburg effect.
- Positron emission tomography (PET) - uses
a glucose analogue to detect a significant
increase in glucose uptake in tumours
Pyruvate oxidation - transition step
between Glycolysis & Kreb’s Cycle
- Moved to the
mitochondria - In the presence of O2
converted to 1
molecule of CO2 and
the remaining 2 C’s are
attached to Coenzyme
A, creating Acetyl CoA
using pyruvate
dehydrogenase
complex - Also generates a
molecule of NADH
Redox Reaction: NAD+ and NADH
Reduction (+ H+ and 2 e-)
Oxidation (- H+ and 2 e-)
Nicotinamide Adenine Dinucleotide: a coenzyme derived from vitamin B3 (Niacin)
TCA Cycle
TCA Cycle - 1. Citrate Synthase
* Citrate formed from acetyl CoA and
oxaloacetate
* Only cycle reaction with C-C bond formation
* Addition of C2 unit (acetyl) to the keto
double bond of C4 acid, oxaloacetate, to
produce C6 compound, citrate
TCA Cycle - 2. Aconitase
* Elimination of H2O from citrate to form
C=C bond of cis-aconitate
* Stereospecific addition of H2O to cis-
aconitate to form isocitrate
TCA Cycle - 3. Isocitrate Dehydrogenase
* Oxidative decarboxylation of isocitrate to alpha-ketoglutarate
* 1 of 4 oxidation-reduction reactions of the cycle
* Hydride ion from the C-2 of isocitrate is transferred to NAD+ to form NADH
* Oxalosuccinate is decarboxylated to a-ketoglutarate
isocitrate dehydrogenaseisocitrate dehydrogenase
TCA Cycle - 4. -Ketoglutarate Dehydrogenase Complex
* Similar to pyruvate dehydrogenase complex
* Same coenzymes, identical mechanisms
TCA Cycle - 5. Succinyl-CoA Synthetase
* Free energy in thioester bond of succinyl
CoA is conserved as GTP or ATP in higher
animals (or ATP in plants, some bacteria)
* Substrate level phosphorylation reaction
TCA Cycle - 6. Succinate Dehydrogenase Complex
* Complex of several polypeptides,
embedded in the inner mitochondrial
membrane
* Electrons are transferred from succinate
to FAD
TCA Cycle - 7. Fumarase
* Stereospecific trans addition of H2O to
the double bond of fumarate to form
L-malate
* Only the L isomer of malate is formed
TCA Cycle - 8. Malate Dehydrogenase
* Malate is oxidized to form oxaloacetate
Oxidative Phosphorylation
2 parts:
* Electron transport chain
* Chemiosmosis
Electron transport chain
- 4 complexes
- Electrons from NADH and
FADH2 - Protons pumped into
intermembrane space - Proton gradient formed
- Oxygen is reduced by the
electrons, forming water
Chemiosmosis
- H+ ions move
through ATP
synthase to
mitochondrial
matrix - ATP catalyses
the addition of
phosphate to
ADP→ATP
Summary
Perspective:
Adult human consumes
~40 kg/d of ATP
A resting-state human
brain utilizes ~5.7 kg
ATP/day, 5 times of the
brain weight.
A working muscle cell
makes and uses about
10 million molecules of
ATP every second
