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METABOLISM OF CARBOHYDRATES
DIGESTION The digestion of carbohydrates in the diet starts in the mouth. The enzyme,
salivary amylase ptyalin acts on starch and glycogen producing limited quantities of maltose.
As the partially digested carbohydrates goes into the stomach, digestion stops as there are
no enzymes capable of digesting carbohydrates in the stomach. Final digestion of
carbohydrates occurs in the small intestine through the action of pancreatic juice, which
contains the enzymes pancreatic amylase converts partially degraded polysaccharides to
maltose with the help of splitting enzyme, maltase converts maltose to glucose, sucrase
converts sucrose to glucose and fructose and lactase converts lactose to glucose and
galactose. Ingested carbohydrates are thus converted into glucose, fructose, galactose
together with smaller quantities of mannose and pentoses. ABSORPTION The
monosaccharides produced during digestion are transported across the small intestine. The
sugars absorbed travel via the portal vein to the liver and are stored as glycogen.
GLYCOGEN SYNTHESIS Since glycogen consists of glucose residues only, the other
hexoses are first converted to glucose or derivatives prior to incorporation into glycogen.
Glucose is first converted to glucosephosphate by the enzyme hexokinase and ATP.
Glucosephosphate is then converted to glucosephosphate by the action of
phosphoglucomutase in the presence of glucose,diphosphate. Fructose is converted to
fructosephosphate by the action of hexokinase and ATP. The action of
phosphohexoisomerase converts fructosephosphate to glucosephosphate, which can be
converted into glucosephosphate. Galactose is converted to galactosephosphate by the
action of galactokinase and ATP. Galactosephosphate is converted to glucosephosphate by
galactosephosphate uridyl transferase in the presence of UDPglucose producing in the
process UDPgalactose, which is then converted into UDPglucose by uridine
diphosphoglycosylepimerase. Mannose is converted to mannosephosphate by the action of
hexokinase and ATP. Mannosephosphate is converted to fructosephosphate by
phosphomannose isomerase. The action of phosphoglucoisomerase converts
fructosephosphate to glucosephosphate, which is then converted to glucosephosphate by
phosphoglucomutase.
Glucosephosphate reacts with UTP to produce UDPglucose by the action of the enzyme
UDPglucose pyrophosphorylase. The initiation of glycogen synthesis requires a primer. The
hydroxyl group of a specific tyrosine of the protein glycogenin serves as the primer, a
glucose residue is linked to the tyrosine hydroxyl in the first stage of glycogen synthesis. The
addition of UDPglucose to a growing chain of glycogen is the next step in glycogen
synthesis. Each step involves the formation of glycosidic bond in a reaction catalyzed by the
enzyme glycogen synthase. UDP is release in the process and it reacts with ATP to produce
UTP, which combines with another glucosephosphate. The formation of glycosidic linkages is
accomplished by a branching enzyme, which transfers a segment about seven residues in
length from the end of a growing chain to a branch point and catalyzes the formation of
glycosidic linkage. GLUCOSE METABOLISM GLYCOLYSIS Glucose metabolism is primarily
for the production of energy in the form of ATP needed for all cellular processes. The first
stage of glucose metabolism, glycolysis, is an anaerobic process which yields two molecules
of ATP. The glycolytic pathway, also called the EmbdenMeyerhoff pathway involves many
steps.
. Fructose phosphate is further phosphorylated producing fructose.Steps in the Glycolytic
Pathway . This is another energy requiring reaction. Glucosephosphate isomerizes to give
fructosephosphate by the action of the enzyme glucosephosphate isomerase.bisphosphate
by the action of the enzyme phosphofructokinase in the presence of Mg. Glucose is
phosphorylated to give glucosephosphate by the enzyme hexokinase in the presence of Mg.
. This is an energy requiring step and the energy required is provided by ATP. the energy is
again provided by ATP. .
. . Oxidation of glyceraldehydephosphate to . Conversion of phosphoglycerate to
phosphoglycerate by the enzyme phosphoglyceromutase in the presence of Mg. .
phosphoglycerate undergoes a dehydration reaction into phosphoenolpyruvate by the action
of the enzyme enolase in the presence of Mg. . . Fructose. This reaction involves oxidation of
glyceraldehydephosphate resulting to electron transfer from glyceraldehydephosphate to
NAD and the addition of a phosphate group to glyceraldehydephosphate substrate level
phosphorylation.bisphosphoglycerate is converted to phosphoglycerate by the enzyme
phosphoglycerate kinase. Dihydroxyaceone phosphate is converted by the action of
triosephosphate isomerase to glyceraldehydephosphate. . dihydroxyacetone phosphate and
Dglyceraldehydephosphate.bisphosphoglycerate by the action of the enzyme
glyceraldehydephosphate dehydrogenase. . by the enzyme aldolase.. This reaction involves
substrate level phosphorylation of ADP producing ATP.bisphosphate is split into carbon
fragments.
. also known as Krebs Cycle and Tricarboxylic Acid Cycle. Conversion of pyruvate to ethanol
alcoholic fermentation via a twostep reaction a. . Conversion of pyruvate to acetaldehyde by
pyruvate decarboxylase. O alcohol dehydrogenase HCCH CHCHOH NAD CITRIC ACID
CYCLE The Citric Acid Cycle. b.bisposphoglycerate step ATP are produced in the
conversion of phosphoenolpyruvate step Net ATP produced in glycolysis ATP ATP ATP ATP
Anaerobic Reactions of Pyruvate . . This reaction regenerates the NAD used in Step of
glycolysis. Energy Considerations in Glycolysis ATP are used up in the conversion of
glucose to pyruvate step and step ATP are produced in the conversion of . This reaction
regenerates NAD. Transfer of phosphate group from phosphoenolpyruvate to ADP producing
ATP and pyruvate by the action of pyruvate kinase and Mg. involves the oxidation of
pyruvate produced in glycolysis under aerobic conditions with carbon dioxide and water as
the final products. Conversion of pyruvate to lactate in the muscle by the action of lactate
dehydrogenase. Conversion of acetaldehyde to ethanol by alcohol dehydrogenase.
. AcetylCoA condenses with oxaloacetate to form citrate and CoA by the action of citrate
synthase. which becomes linked to an intermediate. Coenzyme A CoA. The enzyme
aconitase converts citrate an achiral compound to isocitrate a chiral compound. In this
reaction. NAD accepts electrons and become reduced to NADH. Isomerization of Citrate to
Isocitrate. Pyruvate is first oxidatively decarboxylated to one CO and one acetyl group. The
enzyme responsible for this conversion is pyruvate dehydrogenase complex. The acetylCoA
enters the Citric Acid Cycle and the following reactions take place . Formation of Citrate.
Many cofactors are also needed as shown in the reaction below. . which is composed of
many enzymes.
Succinate is oxidized to fumarate by the action of the enzyme succinate dehydrogenase.
Ketoglutarate is oxidatively decarboxylated and forms succinylCoA with CoA in a reaction
that occurs in several stages and catalyzed by the enzyme system. only Lmalate is
produced. Formation of Ketoglutarate and CO. FAD. . An electron acceptor. but of the two
enantiomers of malate. .. Formation of LMalate. Isocitrate is oxidatively decarboxylated to
Ketoglutarate and CO by the action of the enzyme isocitrate dehydrogenase. . Formation of
Fumarate. a molecule of GTP is synthesized from GDP. which accepts two electrons and
become reduced to NADH. becomes reduced to FADH. Formation of Succinate. This
reaction involves NAD. . NAD is the electron acceptor and consequently is reduced to NADH.
. . The thioester bond of succinylCoA is hydrolyzed to produce succinate and CoASH by the
action of succinylCoA synthetase. Formation of SuccinylCoA and CO. Regeneration of
Oxaloacetate. ketoglutarate dehydrogenase complex. In the reaction. Lmalate is oxidized to
oxaloacetate by the action of the enzyme malate dehydrogenase. Fumarate is hydrated
producing malate by the action of fumarase.
Energy considerations in the Citric Acid Cycle Oxidative decarboxylation of pyruvate
produces NADH ATP Conversion of isocitrate to oxalosuccinate produces NADH ATP
Conversion of ketoglutarate to succinylCoA produces NADH ATP Conversion of succinylCoA
to succinate produces GTP ATP Conversion of succinate to fumarate produces FADH ATP
Conversion of malate to oxaloacetate produces NADH ATP Total ATP production per
pyruvate ATP Total ATP production per glucose since pyruvate are produced ATP The
production of ATP from GTP is easily determined. In the process NADH and FADH are
oxidized back to NAD and FAD and these can be used again in various metabolic pathways.
Electron Transport Chain . thus. is reduced to water. the Electron Transport Chain completes
the process by which glucose is completely oxidized to carbon dioxide and water.
ELECTRON TRANSPORT AND OXIDATIVE PHOSPHORYLATION The Citric Acid Cycle
undergoes under aerobic conditions. but the reactions in the Electron Transport Chain are
strongly linked to one another and are tightly coupled to synthesis of ATP by phosphorylation
of ADP. Oxygen. Production of ATP in the cell requires the process of oxidative
phosphorylation. The reactions in the Electron Transport Chain take place in the inner
mitochondrial membrane. since the Citric Acid Cycle is linked to the Electron Transport
Chain. The Electron Transport Chain is a series of reactions in which NADH and FADH
generated in Glycolysis and Citric Acid Cycle. in which ADP is phosphorylated to give ATP.
transfer electrons to oxygen. since GTP can transfer its Pi to ADP GTP ADP ATP GDP ATP
are generated from NADH and FADH in the Electron Transport System. there is no reaction
in the cycle itself that involves oxygen. the ultimate electron acceptor. The production of ATP
by oxidative phosphorylation is a process separate from electron transport. however. The
energy released by oxidation of nutrients is used by organisms in the form of chemical
energy of ATP. This is so.
succinateCoQ Oxidoreductase. The overall reaction is Succinate CoQ fumarate CoQH.
NADHCoQ Oxidoreductase. This reaction has no enough energy to drive the
phosphorylation of ADP to ATP. EFADH CoQ EFAD CoQH. The reduced flavoprotein is
reoxidized and CoQ is reduced to CoQH by accepting the electrons from the flavoprotein via
the ironsulfur clusters. thus the Q cycle. Complex III. The reaction catalyzed by the complex
provides enough energy to drive the phosphorylation of ADP to ATP. EFMNH FeSox EFMN
FeSred H FeSred CoQ H FeSox CoQH The overall reaction is NADH H CoQ NAD CoQH.
However its source of electrons differs from Complex I because its substrate is succinate in
the Citric Acid Cycle. . This complex. catalyzes the first steps of electron transport. This
reaction releases enough energy to drive the phosphorylation of ADP to ATP. which are
multienzyme systems Complex I. Complex II This complex. catalyzes the transfer of
electrons to CoQ. which is oxidized to fumarate by a flavin enzyme. catalyzes the oxidation
of CoQH. namely the transfer of electrons from NADH to coenzyme Q CoQ.The Electron
Transport Chain consists of four separate respiratory complexes. rather a cyclic flow of
electrons involves CoQ twice. The overall reaction is CoQH cyt cFeIII CoQ cyt cFeII H The
flow of electrons from CoQH to the other components of the complex does not take a simple
direct path. CoQHcytochrome c oxidoreductase also called cytochrome reductase. The
reaction occurs in several steps Transfer of electrons from NADH to the flavin portion of the
flavoprotein EFMN NADH H EFMN NAD EFMNH. This complex. The electrons produced by
this oxidation reaction are passed along to cytochrome c in a multistep process. Succinate
EFAD fumarate EFADH The flavin group is reoxidized in the next stage of the reaction and
CoQ is reduced to CoQH.
However. cytochrome oxidase. which is then reduced to FADH and FADH passes the
electrons through the electron transport chain. In the process the electrons are passed to
FAD. the copper ions are intermediate electron acceptors that lie between the two atype
cytochromes in the sequence Cyt c cyt a Cu cyt a O This reaction provides enough energy
for the phosphorylation of ADP to ATP. The glycerol phosphate crosses the mitochondrial
membrane and inside the mitochondrion. The overall reaction is cyt cFeII H O cyt cFeIII HO
In the flow of electrons. catalyzes the final steps of electron transport. This shuttle makes use
of the fact that glycerol phosphate can cross the mitochondrial membrane. . the transfer of
electrons from cytochrome c to oxygen. SHUTTLE SYSTEMS BETWEEN MITOCHONDRIA
AND CYTOSOL Glycolysis occurs in the cytosol and NADH produced by glycolysis cannot
cross the mitochondrial membrane to enter the Electron Transport Chain. which oxidizes
NADH to NAD. there are carriers that can accept the electrons from NADH and can cross the
mitochondrial membrane. Glycerol Phosphate Shuttle This shuttle has been observed in
mammalian muscle and brain.Complex IV This complex. which can cross the mitochondrial
membrane. leading to the production of two molecules of ATP per molecule of NADH in the
cytosol. The glycerol phosphate is produced by the reduction of dihydroxyacetone
phosphate. is reoxidized back to dihydroxyacetone phosphate.
liver and heart.MalateAspartate Shuttle This shuttle has been observed in mammalian
kidney. which crosses the mitochondrial membrane. the electrons are transferred to NAD. .
In the cytosol. Malate crosses the mitochondrial membrane and in the mitochondrion.
accompanied by the oxidation of cytosolic NADH to NAD. In the process. In the cytosol.
oxaloacetate is reduced to malate by the cytosolic malate dehydrogenase. aspartate is
converted to oxaloacetate. This shuttle makes use of the fact that malate can cross the
mitochondrial membrane but oxaloacetate cannot do so. The NADH passes the electrons to
the electron transport chain leading to the production of ATP per molecule of cytosolic
NADH. Oxaloacetate is converted to aspartate. which is reduced to NADH. malate is
converted back to oxaloacetate by mitochondrial malate dehydrogenase.
bisphosphate .bisphosphoglycerate phosphoglycerate Phosphoenolpyruvate pyruvate
Oxidation of glyceraldehydephosphate Mitochondrial Reactions Pyruvate AcetylCoA Citric
Acid Cycle GDP GTP Oxidation of succinate Oxidation of isocitrate Oxidation of ketoglutarate
Oxidation of malate Oxidative Phosphorylation Electron Transport Reoxidation of NADH
produced in glycolysis Reoxidation of NADH from pyruvateacetylCoA Reoxidation of FADH
produced in CAC Reoxidation of NADH produced in CAC TOTAL PER MOLECULE OF
GLUCOSE Using glycerol phosphate shuttle mammalian muscle and brain Using
malateaspartate shuttle mammalian kidney. liver and heart FADH ATP YIELD .ATP YIELD
FROM COMPLETE OXIDATION OF GLUCOSE REACTIONS NADH Cytoplasmic Reactions
Glycolysis Glucose Glucosephosphate Fructosephosphate fructose .
The absorbed amino acids are absorbed into the blood and transported to the liver.
Glutamate is the major donor of amino groups in amino acid biosynthesis and ketoglutarate
is the major acceptor of amino groups. In the stomach proteins are converted into shorter
peptide fragments but few free amino acids. Amino Acid Biosynthesis The biosynthesis of
amino acids involves a common set of reactions transamination transfer of amino groups.
Lamino acids are absorbed more rapidly than Damino acids. The gastric juice of young
animals also contains rennin. Chymotrypsin hydrolyzes peptide bonds containing carboxyl
groups of aromatic amino acids. Absorption Absorption of amino acids takes place by a
process of selective transport. Trypsinogen is converted into active trypsin by the enzyme
enterokinase. The major proteolytic enzyme in the stomach is pepsin. while
carboxypeptidase B cleaves Cterminal arginine or lysine residues. and proelastase. Pepsin
preferentially attacks peptide bonds involving residues of aromatic amino acids. which is
secreted by the chief cells of the gastric mucosa as pepsinogen and consequently converted
to pepsin by pepsin itself at the acid pH of the gastric juice. a milkclotting enzyme. including
their degradation takes place. . such as formyl or methyl groups. Chymotrypsinogen is
converted into active chymotrypsin by the action of free trypsin and chymotrypsin.PROTEIN
METABOLISM Digestion The digestion of proteins starts in the stomach. The remaining short
peptides are then degraded completely to yield free amino acids by peptidases found in and
secreted by the intestinal mucosa. The next stage of protein digestion occurs in the small
intestine. Carboxypeptidase A hydrolyzes nearly all Cterminal peptide bonds. The pancreatic
juice secreted into the small intestine contributes the zymogens chymotrypsinogen. and
transfer of onecarbon units. Glutamate is formed from NH and ketoglutarate in a reductive
amination that requires NADPH catalyzed by glutamate dehydrogenase. Trypsin hydrolyzes
peptide linkages involving arginine and lysine. where much of the further metabolism of
amino acids. procarboxypeptidases A and B. methionine and leucine. The amino acids
undergoing similar pathways may be grouped into families. trypsinogen. Proteins are
converted into short peptides and free amino acids. The conversion of glutamate to
glutamine is catalyzed by glutamine synthetase in a reaction that requires ATP.
The hydroxyl group on carbon is oxidized to a keto group. Pyridoxal phosphate forms a
Schiff base with the amino group of substrate I the amino acid donor. Enzymes that catalyze
transamination reactions require pyridoxal phosphate as coenzyme. A transamination
reaction in which glutamate is the nitrogen donor produces phosphoserine. . which is
obtainable from the glycolytic pathway. Substrate II another keto acid then forms a Schiff
base with pyridoxamine. The next stage is a rearrangement followed by hydrolysis. Again
there is a rearrangement followed by hydrolysis. which removes product I the keto acid
corresponding to substrate I. The coenzyme now carries the amino group pyridoxamine.
which gives rise to product II an amino acid and regenerates pyridoxal phosphate. The
ultimate precursor of serine is phosphoglycerate. A good example of a onecarbon transfer
reaction can be found in the reactions that produce the amino acids of the serine family.
Hydrolysis of the phosphate group then gives serine. giving an keto acid. The net reaction is
that an amino acid substrate I reacts with an keto acid substrate II to form an keto acid
product I and an amino acid product II.
Excess nitrogen is excreted in one of three forms ammonia as ammonium ion. a condition
characterized by the breakdown of the bodys own proteins. Glucogenic amino acids can be
converted to glucose. In catabolism. Some organisms can synthesize all amino acids that
they need. This is illustrated in the diagram. Isoleucine. that live in aquatic environment
excrete nitrogen as ammonia. they are protected from the toxic effects of high concentrations
of ammonia not only by the removal of ammonia from their bodies but also by rapid dilution
of the excreted ammonia by the water in the environment. but ketogenic amino acids cannot.
Valine. leaving behind the carbon skeleton. The amino acids degraded to acetylCoA and
acetoacetylCoA are used in the citric acid cycle. . and Tryptophan. The nitrogen portion of
amino acids is involved in transamination reactions in breakdown as well as in biosynthesis.
Histidine. Animals. The principal waste product of nitrogen metabolism in terrestrial animals
is urea. These amino acids are considered essential amino acids and are coded
PHILTVMALT. A ketogenic amino acid is one that breaks down to acetylCoA or
acetoacetylCoA. urea and uric acid. including humans. with oxaloacetate as an intermediate.
Breakdown of the carbon skeleton of amino acids follows two general pathways. Catabolic
breakdown of amino acids produces citric acid cycle intermediates while anabolic formation
of amino acids uses citric acid cycle intermediates as precursors. a waterinsoluble
compound. must obtain some amino acids from dietary sources. Methionine. Catabolism of
Amino Acids The Urea Cycle The first step to consider in the catabolism of amino acids is the
removal of nitrogen by transamination. such as fish. and they do not have to carry excess
weight of water. A glucogenic amino acid is one that yields pyruvate or oxaloacetate on
degradation. Threonine. especially in the case of growing children. the amino nitrogen of the
original amino acid is transferred to ketoglutarate to produce glutamate. This fact is the
source of distinction between glucogenic and ketogenic amino acids. leading to the formation
of ketone bodies. but mammals cannot synthesize glucose from acetylCoA. Oxaloacetate is
the starting point for the production of glucose by gluconeogenesis. depending on the type of
endproduct. Insufficient supply of essential amino acids leads to the disease kwashiorkor.
Birds excrete nitrogen in the form of uric acid. While transamination occurs in anabolism of
amino acids. the anabolic and catabolic pathways are not exactly the reverse of each other.
Lysine. which could hamper flight. a watersoluble compound. which stands for
Phenylalanine. Leucine. The body can synthesize some of these amino acids but not in
sufficient quantities for its needs. Arginine. Other species. to rid themselves of waste
products.
Arginosuccinate is split to produce arginine and fumarate. Summary of Catabolic and
Anabolic Processes Summary of Catabolism Summary of Anabolism . A condensation
reaction between the ammonium ion and carbon dioxide produces carbamoyl phosphate in a
reaction that requires two molecules of ATP for each molecule of carbamoyl phosphate.
Finally. The immediate precursor is glutamate. but the ammonia nitrogens of glutamate have
ultimately come from many sources as a result of transamination reactions. arginine is
hydrolyzed to give urea and to regenerate ornithine. Carbamoyl phosphate reacts with
ornithine to form citrulline. A second nitrogen enters the urea cycle when aspartate reacts
with citrulline to form arginosuccinate in another reaction that requires ATP. The nitrogens
that enter the urea cycle do so first as ammonia in the form of ammonium ion. The
elimination of nitrogen as urea constitutes the urea cycle. The amino group of the aspartate
is the source of the second nitrogen in the urea that will be formed in this series of reactions.