Biochemistry and Biochemical Systems Modeling
4.3.2 r eView of c arBohydrate M etaBolisM
2 Cr2O72− + 28 H+ + 12 e−→ 4 Cr+++ + 14 H2O
(Electrons.are.gained.by.the.reduction.of.bichromate.). (4.40) To.summarize.organic.redox.reactions,.we.note.that.reducing agents remove.oxygen.from.another.
substance.or.give.hydrogen.to.it..A reducing agent is oxidized,.and.it.loses.electrons.(OIL)..Oxidizing agents.give.oxygen.to.another.substance.or.remove.hydrogen.from.it;.an oxidizing agent is reduced,.
and.it.gains.electrons.(RIG).
4.3.2 reView of carBohydrate MetaBolisM
You.have.already.been.introduced.to.one.aspect.of.carbohydrate (CHO).metabolism.in.the.sections.
on.glycolysis.and.the.citric.acid.cycle.earlier..In.this.section,.we.will.summarize.how dietary.CHOs.
reach.the.cells.and.how.liver.cells.store.glucose.in.the.form.of.the.polymer.glycogen and.then.release.
it.when.needed.
Cellulose.is.a.CHO.made.by.plant.cells;.it.is.a.linear.polymer.of.β-(1→ 4)-d-glucopryanose.units.
in.4C1.conformation..The.cellulose.polymer.consists.of.from.2,000.to.14,000.residues..It.forms.natural.
crystals.(cellulose.Iα.).in.which.intra-.and.intermolecular.hydrogen.bonds.make.it.mechanically.rigid.
and.insoluble.in.water.[Chaplin.2005]..Plants.use.this.ubiquitous.molecule.for.a.structural.material.
Humans.cannot.digest.cellulose..The.animals.that.do.(e.g.,.ruminants,.odd-.and.even-toed.ungu-lates,.beavers,.termites,.etc.).have.colonies.of.specialized.bacteria.in.their.digestive.systems.that.
break.cellulose.down.to.water-soluble.CHOs..Humans.obtain.dietary.CHOs.from.sugars.(mono-and.disaccharides),.starches.and,.of.course,.from.internally.stored.glycogen..The.sugars.include.
the.disaccharides.sucrose.(cane.sugar).and.lactose.and.the.monosaccharides.fructose.and.glucose..
Glucose.is.the.“entry.energy.molecule”.for.glycolysis,.thence.the.CA.cycle.
The first enzymatic step.in.the.digestion.of.CHOs.is.the.conversion.of.the.higher.polymers.to.
simpler,.soluble.forms.that.can.be.transported.across.the.walls.of.the.intestinal.epithelial.cells.and.
then.eventually.delivered.to.the.circulatory.system.for.distribution.to.body.cells..The.breakdown.
of.polymeric.CHOs.begins.in.the.mouth.with.the.enzyme.ptyalin (an α-amylase)..This.enzyme.
hydrolyzes.starch.into.the.disaccharide.maltose.and.other.small.polymers.of.glucose.containing.
three.to.nine.glucose.molecules,.such.as.maltotriose and.α limit dextrins.that.are.the.branch.points.
of.the.starch.polymer..About.3.to.5%.of.the.starches.eaten.are.hydrolyzed.in.the.mouth.before.being.
swallowed..However,.starch.digestion.continues.in.the.stomach,.although.the.salivary.α-amylase.
enzyme.is.eventually.inactivated.by.the.stomach.acid.having.a.pH.less.than.about.4..Perhaps.30.to.
40%.of.the.starches.in.the.stomach.are.broken.down.before.the.stomach.contents.(chyme).pass.into.
the.small.intestine.
There,.pancreatic.α-amylase completes.starch.hydrolysis.into.maltose.and.other.small.glucose.
polymers. before. the. chyme. has. passed. beyond. the. duodenum. or. upper. jejunum.. The. microvilli.
brush.border.of.the.epithelial.cells.lining.the.small.intestine.contains.the.enzymes.lactase, sucrase, maltase,.and.α-dextrinase whose.roles.are.to.split the.disaccharides.lactose, sucrose,.and.maltose.
as.well.as.other.small.glucose.polymers. Lactose.splits.into.a.molecule.of.galactose.and.a.molecule.
of.glucose..Sucrose.breaks.into.molecules.of.fructose.and.glucose..Maltose.splits.into.two.glucose.
molecules..The.resultant.monosaccharides.are.transported.across.the.epithelial.cell.walls.and.even-tually.turn.up.in.the.blood.of.the.hepatic portal vein.where.they.are.transported.to.the.liver.paren-chymal.cells.and,.later,.they.enter.the.metabolic.pathways.of.glycolysis,.the.citric.acid.cycle,.or.are.
converted.into.glycogen,.fatty.acids,.amino.acids,.etc..Glucose.and.triglycerides.are.distributed.to.
other.cells.in.the.body.by.the.circulatory.system..Figure.4.5.illustrates.the.steps.that.liver.cells.use.
to.synthesize.the.glucose.storage.polymer,.glycogen..Up.to.10%.of.liver.weight.can.be.glycogen.
Two. pancreatic. endocrine. hormones. control. the. synthesis. and. breakdown. of. liver. glycogen:.
insulin.and.glucagon..Insulin.is.secreted.by.the.pancreatic beta cells.in.response.to.rising.blood.
glucose.levels..It.activates.the.glucose.transmembrane.transport.proteins.in.insulin.sensitive.cells,.
letting. glucose. diffuse. into. these. cells. at. a. higher. rate.. It. also. activates. the. important. liver. cell.
enzyme.glucokinase.
Insulin.exerts.other.hormonal.effects.beside.its.major.one.of.facilitating.the.diffusion.of.extra-cellular.glucose.molecules.into.insulin-sensitive.cells..It.inhibits.gluconeogenesis;.it.does.this.by.
decreasing.the.quantities.and.activity.of.the.liver.enzymes.necessary.for.gluconeogenesis..It.also.
acts.to.decrease.the.rate.of.release.of.amino.acids.from.muscle.and.other.nonliver.tissues,.thus.
reducing.the.available.pool.of.precursor.molecules.used.in.gluconeogenesis,.and.promotes.the.con-version.of.excess.intracellular.glucose.into.fatty.acids..As.discussed.in.the.following.section,.the.
fatty.acids.are.converted.to.triglycerides.in.low-density.lipoproteins,.which.are.transported.to.adi-pose.tissues.where.they.are.made.into.fat. A.high.portal.insulin.concentration,.[I]p,.inhibits.the.
enzyme.glucose phosphatase in.liver.cells, an.enzyme.which.removes.the.phosphate.group.from.
glucose-6-phosphate. (G6P),. converting. it. to. glucose. that. can. diffuse. from. the. liver. back. to. the.
blood..High.[I]p.also.activates.the.liver.enzyme.phosphorylase. Phosphorylase.makes.G6P.from.
glucose.that.has.diffused.into.liver.cells,.thereby.trapping.the.glucose.inside.the.liver.cells..G6P.is.
enzymatically.converted.to.glucose-1-phosphate,.then.to.uridine diphosphate glucose, and.then.to.
the.glycogen polymer. Thus,.elevated.blood.insulin.concentration.increases.the.rate.at.which.liver.
glycogen.is.formed.and.also.inhibits.its.breakdown.
The.hormone.glucagon.is.made.by.the.pancreatic alpha.cells.of.the.islets.of.Langerhans..Its.
release.rate.is.stimulated.by.low.blood.glucose.concentration.([BG])..Normal.plasma.concentration.
of.glucagon.is.between.100.and.200.ng/L..One.of.the.major.effects.of.glucagon.is.to.raise.the.rate.
at.which.glycogen.is.broken.down,.releasing.glucose.stored.in.the.liver.cells.back.into.the.blood.
Introduction to Physical Biochemistry and Biochemical Systems Modeling
and.extracellular.fluid.(ECF)..Glucagon.also.stimulates.the.process.of.gluconeogenesis,.which.also.
raises.[BG].over.the.long.term..After.combining.with.glucagon.receptor.proteins.on.the.hepatic.
cell.membrane,.the.enzyme.adenyl cyclase.is.activated..Adenyl.cyclase.catalyzes.the.formation.
of.cyclic AMP.that.activates.the.following.series.of.reactions:.protein kinase regulator protein → protein kinase → phosphorylase b kinase → phosphorylase b → phosphorylase a..Phosphorylase.
a is.the.active.enzyme.that.cleaves.a.glycogen.unit,.forming.glucose-1-phosphate.(G1P)..G1P.is.
converted.to.G6P.by.another.enzyme,.and.then.phosphatase,.activated.by.glucagon,.removes.the.
phosphate.group.and.the.resulting.d-glucose.diffuses.out.of.the.liver.cell..Note.that.the.outward.
flow.of.glucose.occurs.during.periods.of.fasting.as.the.blood.glucose.regulator.attempts.to.main-tain.normoglycemia.
Gluconeogenesis is.activated.by.high.glucagon concentration.([GUN])..Several.metabolic.path-ways.are.involved,.and.many.enzymes.are.necessary.for.the.multistep.reactions..The.details.of.these.
glucose UDP-glucose synthase
OHO OHO OHO
OHO
OHO OHO
OH
Liver cell ..
.
1,6-bond A section of a T-branched
Glycogen polymer 1,4-bonds
. . . . . .
figuRe . Top: metabolic.pathways.in.liver.cells.in.which.the.polymer.glycogen.is.formed.and.broken.
down.and.released.into.the.portal.blood.as.d-glucose..Bottom:.2-D.structure.of.a.section.of.a.branched.glyco-gen.molecule,.showing.the.bonds.linking.the.sugars.