Marco Perikar R.

Dimaano 1BMed Class 2015

BIOCHEMISTRY OF CARBOHYDRATES
UST FMS
General Formula: C
x
(H
2
O)
y
or (CH
2
O)
n
Carbon compounds havi ng Carbonyl Carbon (C=O) and hydroxyl ( -OH) functi onal groups
Carbonyl Functional Groups:
Al dehyde (Pol yhydroxyal dehydes): 1
st
C (C=O)
Ketone (Pol yhydroxyketones): 2
nd
C (C=O)
Classification
1) Size of base Carbon chain
Tri ose (3C), Tetrose (4C), Pentose (5C), Hexose (6C), Heptose (7C), Nanose (9C)
2) Number of sugar units
Monosacchari de 1 CHO uni t
Di sacchari de 2 CHO uni ts
Ol i gosacchari de 3-10 CHO uni ts
Pol ysacchari de >10 uni ts
3) Location of Carbonyl carbon
Al dose
Ketose
Nomenclature

*Aldohexoses: ALL ALTruists GLadly MAke GUm IN GALlon TAnk.
2
nd
C: alternate OH
3
rd
C: alternate OH by 2
4
th
C: 1
st
4 Right OH, Last 4 Left OH
5
th
C: all OH at right side Ketoses

Ketotriose


Ketotetrose



Ketopentose




Ketohexose


Aldotriose
Aldotetrose
Aldopentose
Aldohexose
Marco Perikar R. Dimaano 1BMed Class 2015

Fischer Projection
Sugars drawn i n strai ght chai n
Perspective structural formula: 3D Fi sher
Haworth Projection
Cycl i c forms whi ch show the mol ecul es as cycl i c and
pl anar wi th substi tuents above or bel ow the ri ng
Boat and Chair conformation: more pl ausi ble bent forms
Fischer projection Haworth projection
Optical Activity
Abi l i ty to rotate pl ane of pol ari zed l i ght
Al l CHOs contai n assymetri cal (chi ral ) carbon and are, therefore,
optically active.
a. Dextrorotatory (+): D i somer
o Rotates to ri ght
o In Fi scher, -OH i s at the ri ght si de of penul ti mate Carbon
o In Haworth, l ast Carbon i s above the ri ng
b. Levorotatory (-): L i somer
o Rotate to l eft
o In Fi scher, -OH i s at the l eft si de of penul ti mate Carbon
o In Haworth, l ast Carbon i s bel ow the ri ng
*Assymetric or Chiral Carbon: carbon with 4 different substituents
*Penultimate Carbon: chiral carbon farthest from functional group

Stereochemistry
Isomers: same mol ecul ar formul a and bonds but di ffer i n spati al arrangement
A. Constitutional Isomers
Di fferent atom connecti vi ti es
B. Stereoisomers
Same atom connecti vi ty, di fferent spati al arrangement
2 types: Confi gurati onal and Conformati onal
1. Configurational Isomers
o Interconverted onl y by breaki ng coval ent bonds (separabl e)
o 4 types: Enanti omer, Di astereomer, Epi mer, Anomer
a. Enantiomer
Stereoi somers whi ch are non-superi mposabl e mi rror i mages of each
other (Eg. D-gl ucose and L-gl ucose)
b. Diastereomer
Stereoi somers whi ch are non-superi mposabl e non-mi rror i mages of
each other (Eg. D-gal actose and D-gl ucose)
c. Epimer
Stereoi somers whi ch di ffer i n one stereocenter (di fferent -OH
posi ti on al ong 1 Carbon atom onl y)
Exampl e: D-gl ucose, D-mannose and D-gal actose
d. Anomer
Stereoi somers whi ch di ffer onl y i n the confi gurati on around the
carbon (anomeri c carbon, usual l y C1) whi ch was i nvol ved i n the
i ntramol ecul ar nucl eophi l i c attack (Eg. and anomers)
Fischer Projection:
anomer (Cis): OH of anomeric Carbon and hemibridge on same side
anomer (Trans): OH of anomeric Carbon and hemibridge on opposite side
Haworth Projection:
anomer (Trans): C6 up, -OH of C1 (anomeric carbon) down if in D isomer
C6 down, -OH of C1 (anomeric carbon) up if in L isomer
anomer (Cis): C6 up, -OH of C1 (anomeric carbon) up if in D isomer
C6 down, -OH of C1 (anomeric carbon) down if in L isomer
*Mutarotation: and are in equilibrium
Marco Perikar R. Dimaano 1BMed Class 2015

2. Conformational Isomers
o Rel ated by rotati on around si ngl e bond (bendi ng
and twi sti ng)
o Interchange wi thout breaki ng coval ent bonds
o Boat and Chai r conformati on
a. Boat conformation: l ess stabl e due to steri c
hi ndrances
b. Chair conformation: more stabl e
*Axial Bond: perpendicular to plane
*Equatorial Bond: parallel to plane

Monosaccharides

Glucose
Central sugar i n metabol i sm
Can cycl i ze through i ntermol ecul ar nucl eophi l i c attack of one of
the OHs on the Carbonyl Carbon of the al dehyde
Occurs i f stabl e 5 or 6 member ri ngs can form
Furanose (5 member) or Pyranose (6 member)
On nucl eophi l i c attack to form the ri ng, carbonyl O becomes an OH
Fructose: 67% pyranose, 33% furanose
Ribose: 25%pyranose, 75% furanose
* Glucose is exclusively pyranose. Fructose and Ribose are exclusively furanose.

Monosaccharide Derivatives

1. Sugar Acids
Oxi di zed forms i n whi ch al dehyde and/or al cohol functi onal groups are oxi di zed to carboxyl i c aci d ( Oxi dati on)
a. Aldonic Acid
o Al dehyde group i s oxi di zed (Eg. Gl uconi c Aci d)
b. Uronic Acid
o Termi nal al cohol i s oxi di zed (Eg. Gl ucuroni c Aci d)
c. Aldaric Acid
o Both al dehyde and termi nal al cohol are oxi di zed
2. Sugar Alcohol
Reducti on of Carbonyl group to OH (-ol) (Eg. Dulcitol:
excess causes cataract in galactosemia patients)
3. Phosphorylated Sugar
Phosphate i s added by ATP formi ng phosphoester
deri vati ves
Eg. Gl ucose-6-Phosphate Glucose-6-Phosphate
4. Amino Sugars
Ami no group repl aced hydroxyl group (-OH to -NH)
Eg. Gl ucosami ne, Gal actosami ne
5. Acetylated Amine Derivative
Sugars deri ved from ami no sugars
Eg. N-acetyl gl ucosami ne, N-acteyl gal actosami ne
6. Lactone Forms
Intramol ecul ar esters
Hydroxyl group attacks Carbonyl carbon that was previ ousl y oxi di zed
to Carboxyl i c aci d (Eg. Gl uconol actone)
7. Deoxysugars
One or more Carbon atoms have been reduced, l osi ng hydroxyl
group (-OH to -H) (Eg. Deoxyri bose)


Marco Perikar R. Dimaano 1BMed Class 2015

8. Condensation Products of Sugar Derivatives with Lactate and Pyruvate
Forms Murami c Aci d (gl ucosami ne + l acti c aci d)
Forms Neurami ni c Aci d (mannosami ne + pyruvi c aci d)
N-acetyl murami c Aci d (MurNAc or NAM): Gl cNac + l acti c aci d (ether l i nk at C3)
o found i n bacteri al cel l wal l s
Sialic Acids:
o Found on surface of al l cel l s
o Invol ved i n cel l contact/communi cati on
o Invol ved i n recogni ti on bacteri a (chol era) and vi ruses (i nfl uenza)
o N-acetyl -neurami ni c Aci d (NANA):
N-acetyl mannosami ne (ManNac) + pyruvi c aci d
found onl y i n humans
l ack hydrol ase gene (92 base pai rs of gene mi ssi ng)
o N-gl ycoyl -neurami ni c Aci d: N-gl ycoyl mannosami ne + pyruvi c aci d
Have hydroxyl ase








Neuraminic Acid

Oligosaccharides











Polysaccharides

Homopolysaccharides: pol ysacchari des wi th 1 type of repeati ng monosacchari de uni t
Starch: found i n pl ants; composed of:
o Amylose (20%)
Li near chai n of Glc i n 1-4 l i nks (or repeati ng mal toses)
o Amylopectin (80%)
Branched chai n i n 1-6 l i nks
o Major part: Glc chai n of 24-30 uni ts (amyl ose) then branches
off (amyl opecti n)
Glycogen
o Mai n carbohydrate storage i n ani mal s
o Composed of Glc resi dues i n 1-4 l i nks and 1-6 branches
(greater than starch)
o Synthesi zed on Glycogenin protei n pri mer
o Reason why gl ycogen i s stored rather than gl ucose: Has l ess osmoti c pressure than gl ucose, therefore, does not easi l y
reacts wi th water
o Source: Muscl es (greatest source i n terms of total gl ycogen mass source) and l i ver (greatest source i n terms of grams
gl ycogen per gram ti ssue)
Marco Perikar R. Dimaano 1BMed Class 2015

Cellulose
o Li near chai n of Glc resi dues i n 1-4 l i nks (or repeati ng cel l obi ose)
o Hel d together by i ntra- and i nter-chai n H-bonds
o Most abundant bi ol ogi cal mol ecul e i n nature; cannot be broken
down by humans (l ack of cel l ul ase)
Chitin
o Li near chai n of GlcNAc i n 1-4 l i nks
Heteropolysaccharides: pol ysacchari des wi th 2 di fferent monosacchari de uni ts
Complex Oligosaccharide Units
Mucopolysaccharides/Glycosaminoglycans (MPS/GAG)
o Ami no sugar + negati vel y charged sul fate or
carboxyl group (uroni c aci d: gl ucuroni c or i duroni c
aci d)
o Form matri x to hol d protei n component of ski n,
connecti ve ti ssue and extracel l ul ar matri x
o Often coval entl y attached to protei ns to form
proteogl ycans
o Hyaluronic Acid Hyaluronic Acid Dermatan Sulfate
Gl ucuronate(1-3)Gl cNAc
Water sol ubl e; found i n synovi al fl ui d
Backbone for attachment protei ns
o Dermatan Sulfate
L-Iduronate(1-3)Gal NAc-4-Sul fate
o Chondroitin Sulfate
D-Gl ucoronate(1-4)Gal NAc-4or6-Sul fate
o Heparin
D-Gl ucoronate-2-Sul fate(1-4)Gl cNSul fo-6-Sul fate Chondroitin Sulfate Heparin
Anti thrombi n, natural l y-occurri ng anti coagul ant
o Keratan Sulfate
D-Gal (1-4)Gl cNAc-6-Sul fate
No uroni c aci d component
o Syndecan Heparan Sulfate
Bi nds through i ntracel l ul ar domai n to the cytoskel eton
Interacts wi th fi bronecti n
o Glypican Heparin Keratan Sul fate
Attached to outer surface of pl asma membrane vi a
phosphati dyl i nositol l i pi d
Peptidoglycans
o Bacterial Cell Walls
Offer protecti on from hypotoni c condi ti on and hi gh i nternal osmoti c
pressure
Long chai n of GlcNAc(1-4)MurNAc (NAG,NAM)
Gram (+) Bacteria
Mul ti -l ayered; cel l wal l can be Gram stai ned (vi ol et)
Chai ns are coval entl y connected by a Pentaglycine Bridge through the
-Ami no group of tetrapepti de Lysi ne on one
strand and D-Al ani ne on another strand
Teichoic Acid
Al ternati ng resi due of D-Al a and NAG i n C2 Gl ycerol
or Ri bi tol Phosphate backbone
Mul ti pl e gl ycerol s are l i nked through Phosphodi ester
Bonds
Often attached to C6 of NAM
Make up 50% of cel l wal l dry wei ght
Present a forei gn anti geni c surface to i nfected host
Serve as receptors for bacteri ophages
Marco Perikar R. Dimaano 1BMed Class 2015

Gram (-) Bacteria
Cel l wal l cannot be Gram-stai ned (red)
No pentagl yci ne bri dge; chai ns are connected by di rect ami de bond between the -Ami no group of
tetrapepti de Lysi ne on one strand and D-Al ani ne on another strand
Hydrophobi c protei n coval entl y attaches (through Lys ami de bond) to the l ast ami no aci d i n the tetrapepti de
uni t of cel l wal l (actual l y di ami nopi mel i c aci d/DAP, whi ch repl aces 10% of D-Al a i n cel l wal l )
No tei choi c aci d; Cel l wal l sandwi ched between l i pi d bi l ayer; Peri pl asmi c space space between l i pi d bi l ayers
Lipopolysaccharide (O anti gen) coats the outer membrane and determi nes anti geni ci ty of bacteri a
Proteoglycans
o GAG coval entl y O-l i nked to protei n (usual l y to Ser resi due
of Ser-Gl y di pepti des)
o May contai n N-l i nked ol i gosacchari de groups
o Carbohydrates > Protei ns
o Sol ubl e
o CHO part provi des an i ncredi bl e vari ety of bi ndi ng
structures (acts l i nke gl ue) i n connecti ng i ntra- and
extracel l ul ar cel l functi ons
o Syndecan: protei n + hepari n sul fate + chondroi ti n sul fate;
bi nds through i ts i ntracel l ul ar domai n to the i nternal
cytoskel eton of the cel l whi l e i nteracti ng wi th fi bronecti n
i n the extracel l ul ar matri x
o Aggrecan: protei n + Chondroi ti n sul fate + Keratan sul fate; bi nds hyal uroni c aci d; i mportant i n hydrati on of carti l ages
o Versican: protei n + Chondroi ti n sul fate; bi nds hyal uroni c aci d i n extracel l ul ar matri x
Glycoproteins/Glycosylated Proteins
o Protei ns post-transl ati onal l y modi fi ed by attachment of carbohydrates
o Usual l y attached through ei ther Asn or Ser si de chai ns
o Invol ved i n recogni ti on of bi ndi ng mol ecul es, preventi on of aggregati on
duri ng protei n fol di ng, protecti on from preoteol ysi s , i ncrease i n protei n
hal f-l i fe, bl ood cl otti ng, i mmunol ogi c protecti on and ABO bl ood groups.
o N-linked glycoproteins
Carbohydrate attached to ei ther Gl cNAc or Gal NAc to an Asn i n a X-
Asn-X-Thr sequence of protei n
Core ol i gosacchari de: (Man)
3
(GlcNAc)
2
attached to Asn
3 types: Mannose, Compl ex, Hybri d
o O-linked glycoproteins
Carbohydrate usual l y attached from a Gal (1-3)Gal NAc to a Ser or
Thr of a protei n
Eg. Bl ood Group Anti gens
Storage Polysaccharides: Starch, Gl ycogen
Structural Polysaccharides: Cel l ul ose, Chi ti n, GAGs, Pepti dogl ycans
Marco Perikar R. Dimaano 1BMed Class 2015

Hemiacetal and Hemiketal Formation

Al dehyde or ketone group of monosacchari des can cycl ize through i ntramol ecul ar nucl eophi l i c attack of a hydroxyl group ( -OH)
at the Carbonyl carbon i n an addi ti on reacti on formi ng Hemi acetal or Hemi ketal , respecti vel y.
On addi ti on of aci d: anomeri c OH i s protonated, formi ng water, a l eavi ng group
Another al cohol can be added formi ng Acetal or Ketal

Reducing Property of Sugars

Reducing Sugars: sugars whi ch can form an al dehyde at C1 or have an -hydroxymethyl ketone group whi ch can i someri ze
to an al dehyde under basi c condi ti ons, such as fructose
o Eg. Al l common monosacchari des, mal tose
o Eg. Lactose: Si nce Gl c i s attached through the OH on C4, i ts anomeri c carbon coul d revert to noncycl i c al dehyde form,
whi ch i s suscepti bl e to oxi dati on , thus, subsequentl y reduced.
Non-Reducing Sugar: sugars i n whi ch there are no al dehyde or ketone group to react; sugar ri ngs are l ocked or not capabl e
of openi ng
o Eg. Sucrose: Si nce the anomeri c carbons of both Gl c and Fru are l i nked, i t cannot be reduced (nei ther of the ri ngs can
be opened).
Tests for i denti fyi ng Reduci ng Sugars:
o Benedicts: Copper Sul fate + Al kal i ne Ci trate; deep bl ue bri ck red ppt
o Fehlings: Copper Sul fate + Al kal i ne Tartrate; deep bl ue bri ck red ppt
o Tollens: Si l ver Ni trate + Aqueous Ammoni a; col orl ess si l ver mi rror