Chapter 11 - Carbohydrates and Glycoproteins

carbohydrate

carbon based molecule high in hydroxyl groups. also known as polyhydroxyl aldehydes or ketones

carbohydrate empirical formula

(CH2O)n

monosaccharides

"simple sugar" aldehydes or ketones that contain two or more hydroxyl groups

3-7 carbons in length

have many isomers

monosaccharide nomenclature

chain length (3 C chain = trioses, 7 C chain = heptoses)

most oxidized group (if it's the keto group = molecule is a ketose)

constitutional isomers

molecules with identical molecular formulas that differ in how the atoms are ordered

stereoisomers

molecules that differ in spatial arragement but not bonding order

- L or D

- enantiomers or diastereoisomers

determining the number of possible stereoisomers

2^n where n is the number of asymmetric carbon atoms

enantiomers

mirror images of each other

diastereoisomers

not mirror images of each other

epimers

sugars that are diastereoisomers differing in configuration only at a single asymmetric center

monosaccharides in vivo

exist as interchanging cyclic forms, mostly found in cyclic forms

aldehyde + alcohol = hemiacetal

ketone + alcohol = hemiketal

pyranose formation

when a glucose-based molecule in strand formation folds into a ring formation resembling pyran (6 carbon ring)

furanose formation

when a glucose-based molecule in strand formation folds into a ring formation resembling furan (5 carbon ring)

anomer

diastereoisomeric form of sugars that forms when a cyclic hemiacetal is formed and an additional asymmetric center is created upon ring closure

D-fructose anomers

C2 is the anomeric carbon

pyranose form (2 anomers) most abundant in solution

furanose form (2 anomers) most abundant in fructose derivatives

pyranose ring conformation

chair and boat confirmations

chair confirmations

substituents are either axial or equitorial. axial subs will hinder each other if on the same side of the ring

conformations of B-D-Glucose

a pyranose molecule. chair is most abundant bc hydrogens take the axial positions and boat is very sterically hindered

what is blood sugar

the D-glucose that circulates in the blood

- only fuel used by brain and RBCs in non-starving conditions

why is D-glucose an important fuel

- glucose can be formed from formaldehyde under prebiotic conditions, suggesting availability as food source for primitive biochemical systems

- glucose is relatively inert

- most stable structure is B-D-glucopyranose

glycation

nonenzymatic addition of a carbohydrate to another molecule

example of glycation

reducing sugars will nonspecifically react with free amino groups on proteins (Lys or Arg) to form a stable covalent bond

D-glucose glycation

D-glucose has a low tendency to glycate proteins unless concentrations of sugar and protein are very high for long periods of time

advanced glycation end products (AGEs)

products resulting from cross-linking following the primary modifications

implicated in aging, arteriosclerosis, diabetes, and other pathological conditions

A1C levels

D-glucose reacts with hemoglobin to form glycated hemoglobin, which is what A1C's track. eliminated when RBCs die (120 days)

<6% glycated hemoglobin = nondiabetic

~10% glycated hemoglobin = uncontrolled diabetes

modifications to monosaccharides

increase biochemical versatility by allowing monosaccharides to act as signal molecules or facilitate metabolism

need to be reacted with an alcohol, amine, or phosphate

O-glycosidic linkage

covalent linkage formed between the anomeric carbon atom of a carbohydrate and the oxygen atom of an alcohol

N-glycosidic linkage

covalent linkage formed between the anomeric carbon atom of a carbohydrate and the nitrogen atom of an amine

phosphyrylation

a common modification of sugars in metabolism reactions, phosphorylates sugars can be seen as intermediates

purpose of phosphorylating sugars

- make them anionic to prevent crossing the cell membrane and interacting with other transport proteins

- blocks the formation of alternative ring conformation

- creates reaction intermediates that more readily undergo metabolism

oligosaccharides

sugars that contain 2 or more monosaccharides linked by O-glycosidic bonds

oligosaccharide directionality

defined by their reducing and nonreducing ends

reducing end

has a free anomeric carbon atom that can form the open-chain form

nonreducing end

has an anomeric carbon in a glycosidic linkage that cannot convert to the open-chain form

a-1,4-glycosidic linkage

glycosidic linkage between the a-anomeric form of C-1 on one sugar and the hydroxyl oxygen atom on the C-4 of the adjacent sugar

disaccharide

two sugars joined by an O-glycosidic linkage

role of disaccharides

cleavage products can be processed to provide ATP energy

common disaccharides

sucrose, lactose, maltose

sucrose

disaccharide of sugar cane or sugar beets consisting of glucose linked to fructose at anomeric carbons

- alpha glucose and beta fructose

- not a reducing sugar

- cleaved by sucrase

lactose

disaccharide of milk consisting of a glucose linked to a galactose at anomeric carbons via B-1,4-glycosidic linkage

- can be hydrolyzed via lactase or B-galactosidase (in bacteria)

- lack of lactase = lactose intolerance

maltose

beer

disaccharide resulting from hydrolysis of large oligosaccharides, consisting of two linked glucose molecules via a-1,4-glycosidic linkage

- hydrolyzed via maltase

human milk

>150 oligosaccharides in human milk protect newborn infants from infection bc they can't digest it

oligosaccharides serve as a fuel source for beneficial bacteria and prevent attachment of microbial pathogens to newborn's intestinal wall

storage of glucose

free glucose cannot be stored bc high concentrations will disturb the cell's osmatic balance. instead they have to be converted to glycogen and starch (polysaccharides)

polysaccharides (glycans and startch)

large polymeric oligosaccharides formed by the linkage of multiple monosaccharides. helps with energy storage and structural integrity

homopolymer

polymer in which all the monosaccharide units are the same

glycogen

large, branched homopolymer of glucose residues.

- most common homopolymer in animals

- storage form of glucose

- linked and branched via a-1,4-glycosidic linkage

- hydrolyzed via a-amylase

glycogen branching

increases SA to allow better access for enymes to rapidly breakdown glycogen

startch

homopolymer that serves as the nutritional resevoir in plants, hydrolyzed by a-amylase

two forms: amylose and amylopectin

amylose

unbranched (!) type of starch composed of glucose residues in a a-1,4-glycosidic linkage

amylopectin

branched (!) type of starch with ~1 a-1,6-linkage per 30 a-1,4-linkages

cellulose

unbranched polymer of glucose residues joined by B-1,4 linked

structural support, not nutritional

cellulose configuration benefits

the beta config allows cellulose to form long, straight chains that interact with one another through H bonding to yield a rigid, supportive structure

a linkages of glycogen and starch

form compact hollow cylinders suitable for accessible storage

can we digest cellulose

nope bc we don't have cellulase

insoluble fibers

increase the rate of absorption of digestion products and the speed at which products pass through the large intestine. bulks and soften stools

soluble fibers

slow the movement of food through the gastrointestinal tract and facilitates absoprtion of nutrients from the diet

chitin

homopolymer of B-1,4 linked N-acetylglucosamine

- found in fungal cell walls and arthropod exoskeletons

- crosslinked fibers composited with minerals and proteins to increase strength

uses of chitin

- carrier to assist drug delivery

- component of cosmetic and food products

- surgical dressing

glycoprotein

a carbohydrate group covalently attached to a protein

they make up 50% of the human proteome

important for cell adhesion

glycosylation

enzymatically adding sugar groups onto proteins. increases the complexity of the human proteome

proteoglycans

a carbohydrate with a protein component attached to it via glycosaminoglycan

important for structure and joint lubrication

mucins (mucoproteins)

central carbohydrate molecule with protein compotents that are heavily glycosylated by N-acetylgalactosamien at Ser and Thr residues

- mucus and lubricants

N-linkage of glycoproteins

links the sugars in glycoproteins to the amide nitrogen atom in the side chain of Asn

specific form of Asn needed for N-linkage

must be a part of an Asn-X-Ser or Asn-X-Thr sequences, where X is any residue EXCEPT Pro

O-linkage of glycoproteins

links the sugars in glycoproteins to the oxygen atom in the side chain of Ser or Thr

erythopoietin (EPO)

a glycoprotein secreted by the kidneys into the blood serum to stimulate production of RBCs

EPO fun facts

- cloned recombinant has helped anemia, but has also been abused by athletes

- glycosylation enhances the stability of the protein in blood

oligosaccharides on EPO

N-glycosylated at three Asn residues

O-glycosylated at a Ser residue

40% carbohydrate by weight

GlcNAcylation

the post translational, covalent attachment of a single N-acetylglucosamine to Ser or Thr residues

- reversible

- occurs when nutrients are abundant

- catalyzed via O-GlcNAc transferase

O-GlcNAc transferase

its GlcNAcylation sites are potential phosphorylation sites. could be involved in cross talk with protein kinases

improper regulation of O-GlcNAc transferase

insulin resistance

diabetes

cancer

neurological pathologies

proteoglycan composition

up to 95% glycosaminoglycans by weight, resembling polysaccharides more than proteins

glycosaminoglycans

long, unbranched polysaccharides composed of repeating units of disaccharides containing a derivative of an amino sugar

glycosaminoglycans sugars

the sugar derivative is either glucosamine or galactosamine

at least one of two sugars has a negative carboxylate or sulfate group

proteoglycan functions

- lubricants and structure in connective tissue

- mediate cell adhesion to ECM

- bind factors that regulate cell proliferation

inability to degrade glycosaminoglycans

causes diseases marked by skeletal deformities and reduced life expectancies

cartilage

contains the protein collagen and the proteoglycan aggrecan

aggrecan

large molecule with three globular domains

- glycosaminoglycans attach between G2 and G3

- G1 noncovalently binds to a central polymer of hyaluronate

water cushioning

water bound to glycosaminoglycans cushions compressive forces by being squeezed out when under pressure and rebinding when pressure is released

osteoarthritis

form of arthritis that results when water is lost from proteoglycan with aging

tandem repeats (VNTR) region

region of the protein backbone of mucins that is rich in O-glycosylated Ser and Thr residues

mucin functions

- adheres to epithelial cells and acts as a protective barrier

- hydrates the underlying cells

- plays a role in fertilization, immune response, and cell adhesion

overexpression of mucin

occurs in bronchitis, cystic fibrosis, and adenocarcinomas

ER and Golgi Complex

organelles that play central roles in protein trafficking

protein glycosylation location

N-linked glycosylation beings in the ER and continues in the Golgi

O-linked glycosylation occurs only in the Golgi

golgi complex

a stack of flattened membranous sacs. sends proteins to either lysosomes, secretory granules, or the plasma membrane, based on signals within their amino acid sequences and 3d structures

glycosyltransferases

catalyzes the formation of glycosidic linkages. most common carbohydrate donor is activated sugar nucleotides

blood groups

based on protein glycosylation pattterns (A, B, or O),

- all have a core O antigen

- A/B have one extra monosaccharide through an a-1,3 linkage to a galactose moiety of the O antigen

A antigen

type A transferase adds N-acetylgalactosamine to form the A antigen

B antigen

type B transferase adds galactose to form the B antigen

blood by enzymes present

O blood lacks both enzymes

AB has both

A has type A transferase

B has type B transferase

lysosomes

organelles that degrade and recycle cellular components or endocytosed material

i-cell disease

a lysosomal storage disease that causes severe psychomotor impairment and skeletal deformities.

- affected lysosomes contain undigested glycosaminoglycans and glycolipids

- active enzymes responsible for degredation are synthesizes but they lack appropriate glycosylation and are exported instead of delivered to lysosomes

biochemistry of i-cell disease

normally a mannose 6-phospahte residue of N-oligosaccharide will direct enzymes from golgi to lysosome, but in i-cell the mannose is missing a phosphate due to a deficiency of N-acetylglucosamine phosphotransferase

glycan-binding proteins

bind to specific carbohydrate structures on neighboring cell surfaces

lectins

class of glycan-binding proteins

ex. the mannose 6-phosphate receptor that binds and directs lysosomal enzymes to lysosomes

lectin functions

- facilitate cell to cell contact

- usually contain 2+ carbohydrate binding sites

- linked to carbohydrates by a number of weak noncovalent interactions

C-type lections

calcium requiring, found in animals

function in receptor-mediated endocytosis and cell-cell recognition

L-type lectins

rich in the seeds of legumes

serve as toxins for herbivores and acts as chaperones in the eukaryotic ER

C-type lection biochemistry

Ca2+ acts as a bridge between lectin and sugar, bound by two Glu residues. H bonds both between lectin side chains and carbohydrate