carbohydrates Flashcards
Describe the function and process of glycolysis.
- Catabolic pathway that saves some potential energy from glucose/G-6-P by forming ATP through substrate level phosphorylation
- Essentially the only way that energy can be made from fuel molecules when cells lack O2 (exercising muscle) or mitochondria (RBCs)
glucose has a ______ ending
OH (linear)
COOH at beginning
galactose has a _______ ending
CH2OH (linear)
COOH at beginning
fructose has a ______
singular O (pentagon shaped)
Disaccharides are formed from
monomers that are linked by glycosidic bonds.
A glycosidic bond is a type of covalent bond formed when hydroxyl group of one monosaccharide reacts with anomeric carbon of another monosaccharide
What’s an anomeric carbon?
Different anomers are mirror images of each other (left- and right-handed forms)
It is carbon #1 on the glucose residue
It stabilises the structure of glucose
Is the only residue that can be oxidised
Monosaccharides
cannot be hydrolysed into a simpler sugar.
3 hexoses in humans:
- glucose (glc)
- galactose (gal)
- fructose (fru)
3 disaccharides in humans:
- Maltose
- Lactose
- Sucrose
Maltose and diets
- Not much in our diets
- Breakdown product of starch
- Found in beer (starch of barley)
- Baby foods use it as natural sweetner
- Anomeric C1 available and so can be oxidised - reducing sugar
Lactose and diets
- Mainly found in milk
- Formed from a glycosidic (covalent) bond between galactose and glucose
- Anomeric C1 available and so can be oxidised - reducing sugar
Sucrose and diets
- Common (table) sugar
- Only made by plants
- Approx. 25% of dietary carbohydrate
- Sweetener in most processed food
- No anomeric C1 and so cannot be oxidised - non-reducing sugar
Polysaccharides and types
Polymers of medium to high molecular weight.
Homopolysaccharides
- Single monomeric species
Heteropolysaccharides
- Have two or more monomer species
how can polysaccharides be distinguished from each other
- Identity of their recurring monosaccharide units
- Length of their chains
- Types of bonds linking monosaccharide units
- Amount of branching they exhibit
Starch and types
Has many non-reducing ends and very few reducing ends
Contains two types of glucose polymer:
- Amylose (20-25% of starch)
- Amylopectin (75-80% of starch)
Amylose features
- D-glucose residues in (α1→4) linkage
- Can have thousands of glucose residues
- Form alpha helices
Account for 20-25% of starch
1,4 glycosidic bond is formed between
a hydroxyl oxygen atom on carbon-4 on one sugar (monosaccharide) and the α-anomeric form of C-1 on the other (monosaccharide).
Formed due to condensation reaction.
Amylopectin features
- Similar structure as amylose but branched
- Glycosidic (α1→4) bonds join glucose in the chains but branches (linkages) are (α1→6) and occur every 24 – 30 residues
- Form alpha helices
Account for 75-80% of starch
Glycogen in humans
- Animal cells use a similar strategy as plants to store glucose
- Polymer of glucose (α1→4) linked sub-units with (α1→6) branches every 8 to 12 residues
- This makes glycogen more extensively branched than starch
90% of glycogen is in:
Liver
- acts to replenish blood glucose when fasting
Skeletal muscle
- catabolism produces ATP for contraction
glycogen structure
- giant ball with protein in the middle
- surrounded by mitochondrion so we can use it for energy when needed
- highly packed glucose
Why store glucose in polymers?
- Compactness
- Amylopectin and glycogen have many non-reducing ends
- The polymers form hydrated gels and are not really “in solution”
many non reducing ends in glycogen and amylopectin allows them to:
- Be readily synthesised and degraded to and from monomers
- Thus speeds up the formation or degradation
As the polymers form hydrated gels and therefore are not really in solution this means:
- They are osmotically inactive
- If free glucose were in the cells then glucose would leave cell
- Either glucose would move out of the cell down the concentration gradient or the cell would use huge amounts of energy keeping it in the cell
Glycoproteins are
- Proteins that have carbohydrates covalently attached
- Most extracellular eukaryotic proteins have associated carbohydrate molecules
- Carbohydrate content varies between 1-80% by mass
Carbohydrates attached to proteins may:
- Increases the proteins solubility
- Influence protein folding and conformation
- Protect it from degradation
- Act as communication between cells
Glycosaminoglycans (GAGs) features
- Less commonly called mucopolysaccharides
- Found in mucus and also synovial fluid around the joints
- Un-branched polymers made from repeating units of hexuronic acid and an amino-sugar, which alternate through the chains
- contain groups NH, OSO3-, COO-
eg- hylaluronate, heparin, keratan sulphate
Proteoglycans features
- Formed from GAGs covalently attaching to proteins
- Macromolecules found on the surface of cells or in between cells in the extracellular matrix
- Form part of many connective tissues in the body
- COO- goes inside cell
EG- Syndecan, Glypican
Glycoproteins features
- Very similar to proteoglycans
- Usually found on the outer plasma membrane and extra cellular matrix,
- Also in blood and within cells in the secretory system (Golgi complex, secretory granules)
- Some cytoplasmic and nuclear proteins are also glycoproteins
Mucopolysaccharidoses is
- Group of genetic disorders caused by the absence or malfunction of enzymes required for the breakdown of glycosaminoglycans
- Over time the glycosoaminoglycans build up in connective tissue, blood and other cells of the body
- This build up damages cellular architecture and function
Mucopolysaccharidoses can cause
- Severe dementia
- Problems with the heart and any other endothelial structure as the glycosaminoglycans build up between the endothelial cells
- Bones tend to be stunted and joints will be inflammed and become severely damaged
- Hurler, Scheie, Hunter, Sanfilippo syndromes are all examples of mucopolysaccharidoses
Hurler syndrome causes
- Severe developmental defects:
- Stop developing at around 4 years
- Death at around 10 years old
- Clouding and degradation of the cornea
- Arterial wall thickening
- Dementia caused by, amongst other things:
- Build up of CSF
- Enlarged ventricular spaces
Experimental therapies currently include:
- Gene therapy - Enzyme replacement therapies
Carbohydrates in our diet
Starch
- Cereals, potatoes, rice
Glycogen
- Meat (however when the animal dies enzyme activity in tissue degrades much of the glycogen stores)
Cellulose and hemicellulose
- Plant cell walls – we don’t digest this
Oligosaccharides containing (α1→6) linked galactose
- Peas, beans, lentils – not digested
Lactose, sucrose, maltose
- Milk, table sugar, beer
Glucose, fructose
- Fruit, honey
Digestion of carbohydrates
Mouth:
- Salivary amylase hydrolyses (α1→4) bonds of starch
Stomach:
- No carbohydrate digestion
Duodenum (first part of the small intestine):
- Pancreatic amylase works as in mouth
Jejunum (second part of small intestine):
- Final digestion by mucosal cell-surface enzymes:
- Isomaltase – hydrolyses (α1→6) bonds
- Glucoamylase – removes Glc sequentially from non-reducing ends
- Sucrase – hydrolyses sucrose
- Lactase – hydrolyses lactose
Main products are – Glc, Gal, Fru
Absorption of glucose
- Glucose is absorbed through an indirect ATP-powered process
- ATP-driven Na+ pump maintains low cellular [Na+], so glucose can continually be moved into the epithelial cells
- This system continues to work even if glucose has to be moved into the epithelial cells against it’s concentration gradient (i.e. When blood glucose is high)
Absorption of galactose
Galactose has a similar mode of absorption as glucose, utilising gradients to facilitate it’s transport
Absorption of fructose
Fructose is slightly different,
- Binds to the channel protein GLUT5
- Simply moves down it’s concentration gradient (high in gut lumen, low in blood)
Cellulose and hemicellulose
Cannot be digested by the gut, but they do have a use
- Increase faecal bulk and decrease transit time
Lack of oligosaccharides in the diet can lead to poor health
- Many western diets
Polymers are broken down by gut bacteria
- Yielding CH4 (methane) and H2
- Beans will also have the same effect!
Disaccharidase deficiencies
Deficiencies may be genetic
Can result from,
- Severe intestinal infection
- Other inflammation of the gut lining
- Drugs injuring the gut wall
- Surgical removal of the intestine
Characterised by abdominal distension (enlargement) and cramps
Disaccharidase deficiencies diagnosis requires
enzyme tests of intestinal secretions.
Usually checking for lactase, maltase or sucrase activity
Lactose intolerance
- Most common disaccharidase deficiency
- Most humans lose lactase activity after weaning
- Western whites retain lactase activity into adulthood
- Theory that this comes from cattle domestication 100,000 years ago
If lactase is lacking, then ingestion of milk will give disaccharidase deficiency symptoms.
This happens for 2 reasons:
- Undigested lactose is broken down by gut bacteria causing gas build up and irritant acids
- Lactose is osmotically active, thus drawing water from the gut into the lumen causing diarrhoea
Symptoms can be avoided by,
- Avoiding milk products (many non-western diets do)
- Using milk products treated with fungal lactase
- Supplementing diet with lactase
Lactose intolerance facts
- Most common disaccharidase deficiency
- Most humans lose lactase activity after weaning
- Western whites retain lactase activity into adulthood
- Theory that this comes from cattle domestication 100,000 years ago
If lactase is lacking, then ingestion of milk will give disaccharidase deficiency symptoms.
This happens for 2 reasons:
- Undigested lactose is broken down by gut bacteria causing gas build up and irritant acids
- Lactose is osmotically active, thus drawing water from the gut into the lumen causing diarrhoea
Lactose intolerance symptoms can be avoided by:
- Avoiding milk products (many non-western diets do)
- Using milk products treated with fungal lactase
- Supplementing diet with lactase
Fate of absorbed Glucose
Glucose diffuses through the intestinal epithelium cells into the portal blood and on to the liver
Glucose is immediately phosphorylated into glucose 6-phosphate by the hepatocytes (or any other cell glucose enters)
Glucose 6-phosphate cannot diffuse out of the cell because GLUT transporters won’t recognise it
- This effectively traps the glucose in the cell
Enzyme catalyst,
- Glucokinase (liver) - Hexokinase (other tissues)
Glucokinase Km (affinity for substrate) and Vmax (efficiency of enzyme)
High Vmax so low affinity for substrate
High Vmax so very efficient enzyme
this is the opposite for hexokinase
When blood glucose is normal
the liver doesn’t “grab” all of the glucose, so other tissues have it.
Hexokinase does most of the work
When blood glucose is high (after meal)
liver “grabs” the Glucose.
Hexokinase is also working abut glucokinase takes care of all the extra glucose.
High glucokinase Vmax means
it can phosphorylate all that glucose quickly, thus most absorbed glucose is trapped in the liver
Hexokinase low Km means
even at low glucose tissues can “grab” glucose effectively
Hexokinase low Vmax means
tissues are “easily satisfied”, so don’t keep “grabbing” glucose
When blood glucose level falls, the liver
converts
When blood glucose level falls, the liver
converts glycogen to glucose-6-phosphate.
glucose-6-phosphate is broken down into glucose by glucose-6-phosphotase.
This process is called glycogenolysis.
When blood glucose level falls, the skeletal muscles
there is no Glucose-6-Phosphate and so are not directly available for blood glucose.
When doing exercise, glycogen is converted to G6P and through glycolysis this is converted to lactate.
the lactate is then converted into blood sugar in the liver
Synthesis of glycogen (Step 1)
- Glycogen does not form directly from Glucose monomers
- Glycogenin begins the process by covalently binding Glc from uracil-diphosphate (UDP)-glucose to form chains of approx. 8 Glc residues
- Then glycogen synthase takes over and extends the Glc chains
Synthesis of glycogen (Step 1)
- Glycogen does not form directly from Glucose monomers
- Glycogenin begins the process by covalently binding glucose from uracil-diphosphate (UDP)-glucose to form chains of approx. 8 glucose residues
- Then glycogen synthase takes over and extends the glucose chains
Synthesis of glycogen (Step 2)
The chains formed by glycogen synthase are then broken by glycogen-branching enzyme and re-attached via (α1→6) bonds to give branch points
Degradation (Mobilisation) of glycogen
- Glucose monomers are removed one at a time from the non-reducing ends as G-1-P
- Following removal of terminal Glucose residues to release G-1-P, by glycogen phosphorylase, Glucose near the branch is removed in a 2-step process by de-branching enzyme
- Transferase activity of de-branching enzyme removes a set of 3 Glucose residues and attaches them to the nearest non-reducing end via a (α1→4) bond
- Glucosidase activity then removes the final Glucose by breaking a (α1→6) linkage to release free Glucose
- This leaves an unbranched chain, which can be further degraded or built upon as needed
von Gierke’s disease and symptoms
Liver (and kidney, intestine) glucose 6-phosphatase deficiency
Symptoms:
- high [liver glycogen] – maintains it’s normal structure
- low [blood Glc] – fasting hypoglycaemia
- This is because glycogen cannot be used as an
energy source – all Glc must come from dietary
carbohydrate
- high [blood lactate] – lacticacidaemia
- Because the lactate produced by skeletal muscle
cannot be reconverted to Glc in the liver (this
process requires glucose 6-phosphatase – see Cori
cycle lectures)
von Gierke’s treatment
Treatment:
- Regular carbohydrate feeding – little and often
- Every 3-4 hours throughout the day and night
- Can be administered through a nasogastric tube
and pump, but sudden death has occurred when
the pump fails or the tube disconnects
McArdle’s disease and symptoms
Skeletal muscle phosphorylase deficiency
Symptoms:
- High [muscle glycogen] – maintains it’s correct
structure
- Weakness and cramps after exercise
- No increase in [blood glucose] after exercise
Most symptoms are not apparent in resting state, when
muscles will use other energy sources (Glc and fatty acids from the blood)
Usually becomes apparent in 20-30 year olds
- Children do suffer the disease but may remember pain
during adolescence and childhood
