Flashcards in Carbohydrates Deck (57):
What are the functions of carbohydrates?
Source of energy ("highly oxidisable")
Stores potential energy
Structural and protective functions
Contribute to cell-cell communication (blood groups)
What are the three important monosaccharide hexoses?
What are disaccharides and how are they formed?
• Formed from monomers that are linked by glycosidic bonds
– Covalent bond formed when hydroxyl group of one monosaccharide reacts with anomeric carbon of another monosaccharide
Name 3 important disaccharides in human biochemistry
– Maltose = glucose + glucose
– Lactose = glucose + galactose
– Sucrose = glucose + fructose
What disaccharide is found in beer, and is a break down product of starch in barley?
Describe and contrast the actions and functions of the enzymes hexokinase and glucokinase.
Glucokinase (liver) - high Km, high Vmax
Hexokinase (other tissues) - low Km, low Vmax
Why are lactose and maltose reducing sugars?
Anomeric carbon-1 on the glucose is available for oxidation
Whats the other name for starch?
What are the types types of glucose polymers that make up starch?
Amylose (20-25% of starch)
– D-glucose residues in straight (α1→4) linkage
– Can have thousands of glucose residues, linear and helical
Amylopectin (75-80% of starch)
– Similar structure as amylose but branched
– Glycosidic (α1→4) bonds join glucose in the chains but branches are (α1→6) and occur every 24 – 30 residues
Why do amylopectin and glycogen have many non-reducing ends?
This allows them to be readily synthesised and degraded to and from monomers respectively
What are the functions conveyed by the attachment of carbohydrates attached to proteins?
– Increases the proteins solubility
– Influence protein folding and conformation
– Protect it from degradation
– Act as communication between cells
What are glycosaminoglycans and what is their function?
Glycosaminoglycans (GAGs) are long unbranched polysaccharides consisting of a repeating disaccharide unit. The repeating unit (except for keratan) consists of an amino sugar along with a uronic sugar or galactose. Glycosaminoglycans are highly polar and attract water. They are therefore useful to the body as a lubricant or as a shock absorber, and are found in mucus and synovial fluids around joints.
Whats the difference between glycoproteins and proteoglycans?
Proteoglycans have more CHO than protein.
Both found on outer plasma membrane and in ECM, but glycoproteins are also found in the blood and within cells in the secretory system e.g. Golgi complex
What are proteoglycans?
• Formed from GAGs covalently attaching to proteins
• They are macromolecules found on the surface of cells or in between cells in the extracellular matrix
• Therefore form part of many connective tissues in the body
What are the mucopolysaccharidoses?
• Group of genetic disorders caused by the absence or malfunction of enzymes that are 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
• Can cause severe dementia, problems with the heart and any other endothelial structure as the glycosaminoglycans build up between the endothelial cells
• Also, bones tend to be stunted and joints will be inflammed and become severely damaged
Name some mucopolysacchairdoses
Hurler, Scheie, Hunter, Sanfilippo syndromes are all examples of mucopolysaccharidoses
What reaction does amylase catalyse?
Hydrolyses a1-4 bonds of starch
Where is amylase found?
Mouth - salivary amylase
Duodenum - panccreatic amylase
Where does digestion of CHOs take place to create free monosaccharides?
NOT IN STOMACH
What reaction does isomaltase catalyse?
Hydrolyses a1-6 bonds
What reaction does glucoamylase catalyse?
Removes glucose from non-reducing ends
What reaction does sucrase catalyse?
What reaction does lactase catalyse?
Describe the symptoms of Hurler syndrome
• Severe developmental defects:
• Clouding and degradation of the cornea
• Arterial wall thickening
• Dementia caused by, amongst other things:
– Build up of CSF
– Enlarged ventricular spaces
What two transporters are required for the absorption of glucose from the intestines into the blood?
Na+-glucose supporter into epithelial cells
GLUT2 uniporter into blood
How does the absorption of galactose and fructose compare to that of glucose?
Galactose is similar
Fructose binds to GLUT5 channel and moves down concentration gradient
What can cause disaccharide deficiencies
– Severe intestinal infection
– Other inflammation of the gut lining
– Drugs injuring the gut wall
– Surgical removal of the intestine
Can also be genetic
What are the symptoms of disaccharide deficiencies?
Characterised by abdominal distension and cramps
What is the most common disaccharide deficiency?
What does Km represent?
Affinity of an enzyme for its substrate, the lower the Km, the higher its affinity
What are the fates of glycogen in the liver and skeletal muscle when glucose levels in the blood drop?
In the liver, glycogen is broken down into glucose-6-phosphate and then into glucose via glucose-6-phosphatase and enters glycolysis.
In the muscle, where there is no glucose-6-phosphatase, G-6-P enters glycolysis to produce lactate
How is glycogen synthesised?
• Glycogenin begins the process by covalently binding Glucose from uracil-diphosphate (UDP)-glucose to form chains of approx. 8 Glc residues
• Then glycogen synthase takes over and extends the Glc chains
• The chains formed by glycogen synthase are then broken by glycogen-branching enzyme and re-attached via (α1→6) bonds to give branch points and create the highly branched glycogen structure:
What three enzymes are involved in glycogen synthesis?
Glycogen branching enzyme
Describe the degradation of glycogen to release glucose monomers
• Glucose monomers are removed one at a time from the non-reducing ends as G-1-P by glycogen phosphorylase
• 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
What three enzymes are involved in glycogen breakdown?
Debranching enzyme (transferase)
What is McArdles disease?
• Skeletal muscle phosphorylase deficiency
– High [muscle glycogen] – maintains it’s correct structure
– Weakness and cramps after exercise
– No increase in [blood glucose] after exercise
What is Von Gierkes disease?
Liver (and kidney, intestine) glucose 6-phosphatase deficiency
What is the 1st step of glycolysis?
Step 1 – Phosphorylation of glucose to G-6-P
• Catalyst – hexokinase
• Uses 1 ATP
• ΔG = -16.7 kJ/mol – essentially irreversible
What is the 2nd step of glycolysis?
Step 2 – Conversion of G-6-P to F-6-P
• Catalyst – phosphohexose isomerase
• ΔG = 1.7 kJ/mol – proceeds either way due to low free energy
What is the 3rd step of glycolysis?
Step 3 – Phosphorylation of F-6-P to F-1,6-bisphosphate
• Catalyst – phosphofructokinase-1 (PFK-1)
• Uses 1 ATP
• ΔG = -14.2 kJ/mol – essentially irreversible
• 1st “committed” step of glycolysis, because G-6-P and F-6-P can be used in other pathways, but F-1,6-bisP is solely destined for glycolysis
What is the 4th step of glycolysis?
Step 4 – Cleavage of F-1,6-bisphosphate to form glyceraldehyde 3- phosphate and dihydroxyacetone phosphate
• Catalyst – fructose 1,6-bisphosphate aldolase (or aldolase for short)
• ΔG = 23.8 kJ/mol – under cellular conditions the actual free energy change is small so the reaction is readily reversible
• This is the “splitting” part of glycolysis
• One glucose(6 C’s) is converted to two different 3C triose sugars
What is the 5th step of glycolysis?
Step 5 – Interconversion of triose sugar dihydroxyacetone phosphate to glyceraldehyde 3-phosphate
• Catalyst – triose phosphate isomerase
• ΔG = 7.5 kJ/mol – low, so readily reversible reaction
• Only G-3-P can participate in glycolysis, so the other 3 C sugar produced (dihydroxyacetone phosphate) is rapidly converted to G-3-P, thus yielding two G-3-P molecules for every one glucose
What three enzymes are involved in the fructose-1-phosphate pathway?
Fructokinase - fructose to fructose-1-phosphate
F-1-P aldolase - makes glyceraldehyde and dihydroxyacetonephosphate (glycolysis intermediate)
Triose kinase - converts glyceraldehyde into glyceraldehyde-3-phosphate (glycolysis intermediate)
Whats the function of the pentose phosphatase pathway?
• Produces NADPH for all organisms
• Produces pentoses (5-C sugars) which are precursors of ATP, RNA and DNA
Describe the two phases of the pentose phosphatase pathway
Oxidative, irreversible part
• Generates NADPH
• Converts G-6-P to a pentose phosphate
Reversible, non-oxidative part
• Interconverts G-6-P and pentose phosphate to form lots of different 3-, 4-, 5-, 6- and 7-C sugars
Describe black water fever
• G-6-P dehydrogenase deficiency:
– Genetic condition affecting 400 million people worldwide
• 1st step in the irreversible part of the P-P-P is catalysed by the enzyme G-6-P dehydrogenase
• Symptoms under certain conditions:
– Certain antibiotics
– After eating fava beans (divicine)
– Haemolytic anaemia – RBC’s burst, which darkens the urine with the iron they contain
• G-6-P dehydrogenase deficiency causes low RBC NADPH levels
• This allows damaging free radicals and H2O2 to build up, which damages the RBC membranes
What enters the citric acid cycle?
Where is the citric acid cycle controlled?
Entry of acetyl CoA - Pyruvate dehydrogenase is regulated by it’s immediate products and the end point of cellular respiration, ATP
First loss of C by isocitrate dehydrogenase
– As with pyruvate dehydrogenase, this enzyme is allosterically controlled through ATP and NADH concentrations
– ATP and NADH will negatively regulate
– ADP positive regulates
Second loss of C – α-ketoglutarate dehydrogenase
– Again, ATP and NADH negatively regulate
– Also, succinyl CoA negatively regulates
• These control points allow re-direction of cellular resources
When can pyruvate "enter" the citric acid cycle?
• As seen in gluconeogenesis, pyruvate can be converted to oxalocaetate by the enzyme pyruvate carboxylase
• Pyruvate carboxylase is only active when acetyl CoA is present, so a build up of acetyl CoA triggers this reaction
• This is known as an anaplerotic reaction (Greek origin, meaning to “fill up”) to allow more of the citric acid cycle to take place.
What is the initial fate of glucose when it enters cells?
Immediately converted to glucose-6-phosphate be hexokinase (or glucokinase in liver) to trap glucose in the cells as GLUT transporters no longer recognise it.
This can then be used for the pentose phosphate pathway, glycolysis and CAC, or for glycogen production, all depending on the needs of the cell.
What are the major carbohydrates in the diet? Briefly describe their structure and function
Lactose, sucrose and maltose
Starch (amylopectin and amylose)
Cellulose and hemicellulose
Oligosaccharides - not digested e.g. beans
Glucose and fructose
Describe the fate of blood lactate
Lactate from the muscle can be converted to glucose in the liver with the aid of glucose-6-phosphatase in the Cori cycle and gluconeogenesis if O2 is present
What is an important distinction between substrate level and respiration linked phosphorylation?
Substrate level requires soluble enzymes and chemical intermediates, while respiration linked involves membrane bound enzymes and gradients of proteins.
What no. glycolysis steps produce ATP?
Step 7 - G-3-P to 1,3-bisPG via G-3-P dehydrogenase
Step 10 - PEP to pyruvate via pyruvate kinase
Which reactions are irreversible in glycolysis?
1, 3 and 10
Requires lactate or pyruvate to form glucose when levels are low.
Occurs in cytosol and mitochondria
Set of 4 bypass reactions for the reverse of glycolysisto get around irreversible reactions
Pyruvate -> oxaloacetate
Oxaloacetate - > PEP
F-1,6-BP -> F-6-P
G-6-P -> glucose (can stay as G-6-P to trap it in cell or glucose can be made in lumina's of ER for transport out)