Carbohydrates IA %% (+ Flashcards
Carbohydrate facts
Highly oxidizable
–Sugar and starch molecules have “high energy” H atom-associated electrons
–Thus they are a major energy source
–Carbohydrate catabolism is the major metabolic process for most organisms
Function to store potential energy
–Starch in plants
–Glycogen in animals
Have structural and protective functions
–In plant cell walls
–Extra cellular matrices of animal cells
Contribute to cell-cell communication
–ABO blood groups
3 Monosaccharides examples
–Glucose (Glc)
–Galactose (Gal)
–Fructose (Fru)
Disaccharides
- 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
- Maltose = glu + glu. Found in baby food
- Lactose= glu + galactose. Milk
- Sucrose= glu + fruc. Table sugar
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
Polysaccharides
•Distinguished from each other in the:
–identity of their recurring monosaccharide units
–length of their chains
–types of bonds linking monosaccharide units
–amount of branching they exhibit
Homopolysaccharides:Single monomeric species
Heteropolysaccharides:Have two or more monomer species
Starch
Has many non-reducing ends and very few reducing ends
Contains 2 types of glucose polymer:
Amylose (20-25% of starch)
–D-glucose residues in (α1→4) linkage
–Can have thousands of glucose residues
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
Glycogen
- 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 (amylopectin)
Glycosaminoglycans (GAGs)
- aka mucopolysaccharides
- Hints at their function – 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
Proteoglycans
- Carbohydrate > protein
- 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
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
- Hurler, Scheie, Hunter, Sanfilippo syndromes are all examples of mucopolysaccharidoses
Carb digestion diagram
Monosaccharide digestion
- Glucose is absorbed through an indirect ATP-powered process
- ATP-driven Na/K pump maintains low cellular [Na+], so glucose can continually be moved in to 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)
- Galactose has a similar mode of absorption as glucose, utilising gradients to facilitate it’s transport
- 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
•These 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 and H2
•Beans will also have the same effect!
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
Lactose intolerance symptoms relief strategies
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 Glc
- Glc diffuses through the intestinal epithelium cells into the portal blood and on to the liver
- Glc 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)
- Blood [Glc] normal – the liver doesn’t “grab” all of the glucose, (as high Km means low affinity) so other tissues have it
- Blood [Glc] high (after meal) - liver “grabs” the Glc
- High glucokinase Vmax means it can phosphorylate all that Glc quickly, thus most absorbed Glc is trapped in the liver
- Hexokinase low Km means, high affinity, so even at low [Glc] tissues can “grab” Glc effectively
- Hexokinase low Vmax (so slow reaction rate) means tissues are “easily satisfied”, so don’t keep “grabbing” Glc
Diagram 1
Diagram 2
Glycogen synthesis 1
- Glycogen does not form directly from Glc monomers
- Glycogenin begins the process by covalently binding Glc from uracil-diphosphate (UDP)-glucose to form chains of approx. 8 Glc residues
Glycogen synthesis 2
- 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
Diagram 3
Von Gierke’s disease
•Liver (and kidney, intestine) glucose 6-phosphatase deficiency (G-6-P ⇒ Glc)
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 )
Treatment:
–Regular carbohydrate feeding – little and often (every 3-4 hours 24/7)
–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
Skeletal muscle phosphorylase deficiency (add Phosphate)
•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
Treatment:
–Avoid strenuous activity
–Make use of your “second wind”
–Exercise briefly (anaerobically), wait for the pain to subside, continue to exercise (aerobically using oxidative phosphorylation of fatty acids)
Glycolysis
NAD+ regeneration
- No NAD+ = no glycolysis
- NAD+ limited in the cell – comes from niacin (essential vitamin)
- Note: Pic below is for exercising muscle that produces lactate from the pyruvate, but pyruvate can have other fates
- All of these fates will produce NAD+ to replenish the NAD+ required for reduction of various intermediate metabolites
- This is termed redox balance
Diagram 4
Pyruvate ⇒ ethanol►
Yeast and several other microorganisms can generate ethanol from pyruvate
•2-step process:
–Pyruvate decarboxylase
–Alcohol dehydrogenase
Pyruvate ⇒ lactate►
- Occurs In human cells lacking O2 e.g Vigorously exercising muscle
- Also in RBC’s – lack mitochondria
- Pyruvate is reduced to lactate via fermentation
- Oxidation of NADH drives the reduction of pyruvate to lactate, which in turn replenishes stores of NAD+ for further glycolysis
Cori cycle
- When we sprint, muscles don’t receive O2 fast enough to make ATP via oxidative phosphorylation
- Instead ATP is made via substrate-level phosphorylation, producing lactate
- Lactate is converted to Glc in the liver by a process called gluconeogensis
- The liver repays the oxygen debt run up by the muscles
- This interaction between the liver and muscle is called the Cori cycle
Gluconeogenisis is not the reverse of glycolysis
- 7 out of 10 glycolysis reactions are reversible
- Large –ve ΔG prevents the 3 reactions being reversible
- The cell bypasses these reactions with enzymes that catalyse a separate set of irreversible reactions
- This causes glycolysis and gluconeogenesis to be irreversible processes
Bypass reactions
- 4 reactions that sidestep the 3 irreversible reactions of glycolysis
- This allows for independent control of the glycolysis and gluconeogenesis pathways
- Also prevents them cancelling each other out
- Utilise the cytosol (rxns C & D) and also the mitochondria (rxns A & B)
•
Reactions A & B
Reaction C
Reaction D
Glycolysis with Fructose & Galactose
NADP+ vs NAD+
- NADP+ is used in exactly the same way as NAD+ - an electron carrier
- NAD+ is used in metabolism of dietary sugars in the redox reactions of glycolysis and the citric acid cycle
- NADP<strong>+</strong> is used in anabolism to convert simple precursors into things like fatty acids – NADP+ also acts as an antioxidant
- Enzymes involved in both metabolic and anabolic pathways have differing specificities for these two electron carriers, which stops NADP+ being used for metabolism and vice versa
Reduced gluconeogenesis (pished)
- Liver needs all of the NAD+ for gluconeogenesis
- So drinking inhibits gluconeogenesis
- Leads to:
–lacticacidaemia (increased [blood lactate])
–hypoglycaemia (decreased [blood Glc])
•And when untreated:
–confusion → loss of consciousness → death!
•Particularly bad if you’re athletic ot dieting
Acetyl CoA
- Pyruvate from glycolysis and fatty acids are oxidised further to acetyl CoA in the mitochondrial matrix
- Acetyl CoA sits in the centre of energy production for the cell as it allows different intermediates into the main energy producing pathway of the citric acid cycle
Acetyl CoA formation?
- From pyruvate, through the action of the enzyme pyruvate dehydrogenase
- Very complicated series of reactions involving decarboxylation of the pyruvate molecule, then oxidation, followed by transfer of the CoA complex
- The decarboxylation step releases 2 electrons (in the form of 2 H+), which can pass to O<strong>2</strong> to produce more ATP through NADH intermediates
Simplified Citric acid diagram
Pentose-phosphate pathway►
•Produces NADPH for all organisms
- LIVER – fatty acid synthesis, steroid synthesis and drug metabolism
- MAMMARY GLAND – fatty acid synthesis
- ADRENAL CORTEX – steroid synthesis
- RED BLOOD CELLS – as an antioxidant
- Produces pentoses (5-C sugars), these are precursors of ATP, RNA and DNA
- Metabolises the small amount of pentose’s in the diet. Usually dietary pentose’s come from digestion of nucleotides
