1
Q
give some general features of carbohydrates (4)
A
- are highly oxidizable (hence are a major energy source)
- function to store potential energy (starch in plants, glycogen in animals)
- have structural and protective functions (plant cell walls, extracellular matrices in animal cells)
- contribute to cell-cell communication (ABO blood groups)
2
Q
describe the structure of a monosaccharide and give examples (3)
A
monosaccharides are hexoses (6-C sugars)
- glucose (Glc)
- galactose (Gal)
- fructose (Fru)
3
Q
describe the structure of a disaccharide and give examples (3)
A
formed from monomers that are linked by glycosidic bonds
- maltose
- lactose
- sucrose
4
Q
what is a glycosidic bond?
A
the covalent bond formed when hydroxyl group of one monosaccharide reacts with anomeric carbon of another monosaccharide
5
Q
is maltose a reducing sugar?
A
yes, anomeric CC-1 is available for oxidation
6
Q
how is lactose formed, and is it a reducing sugar?
A
formed from a glycosidic bond between Gal and Glc
7
Q
is sucrose a reducing sugar?
A
no, since no free anomeric C-1. is non-reducing.
8
Q
describe the structure of a polysaccharide and the two different types
A
- polymers of medium to high molecular weight
- distinguished by their monosaccharide units, the length of their chains, the types of bonds between units and amount of branching
- homopolysaccharides: single monomeric species
- heteropolysaccharides: have two or more monomer species
9
Q
starch contains two types of glucose polymer, what are they?
A
- amylose: d-glucose residues in (α1→4) linkage; can have thousands
- amylopectin: similar structure to amylose but branched; glycosidic (α1→4) bonds join glucose in the chains but branches are (α1→6) and occur every 24 – 30 residues
10
Q
what is the structure of glycogen?
A
glycogen is a storage molecule and is a polymer of glucose (α1→4) linked sub-units with (α1→6) branches every 8 to 12 residues
11
Q
what are the main sites of glycogen storage and its’ functions there?
A
- liver: acts to replenish blood glucose when fasting
- skeletal muscle: catabolism produces ATP for constriction
12
Q
why is glucose stored in polymers?
A
- compactness
- amylopectin and glycogen have many non-reducing ends (hence can be readily synthesised/degraded from/to monomers)
- polymers form hydrated gels and are not really “in solution”
13
Q
what are glycoproteins and what properties do they have?
A
- proteins that have carbohydrates covalently attached
- carbohydrate attachment to proteins may: increase the proteins’ solubility; influence protein folding and conformation; protect it fro degradation; act as communication between cells
14
Q
what are glycosaminoglycans (GAGs) and where are they found?
A
- Un-branched polymers made from repeating units of hexuronic acid and an amino-sugar, which alternate through the chains
- found in mucus and synovial fluid around the joints
15
Q
what are proteoglycans and where are they found?
A
-formed from GAGs covalently attaching to proteins
- found on the surface of cells or in between cells in the extracellular matrix
- therefore form part of many connective tissues in the body
16
Q
where are glycoproteins usually found?
A
- usually found on the outer plasma membrane and ECM, but also in the blood and within cells in the secretory system (Golgi complex, secretory granules)
- some cytoplasmic and nuclear proteins are also glycoproteins
17
Q
what are mucopolysaccharidoses and how to they occur?
A
- they are a group of genetic disorders caused buy the absence or malfunction of enzymes that are required to break down glycosaminoglycans
- over time, GAGs build up in connective tissue, blood and other cells of the body, damaging cellular structure and function
18
Q
give an example of a mucopolysaccharidose disease and describe its’ symptoms
A
-hurler syndrome:
severe developmental defects, clouding and degradation of the cornea, arterial wall thickening, dementia (build up of CSF, enlarged ventricular spaces)
19
Q
what are the mechanisms of CARBOHYDRATE digestion and where do they occur?
A
mouth: salivary amylase hydrolyses (α1→4) bonds of starch
stomach: NO carb digestion
duodenum: pancreatic amylase works as in the mouth
jejunum:
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
20
Q
describe the mechanism of glucose absorption at the epithelial cells
A
indirect ATP-powered process
glucose in the lumen of the small intestine is transferred across the apical membrane via a Glu/Na+ symporter that requires that 2Na+ bind, driven by high extracellular [Na+]
in the epithelial cell, low Na+ and high K+ drives transfer of 2K+ into the cell and 3Na+ out (Na/K Pump), and the glucose molecule is transported into the blood by a glucose uniporter, GLUT2, which facilitates downhill efflux.
21
Q
what are the mechanisms of absorption of other monosaccharides, Gal and Fru?
A
galactose is similar as glucose; uses gradients to facilitate its’ transport
fructose binds to the channel protein GLUT5 and simply moves down its’ concentration gradient (high in gut lumen and low in the blood)
22
Q
what use do cellulose and hemicellulose have?
A
they cannot be digested by the gut, but do help to increase faecal bulk and decrease transit time.
a lack of oligosaccharides in the diet is bad for health
polymers are broken down by gut bacteria to yield CH4 and H2
23
Q
what may cause disaccharide deficiencies and how are they diagnosed?
A
- may be genetic
- can result from: severe intestinal infection, other gut lining inflammation, drugs injuring the gut wall, surgical removal of the intestine
- they are characterised by abdominal distension and cramps
- diagnosis: enzyme tests usually checking for lactase, maltase or sucrase activity
24
Q
lactose intolerance/lactase deficiency can cause disaccharide deficiency symptoms; what are the reasons for this? (2)
A
- 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
25
what happens to glucose after it has been absorbed/diffused 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)
26
glucokinase has a high Km for glucose and high Vmax, hexokinase has a low Vmax and Km for glucose. what does this mean when blood Glc is high (i.e. after a meal)?
- Blood [Glc] normal – the liver doesn’t “grab” all of the glucose, 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 even at low [Glc] tissues can “grab” Glc effectively
- Hexokinase low Vmax means tissues are “easily satisfied”, so don’t keep “grabbing” Glc
27
what does it mean if an enzyme has a high Vmax?
it means that the enzyme is efficient
28
what does it mean if an enzyme has a low Km?
it means it has a high affinity for its' substrate
29
glucose converts into glucose-6-phosphate via hexokinase. what are the possible fates for G-6-P in the liver and other tissues?
- can go through the pentose phosphate pathway to form pentoses and NADHP
- can go through glycolysis (forming ATP via substrate-level phosphorylation) and can continue on to form pyruvate and enter into TCA to produce much ATP via oxidative phosphorylation
- can be converted for into glycogen (stored in the liver or skeletal muscle) to be mobilised when needed
30
glycogen is a storage molecule found mainly in the liver and skeletal muscle. what are its conversion pathways to glucose in these two areas?
liver: glycogen→ G-1-P →
G-6-P→(glucose-6-phosphatase enzyme acts on G-6-P)→
glucose in blood
skeletal muscle; there is no glucose 6-phosphatase:
glycogen→ G-1-P → G-6-P →
(glycolysis/substrate level phosphorylation takes place)→
lactate
(=ATP for muscle contraction fro glycolysis)
31
describe the steps of the synthesis of 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
- 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
32
how is glycogen degraded/mobilised?
- Glc monomers are removed one at a time from the non-reducing ends as G-1-P
- Glycogen phosphorylase produces from single monomer a molecule of glucose-1-phosphate
- Transferase activity of de-branching enzyme removes a set of 3 Glc residues and attaches them to the nearest non-reducing end via a (α1→4) bond
- Glucosidase activity then removes the final Glc by breaking a (α1→6) linkage to release free Glc
33
describe the mechanism, symptoms and treatment for Von Gierke's disease
- Liver (and kidney, intestine) glucose 6-phosphatase deficiency
- symptoms: high [liver glycogen], low [blood glucose] - fasting hypoglycaemia, high [blood lactate] - lacticacidaemia
- treatment: regular carbohydrate feeding, little and often
34
describe the mechanism, symptoms and treatment for McArdle's disease
- skeletal muscle glycogen phosphorylase deficiency
- symptoms: high [muscle glycogen], weakness + cramps after exercise, no increase in [blood glucose] after exercise (all not usually apparent when in resting state!)
- treatment: avoid strenuous activity, make use of your “second wind”
35
what is glycolysis? (generally)
- it is a catabolic pathway that saves some potential energy from glucose/G-6-P by forming ATP through substrate level phosphorylation
- is essentially the only way that energy can be made from fuel molecules when cells lack O2 (exercising muscle) or mitochondria (RBCs)
36
how many ATP are produced in the "preparatory phase" of glycolysis?
2ATP for each glucose molecule
37
how many aTP are produced in the "payoff phase" of glycolysis?
4ATP, therefore there is an overall gain of 2ATP (and NADH) per glucose molecule for the entire glycolysis process.
38
what is step 1 of glycolysis, what catalyst is used and is it reversible?
phosphyrolation of glucose: glucose → G-6-P
hexokinase catalyst
irreversible
39
what is step 2 of glycolysis, what catalyst is used and is it reversible?
G-6-P → F-6-P (conversion)
phosphohexose isomerase catalyst
reversible
40
what is step 3 of glycolysis, what catalyst is used and is it reversible?
F-6-P → F-1,6-bisP (phosphorylation)
phosphofructokinase-1 (PRK-1)
irreversible and first "committed" step of glycolysis
41
what is step 4 of glycolysis, what catalyst is used and is it reversible?
F-1,6-bisP is cleaved
fructose 1,6-bisphosphate aldolase (aldolase)
reversible, this is the "splitting part of glycolysis)
42
what is step 5 of glycolysis, what catalyst is used and is it reversible?
interconversion of triose sugars (since only G-3-P can participate in glycolysis, not DHAP)
triose phosphate isomerase catalyst
reversible
43
what is step 6 of glycolysis, what catalyst is used and is it reversible?
G-3-P → 1,3-bisPG (oxidation)
glyceraldehyde 3-phosphate dehydrogenase
2NADH produced
44
what is step 7 of glycolysis, what catalyst is used and is it reversible?
Phosphate transfer from 1,3-bisPG to ADP
phosphoglygerate kinase enzyme
2ATP produced
a substrate-level phosphorylation reaction
45
what is step 8 of glycolysis, what catalyst is used and is it reversible?
3-PG → 2-PG (conversion)
phosphoglycerate mutase enzyme
reversible
46
what is step 9 of glycolysis, what catalyst is used and is it reversible?
2-PG → PEP (dehydration)
enolase catalyst
reversible
47
what is step 10 of glycolysis, what catalyst is used and is it reversible?
Phosphate transfer from PEP to ADP
pyruvate kinase enzyme
2ATP produced
final step which produces pyruvate
48
NAD+ needs to be regenerated throughout glycolysis otherwise it cannot occur. since NAD+ is limited in the cell, how does this occur?
production of pyruvate in different fates uses NADH which produces NADH+ and this is recycled back into glycolysis for use over and over again
= redox balance
49
what are the 2 steps in production of ethanol from pyruvate?
pyruvate →(pyruvate decarboxylase enzyme)→ acetaldehyde→(alcohol dehydrogenase enzyme)→ ethanol
(acetaldehyde → ethanol step produces NAD+ which is recycled into glycolysis under anaerobic conditions)
50
what step converts pyruvate to l-lactate?
pyruvate →(lactate dehydrogenase)(NAD+)→ lactate
occurs in human cells lacking oxygen
51
what step converts pyruvate to acetyl CoA?
pyruvate →(pyruvate dehydrogenase complex)→ acetyl CoA
in cells with access to oxygen
occurs within the mitochondria of cels
NADH formed in this reaction that will later give up its hydride ion
last step of glycolysis
52
what is the cori cycle and when does it occur?
when muscles lack oxygen, ATP is made through substrate-level, rather than oxidative, phosphorylation; this produces lactate, which is converted to Glc in the liver via gluconeogenesis.
the liver repays the oxygen debt run up by the muscles; this interaction between the liver and muscle is called the CORI CYCLE.
53
define gluconeogenesis
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates.
54
why is gluconeogenesis not the reverse of glycolysis?
3/10 glycolysis reactions are unable to be reversed due to large –ve ΔG
the cell passes these reactions with enzymes that catalyse a separate set of irreversible reactions
55
there are 4 bypass reactions to sidestep the 3 irreversible glycolysis reactions. what does this allow to happen?
- allows for independent control of the glycolysis and gluconeogenesis pathways
- also prevents them cancelling one another out
56
what is gluconeogenesis bypass reaction A?
Pyruvate to Phosphoenolpyruvate (PEP)
57
what is gluconeogenesis bypass reaction C?
Fructose-1,6-bisphosphate to Fructose-6-phosphate
fructose 1,6-bisphosphatase enzyme
58
what is gluconeogenesis bypass reaction B?
oxaloacetate to PEP
59
what is gluconeogenesis bypass reaction D?
glucose-6-phosphate to glucose
glucose 6-phosphatase
60
F-6-P is readily converted to G-6-P, which is usually the end point for gluconeogensis. where does formation of free Glc occur?
- free Glc is not made in the cytoplasm, but in the lumen of the endoplasmic reticulum
- It requires the G-6-P to be shuttled into the lumen and the Glc to be shuttled back out to the cytoplasm
61
what happens to fructose and galactose once ingested?
the body does not have catabolism pathways for either sugar, so they an both enter glycolysis at various points.
most fructose is metabolised by the liver
62
what is the mechanism of the fructose 1-phosphate pathway?
uses 1 or 2 ATP for each Fru molecule converted
fructose →(fructokinase)→ fructose 1-phosphate →(fructose 1-phosphate aldolase)→ glyceraldehyde + dihydroxyacetone phosphate →(triode kinase)→ glyceraldehyde 3-phosphate
remember enzymes mainly!!
63
how is galactose metabolised?
galactose → G-1-P via a UDP-galactose
UDP-glucose and UDP-galactose amounts remain unchanged as they are recycled, so net gain of reaction is G-1-P
64
what is the purpose of the pentose phosphate pathway? (3)
produces NADPH for all organisms:
- liver (fatty acid synthesis, steroid synthesis, drug metabolism)
- mammary gland (fatty acid synthesis)
- adrenal cortex (steroid synthesis)
- RBCs (as an antioxidant)
produces pentoses (5-C sugars; are precursors of ATP, RNA and DNA)
metabolises the small amount of pentoses in the diet
65
what are the two phases of the pentose-phosphate 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 to 7-C sugars)
66
what are the differences and similarities between NADP+ and NAD+?
- both used as electron carriers
- NAD+ is used in metabolism of dietary sugars in the redox reactions of glycolysis and TCA whereas NADP+ is used in anabolism to convert simple precursors into things like fatty acids (can also act as an antioxidant)
- enzymes involved in both catabolic and anabolic pathways have different specificities for each; stops one electron carrier being used in the wrong type of pathway
67
what is black water fever?
a G-6-P dehydrogenase deficiency (genetic condition)
the first part of the PPP is catalysed by this enzyme
causes low RBC NADHP levels which allows damaging free radicals to bold up and damage RBC membranes
[carriers are resistant to malaria as in SCA]
68
mouse experiment thing: what does PEPCK over expression cause?
(results from lots of exercise)
- lots of PEP in muscle from lactate
- PEP then enters TCA by forming pyruvate
- therefore lactate from exercising muscles allows ATP to be provided for muscle function
69
what does the citric acid metabolise and where does it occur?
- metabolises all "fuel" molecules; carbohydrate, fatty acids and amino acids
- occurs in the mitochondrial matrix
- is part of catabolic processes and produces large amounts of ATP indirectly
- removes electrons and passes them on to form NADH and FADH2
70
how and where is Acetyl CoA made?
Pyruvate from glycolysis and fatty acids are oxidised further to acetyl CoA in the mitochondrial matrix
acetyl coA is made through the action of the enzyme pyruvate dehydrogenase
71
describe the structure of pyruvate dehydrogenase
- contains tens of copies of each enzyme sub-unit
| - each subunit catalyses a different part of the reaction to convert pyruvate to acetyl CoA
72
describe the purpose of the first 3 enzyme subunits of pyruvate dehydrogenase when it acts on pyruvate
- E1 catalyses the first decarboxylation of pyruvate
- E2 transfers the acetyl group to coenzyme A
- E3 recycles the lipoyllysine through the reduction of FAD, which is recyled by passing electrons to NAD+
73
how is entry to the citric acid cycle controlled?
pyruvate dehydrogenase (PDH), the enzyme which converts pyruvate to Acetyl CoA, is regulated by its' immediate products, and ATP
is inhibited (if cell has enough energy) by acetyl coA, NADH, ATP
is driven (if the cell needs more energy/more TCA action) by pyruvate and ADP
74
there are two other points of control at non-reversible/exergonic steps of TCA. what are they and how do they work?
1. isocitrate dehydrogenase
- allosterically controlled via ATP + NADH conc. (negatively regulate, positively regulated by ADP)
2. α-ketoglutarate dehydrogenase
- again, ATP and NADH negatively regulate
- also, succinyl CoA negatively regulates
75
the citric acid cycle is an AMPHIBOLIC pathway. what does this mean?
it serves both catabolic and anabolic processes
76
the citric acid cycle can also provide biosynthetic precursors. describe how this may arise.
When cellular energy needs are met through the citric acid cycle, it can produce the building blocks of nucleotide bases, heme groups and proteins
this does, however, deplete the cell of TCA intermediates
77
what is an anaplerotic reaction?
anaplerotic reactions are chemical reactions that form intermediates of a metabolic pathway.
(r.m) science for medicine
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