Describe some features of monosaccharides
3-9 carbons, commonly 3/5/6
Either aldose (C1 chiral) or ketose (C2 chiral)
Chiral carbon known as anomeric carbon and has two forms, alpha or beta
Enzymes can distinguish between the two
All but dihydroxyacetone have stereoisomers (D naturally occurring)
Exist largely as hemiactal ring structures (aldehyde/ketone group reacts with oxygen group of same sugar)
Partially oxidised (require less oxidation than fatty acids for complete oxidation)
How are disaccharides formed?
What bond is formed?
What are the 3 major dietary disaccharides?
Sucrose (glucose - fructose
)Lactose (glucose - glactose)
Maltose (glucose - glucose)
Name 4 common polysaccharides of glucose and include what type of linkages are found in each.
Glycogen (1-4, 1-6)
Amylopectin (1-4, 1-6)
Cellulose (beta 1-4)
Why is cellulose indigestible?
Humans do not have the required enzymes to break beta 1-4 glycosidic bonds
What two polysaccharides are found in starch?
How and where are polysaccharides broken down?
What are they broken down into at first?
Salivary amylase in mouth, pancreatic amylase in duodenum
Broken down to glucose, maltose and other small polysaccharides (dextrins)
How are broken down polysaccharides further digested?
Hint: Where? What is released? What enzymes involved?
Maltose, dextrins and disaccharides broken down in duodenum and jejunum
Large glycoproteins complexes on microvilli brush borders
Key enzymes are:
Releases glucose, galactose and fructose
Where is major site of galactose and fructose metabolism?
What can be said about glucose concentration in the blood?
Must be kept constant due to an absolute requirement for it by certain tissues
What are the tissues that have an absolute requirement for glucose and what is their overall glucose requirement per day?
RBCs, WBCs, kidney medulla, lens of the eye
What is the overall glucose requirement per day?
180g per day
What is the daily requirement of the CNS for glucose?
140g per day
How many enzymes are involved in glycolysis?
Where does glycolysis occur?
What is generated by glycolysis?
Useful intermediate compounds (C3)
What are the key features of glycolysis?
No loss of CO2
All intermediates phosphorylated and can in turn phosphorylate ADP
2 moles of ATP required per mole of glucose, 4 produced, 2 net produced
What 3 steps of glycolysis are irreversible and what enzymes are they catalysed by?
1 - hexokinase (in liver glucokinase)
3 - phosphofructokinase-1
10 - pyruvate kinase
When there is not enough oxygen supply to a cell or a cell has no mitochondria how is ATP produced?
Reduction of pyruvate to lactate
What enzyme is involved in the pyruvate to lactate reaction?
What is the equation for the reduction of pyruvate to lactate?
2 pyruvate + 2 NADH + 2 H+ ---> 2 lactate + 2 NAD+
What is the overall equation of anaerobic glycolysis?
Glucose + 2 Pi + 2 ADP ---> 2 Lactate + 2 ATP + 2 H2O
What happens to lactate after it's production in tissues?
Released into blood stream
Converted back to pyruvate in cardiac muscle
Then oxidised to CO2
Converted back to glucose in liver
What effect does Lactate dehydrogenase have on NAD+ conc?
Increases NAD+ conc in anaerobic conditions
What is the normal level of lactate in the bloodstream?
What can increase the level of lactate production and hence it's conc in the blood plasma?
What is the renal threshold for lactate and if exceeded what is the effect?
>5mM and exceeds renal threshold, causing lactic acidosis as the buffering capacity of blood plasma is exceeded
How does lactose intolerance come about?
Low activity of lactase enzymes meaning lactose cannot be digested.
What is the overall equation for galactose metabolism to glucose-6-phosphate and where does this reaction chain occur?
Galactose + ATP ----> G-6-P + ADP
In the case of Galactosemia what is the effect on metabolism and how does this come about?
Cannot metabolise galactose
Missing galactokinase or galactose-1-phosphate uridyltransferase enzymes
Which of the 2 enzymes is it rarer to have missing in Galactosemia and what is the difference between the effects of missing either enzyme?
Galactokinase rarer to have absent
Causes build up of galactose in tissues
G-1-P Uridyltransferase more common to have missing however G-1-P builds up in tissues too (is more hepatotoxic)
When galactose builds up in galactosaemic patients what is it metabolised into and by what enzyme?
What is the knock on metabolic effect of this?
Depletes NADPH in some tissues
What are the clinical consequences of NADPH depletion in some tissues of a galactosemic patient and how do they come about?
Lens of eye damaged by -S-S- bonds formed in absence of NADPH cross linking of proteins causes cataracts
Random glycosylation of lens proteins may also contribute to cataracts
Intraocular pressure rises (glaucoma) due to accumulation of galactose and Galactitol.
G-1-P accumulation leads to damage of liver, kidney and brain, this could be caused by sequestration of Pi by G-1-P
In what tissues is the pentose phosphate pathway important?
Liver, RBCs, adipose tissue
What are the major functions of the pentose phosphate pathway?
Produce NADPH in the cytoplasm
Provides reducing power for lipid synthesis
Maintains free -SH groups in haemoglobin in RBCs
Used in various detox mechanisms
Produces C5 ribose for the synthesis of nucleotides
Why does the pentose phosphate pathway have a high activity in dividing tissue?
Produces ribose sugars for use in nucleotides
Is the pentose phosphate pathway oxidative or reductive overall?
Oxidative, no ATP and some CO2 formed
Describe phase 1 of the pentose phosphate pathway, give an equation.
G-6-P is oxidised and decarboxylated by G-6-P dehydrogenase and 6-phosphogluconate dehydrogenase in a reaction requiring NADP
G-6-P + 2 NADP --> ribose phosphate + 2 NADPH + 2 CO2 + 2 H+
Describe phase 2 of the pentose phosphate pathway, give an equation.
Complex series of reactions converting any unused C5 sugars to glycolysis intermediates
3 C5 sugar phosphate --> 2 fructose-6-phosphate + glyceraldehyde-3-phosphate
When NADPH is depleted in an rbc what can happen to haemoglobin?
Can form insoluble polymers (Heinz bodies) due to cysteine cross linkage (disulphide bridges)
What is the rate limiting enzyme for the pentose phosphate pathway?
Deficiency in G-6-P dehydrogenase is caused by what type of genetic mutation?
X linked point mutation
Mutation of G-6-P dehydrogenase has what effect on its function and leads to low levels of?
Low levels of NADPH
Formation of Heinz bodies in RBCs leads to what?
Pyruvate is converted to acetylCoA by what enzyme?
What is significant about the action of pyruvate dehydrogenase in terms of reversibility and acetylCoA's use in gluconeogenesis?
Irreversible reaction meaning loss of CO2 from pyruvate is irreversible and hence acetylCoA cannot be converted back to pyruvate for use in gluconeogenesis.
Explain the 3 methods of pyruvate dehydrogenase control.
AcetylCoA allosterically inhibits Pyruvate Dehydrogenase
ATP/NADH inhibit and ADP promotes allosterically
Activated when there's plenty of glucose to be catabolised (activated by insulin)