Carbohydrates II Flashcards
What is a rate-limiting Enzyme
Enzymes with the lowest Catalytic Activity,
Often the metabolic pathways are controlled by the rate of the “rate-limiting enzyme”
What is the potential site of regulation
- Irreversible steps are potential sites of regulation
- Reduced activity reduces the flux of substrates through the pathway directly
- Reducing levels of product
Are reversible steps regulated
- Reversible steps are not regulated
- But products may influence reaction rates (feedback regulation)
How does product affect reaction rate
When product conc gets too high it will feedback and reduce the activity of one of the enzymes further up the pathway.
What does Allosteric mean and what binds to it
A site other than where the substrate binds to (on an enzyme) - Activators and Inhibitors bind at this site
What are the two sites on a protein (enzyme)
- Catalytic site. Substrate(s) —-> Product(s)
- Regulatory site(s)
– Binding of specific regulatory molecule
– Affects catalytic activity
– can produce activation or inhibition
What is Phosphofructokinase
Phosphofructokinase is a kinase enzyme that phosphorylates fructose 6-phosphate in glycolysis.
What is a kinase enzyme
kinase, an enzyme that adds phosphate groups (PO43−) to other molecules.
What regulates Phosphofructokinase
Phosphofructokinase is regulated by allosteric regulators and by covalent modification (phosphorylation)
What are the Allosteric Regulations (muscle) of glycolysis
- What inhibits and Stimulates it
Inhibited by high ATP
Inhibited by high Citrate (a product further down the pathway)
Stimulated by high AMP
Stimulated by high F2,6,BP
What is the hormonal regulation (liver) of glycolysis
- What inhibits and Stimulates it
Stimulated by Insulin
Inhibited by Glucagon
What does HexoKinase do AND what
Hexokinase catalyzes the phosphorylation of glucose, the rate-limiting first step of glycolysis.
Hexokinase phosphorylates glucose thus it becomes charges meaning it cant travel out of cell
what happens when there is a high ratio of insulin to glucagon
There is a hormonal activation of phosphofructokinase
Why do some cells convert pyruvate to lactate?
when oxygen is limited, the body temporarily converts pyruvate into a substance called lactate, which allows glucose breakdown—and thus energy production
It also occurs when there is an inability to use NADH for
oxidative phosphorylation
What happens when all NAD+ is converted to NADH
glycolysis would stop when all NAD+ is converted to NADH
How is NAD+ generated
Normally, NAD+ is regenerated from NADH in stage 4 of metabolism
How many moles does NADH produce per mole of glucose
2 Moles of NADH
Why do some cells use Lactate Dehydrogenase (LDH)
- Some cells (e.g. RBC, eye lens) have no stage 3 or 4 of metabolism
- Stage 4 needs O2 - supply of O2 is sometimes insufficient (e.g. exercising skeletal muscles)
* Therefore, need to regenerate NAD+ by some other route
Lactate Dehydrogenase (LDH)
What is Lactate Dehydrogenase
LDH catalyzes the conversion of lactate to pyruvate and back, as it converts NAD⁺ to NADH and back.
Why is it important to recycle NAD/NADH
cells would run out of NAD+ and glycolysis would stop
Where is lactate produced and how much is produced WITHOUT MAJOR EXERCISE
40 - 50 g/24 hours
– RBC, skin, brain, skeletal muscle, G.I. tract
How much lactate is produced WITH MAJOR EXERCISE
What else changes
30 g/5 min
– Plasma levels increase 10-fold in 2 - 5 min
– Back to normal by 90 min
What else apart from exercise can affect lactate production
Pathological situations,
e.g. – SHOCK
– CONGESTIVE HEART DISEASE
Plasma concentration determined by relative rates of (3)
- production
- Utilisation
- Disposal
What is Hyperlactemia
- 2-5mM lactate measurement
- Below renal threshold
- No change in blood pH
(buffering capacity)
What is Lactic Acidosis
- above 5mM lactate measurement
- Above renal threshold
- Blood pH lowered
What is the normal lactate level
Concentration normally constant <1 mM
Where is fructose mostly metabolised
Liver
What is Essential fructosuria?
Essential fructosuria
- fructokinase missing
* Fructose in urine no clinical signs
What is Fructose intolerance
Fructose intolerance
- aldolase missing
* Fructose-1-P accumulates in the liver
- leads to liver damage and possible death
* Managed by removing fructose and sucrose from the diet
Where is lactose found
Lactose is a disaccharide found in milk
What is lactose metabolised into
galactose + glucose
Where does galactose metabolism occur
Metabolism in the liver (major tissue)
What is Galactosaemia
Galactosemia is a disorder that affects how the body processes a simple sugar called galactose.
What are the three enzymes involved in Galactosaemia
what is wrong with the enzyme
- Galactokinase
- UDP-galactose epimerase
- Uridyl transferase
Deficiency in any of these 3 enzymes can cause Galactosaemia
How rare Galactosaemia
1 in 30,000 births
What does Galactokinase do
The enzyme is responsible for the conversion of Galactose into Galactose-1P.
what does UDP - galactose epimerase do?
The enzyme is responsible for catalyzing the reversible conversion of galactose - 1P to UDP-galactose.
What does Uridyl transferase do?
facilitate change from galactose-1-P to glucose-1-P
What happens when you are unable to utilise galactose (2)
-Galactokinase deficiency (rare) - galactose accumulates
-Transferase deficiency (common) - galactose and galactose-1-P accumulate
What does the accumulation of galactose in tissues lead to
-Accumulation of galactose in tissues leads to its reduction to galactitol (aldehyde group reduced to alcohol group) by the activity of the enzyme aldose reductase:
-This reaction depletes some tissues of NADPH. In the eye the lens structure is damaged, (cross-linking of lens proteins by –S-S- bond formation) causing cataracts. In addition, there may be non-enzymatic glycosylation of the lens proteins because of the high concentration of galactose and this may contribute to cataract formation. The accumulation of galactose and galactitol in the eye may lead to raised intra-ocular pressure (glaucoma) which if untreated may cause blindness.
What does the accumulation of galactose 1-phosphate in tissues cause
Accumulation of galactose 1-phosphate in tissues causes damage to the liver, kidney and brain and may be related to the sequestration of Pi making it unavailable for ATP synthesis.
What is the treatment to Galactosemia
No lactose in diet
What is the pentose phosphate pathway
The pentose phosphate pathway is a metabolic pathway parallel to glycolysis.
It generates NADPH and pentoses as well as ribose 5-phosphate, a precursor for the synthesis of nucleotides. While the pentose phosphate pathway does involve the oxidation of glucose,
its primary role is anabolic rather than catabolic
Where does Pentose Phosphate Pathway start from
Starts from Glucose-6-phosphate
Why is the production of NADPH important
- Reducing power for biosynthesis
- Maintenance of GSH levels
- Detoxification reactions
What is the C5-sugar ribose used to sythenthise (2)
- Nucleotides,
- DNA & RNA.
what is the rate-limiting enzyme in the pentose sugar pathway
Glucose 6-phosphate dehydrogenase
Is ATP or CO2 produced in Pentose phosphate pathway
No ATP is synthesised. CO2 produced
What happens in Glucose-6-phosphate dehydrogenase (G6PDH) deficiency
-G6PDH is the rate limiting enzyme of the pentose phosphate pathway
-It supplies reducing energy by maintaining NADPH levels
- NADPH is required to protect against oxidative stress by maintaining the level of reduced glutathione.
- Since the pentose phosphate pathway is the only source of reduced glutathione in red blood cells, these are particularly affected by defects in the glucose-6-phosphate dehydrogenase enzyme.
-Patients with G6PDH deficiency are therefore at risk of haemolytic anaemia in states of oxidative stress such as infection or exposure to certain chemicals or medications. Damaged red cells are phagocytosed in the spleen and metabolism of the excessive haemoglobin to bilirubin can lead to jaundice.
What does pyruvate dehydrogenase in glucose metabolism do ?
Pyruvate does not enter stage 3 of catabolism directly but is first converted to acetyl~CoA by the enzyme pyruvate dehydrogenase
PDH is a multi-enzyme complex that catalyses the overall reaction: CH3COCOOH + CoA + NAD+ → CH3CO~CoA + CO2 + NADH + H+
