Carbohydrates + Glycolysis

Question 1

Describe a primary lactase deficiency

Answer 1

• Absence of lactase persistence allele meaning lactase enzyme is no longer expressed (only expressed during early childhood)
• Only occurs in adults

Question 2

Describe secondary lactase deficiency

Answer 2

• caused by injury to S.intestine ie gastroenteritis, coeliac disease, crohn’s disease, ulcerative colitis
• occurs in both infants and adults
• generally reversible

Question 3

Describe congenital lactase deficiency

Answer 3

• extremely rare

- autosomal recessive defect in lactase gene therefore cannot digest milk

Question 4

What symptoms might someone experience if they have a lactose intolerance?

Answer 4

• bloating and cramps
• flatulence
• diarrhoea
• vomiting
• rumbling stomach

Question 5

How are monosaccharides absorped?

Answer 5

They are actively transported into the intestinal epithelial cells by sodium-dependent glucose transporter 1 (SGLT1) and then into the blood via GLUT2

Question 6

How does a SGLT1 work?

Answer 6

It co-transports (symports) 2 sodium molecules with a glucose/galactose into intestinal epithelial cells from the gut lumen

Question 7

There are 5 GLUT proteins that move monosaccharides tissue form the blood, by what mechanism is this done?

Answer 7

Facilitated diffusion

Question 8

Name some cell types that have an absolute requirement for glucose, why can they not metabolise other molecules? (4)

Answer 8

Red blood cells- no mitochondria therefore can only perform glycolysis

Neutrophils- have mitochondria but mainly used for the production of free radicals which it uses to destroy bacteria therefore can only perform glycolysis

Innermost cells of kidney medulla- high energy demand but little oxygen supply

Lens of eye- no capillaries and blood in lens of eye therefore little oxygen (cannot do oxidative phosphorylation) so can only perform glycolysis. (Gets oxygen form diffusion through air)

Question 9

What are the 3 important enzymes involved in glycolysis?

Answer 9

Hexokinase (glucokinase in liver)

Phosphofructokinase-1

Pyruvate kinase

Question 10

Why is glucokinase used in the liver during glycolysis and not hexokinase?

Answer 10

Hexokinase has a lower affinity for glucose than glucokinase and glucokinase is not inhibited by a high conc of glucose

Question 11

What is the clinical relevance of glycolysis in relation to cancer?

Answer 11

The rate of glycolysis in cancer is up to 200 times greater, which means you can measure the uptake of FDG (a radioactive modified hexokinase substrate) using positron emission tomography to locate cancers

Question 12

What is the role of PFK in glycolysis?

Answer 12

Converts fructose-6-phosphate into fructose-1,2-bisphosphate, using an ATP

Question 13

How and where is PFK regulated?

Answer 13

Allosteric regulation in muscle

Hormonal regulation in the liver

Question 14

What two molecules inhibit PFK in glycolysis when they’re at high concentrations and where are they found?

Answer 14

High ATP in muscles (allosteric regulation)

High glucagon in liver (hormonal regulations)

Question 15

What two molecules stimulate PFK in glycolysis when they’re at high concentrations and where are they found?

Answer 15

High AMP in muscle (allosteric regulation)

High insulin in the liver (hormonal regulation)

Question 16

What are high energy level signals in glycolysis and what do they do?

Answer 16

High [NADH] or low {
[NAD+]

Causes inhibition of step 6

Inhibits glycolysis

Question 17

What is the enzyme involved in the final step of glycolysis?

Answer 17

Pyruvate kinase

Produces pyruvate

Question 18

What is pyruvate kinase stimulated by?

Answer 18

A high insulin:glucagon ration (ie low insulin, high glucagon)

Question 19

What is insulin often referred to as?

Answer 19

The hormone of plenty

Question 20

What can 1,3- bisphosphpglycerate (produced during step 6 of glycolysis) be converted into, what does it go on to do and what enzyme completes the reaction?

Answer 20

2,3-bisphosphoglycerate (2,3-BPG)

Modulates the affinity of Haemoglobin for oxygen (promotes release), produced in RBC

Enzyme: bisphosphoglycerate mutase

Question 21

DHAP is a molecule produced during reaction 4 of glycolysis, it can be converted to glyceraldehyde 3-P giving two 3 carbon molecules (which will eventually give 2x pyruvates). However, using NADH it can be converted into something else. What is the molecule and the enzyme that completes this step. What does the molecule produced go on to become?

Answer 21

DHAP–>glycerol phosphate

Enzyme: glycerol 3-phosphate dehydrogenase

Glycerol phosphate is essentially the back bone of glycerol, it combines with fatty acids to produce triacylglycerol
(Produced in adipose and liver, lipid synthesis in adipose requires glycolysis but the liver can phosphorylate glycerol directly, therefore is not dependant on glycolysis)

Question 22

How many molecules of NADH are produced per mole of glucose?

Answer 22

2

Question 23

What does step 6 of glycolysis require?

Answer 23

NAD+ molecules

Question 24

When would you need to regenerate NAD+ by Lactate dehydrogenase (LDH) route?

Answer 24

Where there is no oxygen or no stage 4 metabolism

Ie in RBC (no mitochondria) or muscles and gut (where O2 is often reduced)

Question 25

What is the plasma lactate conc determined by? (3)

Answer 25

Production, utilisation (liver, heart and muscles) and disposal (kidneys)

Question 26

What is a slightly raised plasma lactate called? Does this effect the blood pH?

Answer 26

Hyperlactaemia (2-5mM)
Below renal threshold therefore no change in blood pH as kidneys are able to excrete and deal with the raised lactate levels

Question 27

What is the normal plasma lactate levels?

Answer 27

Less than 1mM

Question 28

What is a plasma level over 5mM called? Why is this bad?

Answer 28

Lactic acidosis

Above renal threshold so kidneys cannot maintain blood pH and it is subsequently lowered.

It is often a Christi all marker in the acutely unwell patients.

Question 29

Lactose is a disaccharide found in milk, what is it made of?

Answer 29

Glucose and galactose.

Question 30

What is galactosaemia?

Answer 30

A deficiency in any the following enzymes-
galactokinase
Uridyl transferase
UDP- galactose epimerase

Question 31

What is essential fructosuria?

Answer 31

Fructokinase missing in fructose metabolism pathway

There are no clinical signs except for fructose in urine

Question 32

What is fructose intolerance?

Answer 32

The absence of aldolase in the fructose metabolism pathway

Fructose-1-P accumulates in liver which can lead to liver damage

Treatment is often to remove fructose from diet.

Question 33

What does the penthouse phosphate pathway start with?

Answer 33

Glucose 6 phosphate

Question 34

What is an important product of the pentose phosphate pathway and what can it be used for?

Answer 34

NADPH

• reducing power for biosynthesis
• maintained of GSH levels
• detoxification reactions

Question 35

What is the product at the end of the pentose phosphate pathway and what is it required for?

Answer 35

C5 sugar ribose

• nucleotides
• DNA
• RNA

Question 36

Is the pentose phopshat pathway energy providing?

Answer 36

Not directly because there is no ATP produced

There is CO2 produced though

Question 37

What is the rate limiting enzyme of the pentose phosphate pathway?

Answer 37

Glucose 6-phosphate dehydrogenase

Question 38

What is the key regulator of glycolysis?

Answer 38

PFK

Question 39

What is the action of PFK (phosphofructokinase)?

Answer 39

Fructose-6-phosphate to fructose 1,6-bisphosphate