Glucose Metabolism 1

Question 1

describe dietary intake of glucose and where carb digestion happens

Answer 1

In Western society about 50% of our diet is composed of carbohydrates
60% of this comes from starch, 30% from sucrose, and 10% from lactose
Although carbohydrate breakdown begins as soon as food enters the mouth (salivary amylase) the majority of carbohydrate digestion takes place in the small intestine

Question 2

describe chemical characterisation of carbohydrates

Answer 2

• Polysaccharides: chains of saccharide molecules- starch
• Disaccharides: two saccharide units- sucrose (glucose + fructose), lactose (galactose + glucose), and maltose (glucose + glucose)
• Monosaccharide: singlesaccharide-
glucose, fructose, galactose

Question 3

When do carbohydrates become glucose

Answer 3

By the time dietary carbohydrate leaves the small intestine all di- and polysaccharides have been converted to their constituent monosaccharides.
These are then transported to the liver which has a central role in the storage and transport of all the bodies energy sources including glucose.

Question 4

Why is Glucose important?

4 reasons

Answer 4

1. It is the first choice energy substrate used by all body tissues, used in preference to all other fuel sources such as fatty acids.
2. It the only fuel source capable of producing energy in the absence of oxygen which is important in blood cells/skeletal muscle during exercise (anaerobic glycolysis)
3. Brain and nervous tissues have an absolute requirement for glucose (without it neurons die)
4. Red blood cells use glucose exclusively as an energy source.

Question 5

It is essential that blood glucose levels remain stable in all physiological situations, homeostatic regulation is therefore vital.
How are blood glucose levels controlled during fed state?

Answer 5

Glucose levels rise.
Hormones are released (particularly insulin).
Increased glucose taken up into tissues.
Glucose broken down to produce energy by glycolysis. Excess glucose stored as glycogen. Blood glucose levels rapidly return to pre-prandial levels (2h).

Question 6

It is essential that blood glucose levels remain stable in all physiological situations, homeostatic regulation is therefore vital.
How are blood glucose levels controlled during fasting state?

Answer 6

Glycogen stores in the liver converted to glucose by glycogenolysis (12-24h). Once depleted (>24h) glucose can be produced from non- carbohydrate sources such as pyruvate, lactate, glycerol and amino acids by glucenogenesis.

Question 7

It is essential that blood glucose levels remain stable in all physiological situations, homeostatic regulation is therefore vital.
How are blood glucose levels controlled during extreme carbohydrate dehydration

Answer 7

Increased breakdown of fats into ketones occurs.

Protein breakdown.

Question 8

Glucose in the body has 3 main fates- what are they?

Answer 8

1. Most will be transported in the blood to peripheral tissue, particularly the brain, muscle and kidney where it will undergo glycolysis ultimately producing energy in the form of ATP.
2. Glucose which is surplus to immediate requirement will be converted to glycogen in the liver and skeletal muscle. This glycogen is used by the body to maintain a constant blood glucose level between meals and during extreme exercise.
3. When glycogen reserves are saturated glucose will be converted to fatty acids for long term storage as triglycerides.

Question 9

what is glycolysis

Answer 9

Glycolysis is a major energy production pathway and takes place in the cytoplasm of cells.
Glycolysis is the first pathway of glucose catabolism which converts the 6 carbon glucose molecule into 2x 3 carbon pyruvate molecules.
2 of the high energy compounds, ATP and NADH are produced in this pathway.

Question 10

what is the pathway of glucose in anaerobic glycolysis and aerobic glycolysis?

Answer 10

a) Anaerobic glycolysis (no requirement for oxygen):
Glucose 2x pyruvate 2x lactate

b) Aerobic Glycolysis (requires oxygen):
Glucose 2x pyruvate 2xacetyl CoA (Krebs cycle)

Question 11

Glycolysis is composed of 2 stages- describe them

Answer 11

Stage 1: A chemical priming stage requiring energy in the form of 2xATP: Glucose Fructose 1,6 Bisphosphate (when [phosphate is added it stops the glucose leaving the cell which allows it to be further metabolized)

Stage 2: An energy yielding stage which produces 4xATP and 2xNADH
Fructose 1,6 Bisphosphate 2xPyruvate

Question 12

why is the phosphorylation of glucose is important in glycolysis

Answer 12

Important for 2 reasons:

1. The phosphorylated form of glucose is no longer free to move across the membrane of cells and becomes trapped in the cytoplasm of the cell where glycolysis takes place.
2. The phosphorylated glucose is now primed for further breakdown.

Question 13

Control of Glycolysis – how is glucose phosphorylated?

Answer 13

The phosphorylation of glucose can be catalysed by two enzymes:
• Hexokinase - present in all cells
• Glucokinase - present in the liver and pancreas.

Hexokinase is good at phosphorylating glucose when its concentration is low.
Glucokinase is only able to phosphorylate glucose when its concentration is high

Question 14

Glucokinase is active only at high concentrations of glucose- what 2 times is this important

Answer 14

1. When glucose levels are high e.g. post prandial glucokinase is active and the liver can trap and store glucose
2. When glucose levels are low, eg fasting, glucokinase is no longer active and the glucose available is used tissues such as the brain which are critically dependent on glucose.

Question 15

what is the Importance of Phosphofructose Kinase in control of glycolysis

Answer 15

A key enzyme in regulating glycolysis is phosphofructokinase (PFK)
PFK is regulated by the energy levels in the cell (more active when ATP levels are low)
PFK is also regulated by citrate. High citrate levels in the cell indicate abundant levels of building blocks for biosynthesis and this inhibits PFK.
This allows the Krebs Cycle (Citric Acid Cycle) and glycolysis to talk to each other. PFK is most active when both energy and citrate are low.

Question 16

describe the reactions in anaerobic glycolysis and where this happens

Answer 16

In anaerobic conditions pyruvate is converted to lactate by lactate dehydrogenase.
This reaction also allows the oxidisation of NADH (produced during the breakdown of glucose to pyruvate) to NAD+. Without this glycolysis will stop.
This takes place in exercising muscle (lack of O2) and red blood cells (which don’t have mitochondria). It is 100xs faster than aerobic glycolysis but it is inefficient as it produces only 2xATP for every glucose molecule.

Question 17

describe the reactions in aerobic glycolysis and where this happens

Answer 17

Aerobic glycolysis requires both oxygen and mitochondria
In the mitochondria, pyruvate is oxidised to Acetyl CoA and this eventually to CO2 via the krebs cycle and oxidative phosphorylation (electron transport chain). NADH is also oxidised to NAD+ .
This process is much more efficient at producing energy than anaerobic glycolysis producing 36-38 ATPs for every glucose molecule.

Question 18

summarise glycolysis

Answer 18

The breakdown of 6-carbon glucose to produce 2x 3- carbon pyruvate molecules, and a total of 2xATP and 2xNADH.

Takes place in the cytoplasm

2 main stages:

i. requires energy in chemical priming, glucose to fructose 1,6 bisphosphate
ii. energy yielding, production of pyruvate

Progresses aerobically –conversion to acetyl CoA and entry to the TCA (krebs) cycle- (efficient) or anaerobically - pyruvate converted to lactate -(fast)

Glycolysis is a series of enzyme steps with the main regulatory enzymes being: hexokinase/glucokinase and phosphofructokinase

Question 19

What is glycogen?

Answer 19

Glycogen is a large, branched polymer of glucose.

The glucose molecules are linked together forming linear chains and branches.

Question 20

Where is glycogen stored?

Answer 20

There are 2 major sites of glycogen storage in the body:

1. Liver – contains the only glycogen store which is available to release glucose into the blood and supply this to other tissues
2. Skeletal muscle – produces glycogen stores purely for use within muscle as glycogen here is not converted into glucose as skeletal muscle cells lack glucose 6 phosphatase.

Question 21

why is glycogen storage important

Answer 21

Glycogen storage is important to:

• Regulate blood-glucose levels.
• Provide a reservoir of glucose for use between meals and strenuous muscle activity

Question 22

How is glycogen synthesised

Answer 22

Glycogen synthesis is adding glucose molecules to glycogen:
1. The conversion of glucose to glucose-6-phosphate glucokinase

2. Glucose-6- phosphate is converted to glucose-1- phosphate
3. Glucose-1- phosphate is converted to UDP-glucose which can bind to other UDP-glucose molecules
4. The build up of the glycogen polymer.

Glycogen sythesis is catalysed by an enzyme called glycogen synthase.
Regulation of glycogen synthase prevents synthesis and breakdown of glycogen happening concurrently.

Question 23

How is glycogen broken down?

Answer 23

The process by which glycogen is broken down is called glycogenolysis
It is composed of 3 main steps:
1. The breakdown of the glycogen polymer.
2. The production of glucose-1-phosphate from glycogen.
3. The conversion of glucose-1-phosphate to glucose-6-phosphate to allow further metabolism.

Question 24

what does glycogen phosphorylase do in glycogenolysis

Answer 24

Glucose units are released from glycogen by the action of glycogen phosphorylase
This step does not use ATP so is energy efficient and produces a phosphorylated form of glucose…
Glycogen phosphorylase regulates glycogenolysis so that synthesis and breakdown of glycogen do not occur at the same time.

Question 25

How are the synthesis and degradation of glycogen regulated?

Answer 25

These must be regulated so that degradation and synthesis does not take place at the same time
The synthesis and degradation of glycogen are controlled by different pathways.
The key enzyme in regulation of synthesis isGglylycocgoegnesny,nthase in degradation it is Glycogen phosphorylase.
When glycogen synthase is fully active, phosphorylase is almost completely inactive.

Question 26

Phosphorylase is the enzyme responsible for controlling the breakdown of glycogen. Under what conditions would you expect it to be active?

Answer 26

1. Low ATP levels

2. Low glucose-6-phosphate levels

Question 27

Synthase is the enzyme responsible for controlling the synthesis of glycogen. Under what conditions would you expect it to be active?

Answer 27

1. High ATP

2. High glucose-6-phosphate levels

Question 28

give a summary of processes involved in glycogen metabolism

Answer 28

• Glycogen is a polymer of glucose molecules
• It is broken down (glycogenolysis) when
• ATP and/or blood glucose levels are low
• It is synthesised when ATP levels are high and/or blood glucose levels are high.
• Glycogen synthase and phosphorylase regulate these processes so that they can not occur simultaneously

Question 29

describe glycogen storage disease (GSD)

Answer 29

As glycogen molecules are quite large an inability to degrade them can cause cells to become enlarged. It also results in a loss of functional ability to use glycogen as an energy source and also a blood-glucose buffer.
Glycogen storage diseases occur in patients with genetic deficiencies in enzymes controlling glycogen metabolism.
Seven types of GSDs have been described but these are rare

Question 30

Type I (von Gierkes) was the first glycogen storage disease- describe it

Answer 30

it is the most common.
It is caused by a deficiency in glucose-6-phosphatase
Patients unable to release glucose from glycogen due to the deficiency of glucose-6- phosphatase and hence with time glycogen builds up in the liver.
Clinical symptoms:
• massive enlargement
• growth retardation
• fasting hypoglycemia of liver
• increased lactic acid concentrations in the blood (due • to excessive glycolysis)
• hyperuricemia and hypertriglyceridemia

Question 31

what is Synthesis of Glucose and where does it occur?

Answer 31

What: the conversion of non-carbohydrate molecules into glucose

Where: Mainly in the liver (90%), some in the kidney under certain conditions

Question 32

why do we need synthesis of glucose

Answer 32

• To maintain blood glucose levels when supplies of glucose and glycogen have been exhausted i.e. After fasting for periods of more than 1 day (including starvation) or during periods of intense exercise.
• To ensure that the brain, RBC and muscle have enough glucose to meet their metabolic demands

Question 33

how is there glucose synthesis

Answer 33

• Gluconeogenesis converts pyruvate into glucose
• Non-carbohydrate sources are first converted to pyruvate
• Major non-carbohydrate sources are: 
o Lactate – from skeletal muscle
o Amino acids –from dietary protein or breakdown of skeletal muscle protein during starvation 
o Glycerol – from fat in adipose tissue

Question 34

describe the conversion of lactate into glucose (‘The Cori Cycle’)

Answer 34

During anaerobic glycolysis pyruvate is converted into lactate:
• Provides a source of NAD+ to drive glycolysis
• Lactate is released back into the blood stream, travels to the liver and is converted back to glucose
• This is then returned to the muscle for energy and to replenish glycogen stores

Question 35

describe the conversion of fat into glucose

Answer 35

Glycerol backbone of lipids can be used for gluconeogenesis

Glycerol is exported from the adipocyte tissue to the liver where it gets converted to glucose

Question 36

describe the conversion of amino acids into glucose ‘The Alanine Cycle’

Answer 36

Alanine is a product of amino acid breakdown in the muscle
The alanine/glucose cycle describes the transport of alanine from the muscle to the liver, subsequent conversion to pyruvate and then glucose and transport back to the muscle.
As muscle must remove toxic urea the export of alanine via this cycle provides a useful tool.

Question 37

How is gluconeogenesis regulated

Answer 37

2 of the novel enzyme steps in gluconeogenesis provide regulation to the process:

1) Frucose-1,6-biphosphatase which catalyses the reaction fructose-1,6-bisphosphate fructose-6-phosphate
2) Glucose-6-phosphatase which catalyses the reaction glucose-6-phosphate glucose

As in glycogen synthesis and breakdown, glycolysis and gluconeogenesis must be regulated to avoid both occurring at the same time