Metabolism 1/2 (handout p. 21-45) Flashcards Preview

FHB III- GI > Metabolism 1/2 (handout p. 21-45) > Flashcards

Flashcards in Metabolism 1/2 (handout p. 21-45) Deck (68):
1

Glucose, galactose and fructose (hexoses) play a central role in energy homeostasis in high
mammals. However, these molecules are unable to diffuse passively across cellular membranes, and
require transporter proteins for entry into and exit from cells. Describe the two distinct groups of transporters that
have been identified.

1.Hexose transporters down a concentration gradient (GLUT1, GLUT2, GLUT3, GLUT4
and GLUT5).

2. Hexose transporters against a concentration gradient using energy provided by an
electrochemical gradient of sodium, which is co-transported with the hexose (SGLT1,
SGLT2).

2

Describe the affinities of the transporters for glucose, galactose and fructose. Which have a high affinity for glucose (what value indicates this?) Which has a low affinity for glucose?

Class I (GLUTs 1-4) are glucose transporters.
Class II (GLUTs 5, 7, 9 and 11) are fructose transporters.
Class III (GLUTs 6, 8, 10 and 12) are structurally atypical members of the GLUT family, which are
poorly defined at present.

Each of the transporters has different affinities for glucose and the other hexoses, which largely
dictates their function. GLUT1, 3 and 4 have a high affinity for glucose (Km value = 2-5 mM, an
indicator of the affinity of the transporter protein for glucose molecules; a low Km value suggests a
high affinity), which indicates that they are functioning at maximal rate under physiologic
concentrations of glucose (approx. 5 mM). In contrast, GLUT2 has a low affinity for glucose (Km approx. 15
mM), which allows it to change transport rate in proportion to the increasing glucose concentrations
that occur after ingestion of a carbohydrate-rich meal.

3

How are GLUT transporters componsed. Describe the transport of glucose (saturable? direction? what drives it?).

In a resting post absorptive state, how is glucose metabolized?

GLUTs are composed of 12 membrane-spanning helices with an intracellular loop connecting the
6th and 7th helices. The facilitative transport of glucose is saturable, stereoselective and
bidirectional. Uptake of glucose by these transporters is along concentration gradient as intracellular glucose is actively metabolized by hexokinase and glucokinase. In resting post absorptive state about 70% glucose is metabolized in an insulin independent manner. This insulin-dependent and mostly independent mechanism is impaired in Type 2 Diabetes mellitus and in normoglycaemic subjects with family history of diabetes (glucose resistance).

4

Describe SGLT1.

What does it transport? What does it not transport? Where is it expressed?

Sodium glucose transporter 1; Co-transports one molecule of glucose or galactose along with two sodium ions. Does not transport fructose; Expressed in intestinal
mucosa, kidney tubules. It is insulin independent.

5

Describe SGLT2.

What does it transport? What does it not transport? Where is it expressed?

Sodium glucose transporter 2; Co-transports glucose and sodium ions. Does not
transport fructose or galactose; Expressed in kidney tubules.

6

Describe GLUT1.

What type of transporter? Where is it expressed?

Insulin independent plasma membrane transporter in RBCs (erythrocytes), brian and
endothelial cells. It is also widely distributed in fetal tissues

7

Describe GLUT2.

What type of transporter? Where is it expressed?

Insulin independent low affinity, high capacity transporter in the liver, also found in
the intestines and kidney (Bidirectional allowing glucose to flow in 2 directions).
Also, serves as a "glucose sensor" in pancreatic beta cells. GLUT 2 transports glucose
out of intestine, into the bloodstream, and into the liver. It is important to note that the
liver sees really high concentrations of glucose.

8

Describe GLUT3, GLUT4, GLUT5.

3- Insulin independent transporter in brain

4- INSULIN DEPENDENT transporter in MUSCLE, HEART and ADIPOCYTES.
Higher affinity for glucose. It gets glucose after we have eaten. This transporter is
not active during the fasting state.

5- Fructose transporter in skeletal muscle, adipose tissue, brian, sperm and erythrocytes

9

Which transporter is insulin independent low affinity, high capacity transporter in the liver, intestines and kidney?

GLUT2

10

The following describes which transporter:

INSULIN DEPENDENT transporter in MUSCLE, HEART and ADIPOCYTES.
Higher affinity for glucose.

GLUT4

11

Compare GLUT1 and GLUT 3 against GLUT2 and GLUT4 on a graph that compares glucose concentration to transport rate (% of Vmax).

Slide 32 or p 23

12

Glycolysis is regulated in three steps. Does it involve equilibrium or non-equilibrium
reactions? The enzymes that catalyze these steps are regulated in three
ways, describe.

Draw a chart w the steps.

non-equilibrium

allosterically, by covalent modifications, an regulation of the
amounts/synthesis of the enzymes.

flow chart p 24

13

Give an overview of glycolysis.

Partial breakdown of glucose into what? Describe the outputs.

What is produced?

Glycolysis is defined as a partial breakdown of glucose into 2 molecules of pyruvic acid, 4
protons and 4 electrons (accepted by 2NAD+ to form 2NADH + 2H+), and 2 net ATP (from
substrate-level phosphorylation). Note: it is important to know that the reaction actually goes
through twice resulting in the production of 4 ATP.

14

Where does glycolysis take place?

It produces energy in what form?

Glycolysis takes place in the cytoplasm, and, therefore, mitochondria are not required. It is
active in all cell types.

Glycolysis produces energy in the form of ATP and NADH.

15

Glycolysis is not isolated from other metabolic pathways.

Other molecules besides glucose can enter at a few points along the glycolytic pathway. Describe.

For example, the product of glycogen breakdown, glucose-6-phosphate, can enter the
glycolytic pathway at the second step. Glyceraldehyde-3-phosphate, which is produced by
photosynthesis, is also a glycolytic intermediate, so it can be directed from this anabolic
pathway into glycolysis when energy is needed.

16

Intermediates can be drawn out of the glycolytic pathway when energy levels are high, for use in biosynthetic pathways. What is an example?

during active energy
production pyruvate, the product of glycolysis, enters the citric acid cycle, but when energy
is not needed pyruvate serves as a substrate in amino acid synthesis.

17

At what point/step in glycolysis is glucose trapped in the cells?

Once glucose is phosphorylated into glucose 6-phosphate (in the first step of glycolysis), it is
trapped in the cells.

18

What enzyme mediates the most highly regulated part of glycolysis?

Aldolase A mediates the most highly regulated part of glycolysis (the splitting stage shown
below).

19

Describe the role of the following glycolytic enzymes.

Which use ATP and which generate ATP?


What does deficiency of glycolytic enzymes lead to?

1. Hexokinase/glucokinase – catalyzes the first reaction in glycolysis, which is the
phosphorylation of glucose into glucose 6-phosphate.
2. PFK-1 – is highly regulated and is important in locking in the glycolytic pathway.
3. Pyruvate Kinase

All the three enzymes mentioned above catalyze irreversible steps. It is important to note that the
first two enzymes (Hexokinase/glucokinase and PFK-1) utilize ATP, and the last two (Pyruvate
Kinase and Phosphoglycerate kinase) generate ATP.

The deficiency of glycolytic enzymes can lead to hemolytic anemia. Red blood cells burst, lose
hemoglobin, and you become anemic.

20

During what step does substrate level phosphorylation occur?

Substrate level phosphorylation occurs in the step when glyceraldehyde 3-phosphate is converted to 1,3-Bisphosphoglycerate and then 3-Bisphosphoglycerate by the enzyme Phosphoglycerate kinase.

21

Draw/explain the 3 stages of glycolysis.

P 26

22

What is allosteric regulation?

Reversible? Speed?

What effect might a buildup of the product have?

activation or inhibition of enzyme activity. The molecule or ligand
interacts with the enzyme at the active site and can either speed up the reaction or slow it
down. Allosteric regulation is reversible and is usually quick and transient. A buildup of
product can inhibit enzyme activity.

p27

23

Describe covalent modification and discuss the prime example.

Phosphorylation is initiated by a hormone and occurs when a phosphate group is
bonded with a hydroxyl group on the enzyme, adding a negative charge to the enzyme. The large negative charge initiates a conformational change, which then changes the activity of the enzyme. An example is the activation of protein kinase A (see picture below), which
phosphorylates syrine or threonine hydroxyl groups.

The phosphate is stuck on the hydroxyl group until it is removed by a phosphatase.
For example, insulin activates phosphatases to inhibit epinephrine and glucagon activity.

p 27, slide 39

24

For the following stimuli, what is the kinase?

hormone
neurotransmitter
cytokine
growth factor

See table on slide 40/ p 28

25

How are enyzmes synthesized?

Slide 42, p 28

This usually takes longer (can take many hours). A long-time fasting state or high consumption
of carbohydrates will initiate change in the enzyme activity.

26

Where is hexokinase present? Km?
How does it interact with glucose?

Hexokinase (a.k.a. Hexokinase Isozymes I, II and III):
- present in all cell types
- allosterically inhibited by its product, glucose
6-phosphate (e.g. feedback inhibition)
- constitutive enzyme, non-inducible, constant amount
low Km for glucose approx. 0.1 mM; saturated at low
glucose concentrations
- present at constant levels all the time, whether or not they
are activated.
- Hexokinase cannot handle very high levels of glucose.

27

Describe glucokinase. Where is it present?

What effect does fructose-6-phosphate have?

Km for glucose?

Glucokinase (a.k.a. Hexokinase Isozyme IV):
- present in liver and pancreas
- Translocation between nucleus (inactive) and cytosol (active)
- fructose 6-phosphate (downstream product) decreases activity by
promoting translocation to nucleus
- glucose increases activity by promoting
translocation to cytosol
- inducible enzyme; enzyme synthesis
induced by insulin — increased amount of
enzyme due to insulin
-Insulin increases expression of the gene.
- high Km for glucose ~ 7-10 mM;
not saturated at normal physiological
glucose concentration
-Glucokinase can handle large concentrations
of glucose in the liver.

Note: Blood glucose levels can get up to 5nM

28

On a graph, compare glucose concentration against relative enzyme activity.

(Graph lines for glucokinase and hexokinase).

Slide 49

p 29

29

Describe the allosteric regulation of hepatic phosphofructokinase-1 (PFK-1)

(What will provide positive regulation? Negative regulation?)

Slide 51
p 30

30

What is the major physiological activator of hepatic PFK-1? How is it formed? What catalyzes this reaction?

What inhibits its formation?

Fructose-2,6-bisphosphate is the major physiological activator of hepatic PFK-1 and is
formed from fructose-6-phosphate by a non-glycolytic step (refer to figure below).
- This is catalyzed by phosphofructokinase-2 (PFK-2).

Fructose-2,6-bisphosphate is formed when blood glucose (and insulin) are high (signaling
sufficient substrates for glycolysis); it is not formed when blood glucose is low (signaling
insufficient substrates for glycolysis).
- The formation of fructose-2,6-bisphosphate in the liver is inhibited by the hormones
glucagon and epinephrine. These hormones stimulate the formation of cAMP, which
activates protein kinase A (PKA).

slide 52, p 30

31

What does PFK-2 do?

What does it mean that it is a bifunctional enzyme? Describe its enzymatic activities.

- PFK-2 catalyzes the formation of fructose-2,6-bisphosphate and determines whether or not it
is made.
- PKA phosphorylates and inhibits PFK-2.

- PFK-2 is a bifunctional enzyme, a single protein with two enzyme activities.
- Makes fructose-2,6-bisphosphate and converts it back to fructose-6 phosphate.
- It cannot perform both functions of the enzyme.

PFK-2 has both a kinase domain and a phosphatase domain.
- The kinase domain catalyzes the formation of fructose-2,6-bisphosphate .
- The phosphatase domain catalyzes the reverse reaction, the formation of fructose-2,6-
phosphate.

32

How will glucagon and epinephrine in the liver affect enzymatic activity?

In the liver, only PFK-2 activity is inhibited by glucagon and epinephrine. Recall: these
hormones stimulate the formation of camp, which activates PKA, which then inhibits PFK-2.

In the liver, elevation of glucagon or epinephrine results in inhibition of the kinase domain of PFK-2; inhibition of the kinase domain blocks the formation of Fructose 2,6-bisPhosphate. Without Fructose 2,6-bisPhosphate, hepatic glycolysis is inhibited.

33

How will glucagon or epinephrine in the liver affect glycolysis? Why?

- In the liver, elevation of glucagon or epinephrine results in inhibition of the kinase domain of PFK-2; inhibition of the kinase domain blocks the formation of Fructose 2,6-bisPhosphate. Without Fructose 2,6-bisPhosphate, hepatic glycolysis is inhibited.
o Specifically, either glucagon or epinephrine can activate adenylyl cyclase to cAMP.
cAMP activates protein kinase A (PKA), which phosphorylates hepatic PFK-2 in the
kinase domain, leading to its inhibition.

34

How does high ATP and citrate affect the PFK-1 enzyme?

The PFK-1 enzyme is inhibited by high ATP and citrate.

ATP signals the presence of sufficient cytoplasmic ATP. In the absence of fructose-2,6-bisphosphate, cytosolic ATP is usually high enough to inhibit PFK-1.

35

The PFK-1 enzyme is inhibited by high ATP and citrate.

Describe citrate. Where is it formed?
What happens to citrate when ATP production by mitochondria is high?

Citrate, a CAC intermediate, is formed in the mitochondria. When ATP production
by mitochondria is high, the CAC enzyme isocitrate dehydrogenase is inhibited. This causes an accumulation of isocitrate and its precursor, citrate. As citrate accumulates,
some is transported to the cytoplasm, where it serves as a signal that there is sufficient cellular generation of ATP.

36

What are AMP and ADP? What do they do?

AMP and ADP are activators that are associated with low energy. They signal low
cytoplasmic ATP and a need for glycolysis to replenish ATP.

37

What happens if Fructose-2,6-bisphosphate is not present?

Fructose-2,6-bisphosphate is essential for enzyme activity. If it is not present, PFK-1 is inhibited under normal cellular conditions.

38

Glucagon and Epinephrine indirectly regulate hepatic PFK-1. Explain this.

- Recall how glucagon and epinephrine reduce fructose-2,6,-bisphosphate from the
previous section.

- In the absence of fructose-2,6-bisphosphate, physiological concentrations of ATP are able to inhibit PFK-1. Consequently, glucagon and epinephrine indirectly inhibit
hepatic PFK-1.

p32

39

Compare epinephrine affects glycolysis in liver vs heart. Explain.

Although Epinephrine Inhibits Hepatic Glycolysis, it Stimulates Glycolysis
in the Heart. Regulation of heart and skeletal muscle is very different from hepatic cells. For example, glycolysis is activated at the same step in both the heart and skeletal muscle. However,
there are no glucagon receptors in the heart and skeletal muscles.

In heart and skeletal muscle, epinephrine activates PFK-2 and glycolysis. This is due to the fact that PFK-2 has a different form in heart and skeletal muscle. In heart and skeletal muscle, PFK-2 lacks
the hydroxyl group in the kinase domain but has a hydroxyl group in the phosphatase domain. This
inhibits phosphatase activity and allows kinase activity. Epinephrine (but not glucagon) favors
formation of Fructose-2,6-bisphosphate, which goes on to activate glycolysis.

40

Describe the regulation of pyruvate kinase by allosteric modification and covalent mechanisms.

When does pyruvate kinase act?

How is it activated?

How is PK inhibited?

How do glucagon and epinephrine act to affect pyruvate kinase?

What removes the phosphate?

What can a genetic deficiency of pyruvate kinase lead to?

- Pyruvate kinase acts at the final place where ATP is synthesized.
- It is activated by fructose-1,6-bisphosphate, which feeds the forward reaction.
- PK is inhibited by ATP and alanine.
- Alanine is an amino acid that increases in fasting mode.
- Alanine serves as a significant precursor for gluconeogenesis.
- Glucagon & Epinephrine act via cAMP and protein kinase A to cause the phosphorylation
and inactivation of hepatic pyruvate kinase.
- Phosphoprotein phosphatase removes the phosphate.
- A genetic deficiency of pyruvate kinase can lead to hemolytic anemia.

41

Draw a summary of allosteric regulation of the glycolytic pathway.

Slide 63/ p 35

42

Glucagon (and epinephrine) inhibits hepatic glycolysis by direct and indirect mechanisms
involving covalent modification (phosphorylation) of enzymes.

Describe how/when glucagon is synthesized. Where does it act?

Describe epinephrine. From where is it released? Where does it act?

The hormone GLUCAGON is synthesized and secreted by pancreatic alpha cells in times of low
blood glucose. Because glucagon receptors are present in the liver (but not in skeletal muscle or
heart) and because glucagon is metabolized by the liver, its actions are limited to the liver.

EPINEPHRINE is released from the adrenal medulla. Because there are receptors for epinephrine/adrenaline on hepatocytes, skeletal and heart muscle, and adipose tissue, its actions are
not limited to the liver. Inhibition of hepatic glycolysis preserves glucose for utilization by tissues,
which have a fuel preference or high demand for glucose.

43

Glucagon (or epinephrine) regulates hepatic glycolysis via covalent modification (phosphorylation)
at two enzymatic steps. Describe.

PFK-1 (via inhibition of PFK-2) and pyruvate kinase.

44

What will be the effect of inhibition of PFK-2?

Inhibition of PFK-2
leads to decreased synthesis of fructose 2,6-bisphosphate, the major allosteric activator of PFK-1.
The decline in fructose-2,6-bisphosphate results in a decrease in PFK-1 activity.

Thus, glucagon
(and epinephrine) inhibit hepatic glycolysis by indirectly inhibiting PFK-1 and by directly inhibiting pyruvate kinase

45

How do glucagon and epinephrine inhibit glycolysis? (2 ways)

Describe their effect in the liver.

In the liver, glucagon and epinephrine also decrease the synthesis of the three irreversible enzymes of glycolysis.

46

Increased insulin or decreased cAMP (low glucagon,
low epinephrine) result in . .

Increased synthesis of the following enzymes.
Glucokinase
Pyruvate kinase-1
Phosphofructokinase

47

Glycolysis plays an important role in energy metabolism in nearly
every living tissue; it can function under aerobic and anaerobic
conditions. Draw.

p 37
slide 67

NAD/NADH are in limited supply in the cytoplasm, and NAD+ must be regenerated for glycolysis to
continue

48

When is NADH oxidized?

NADH is oxidized when pyruvate is converted to lactate.

NAD/NADH are in limited supply in the cytoplasm, and NAD+ must be regenerated for glycolysis to
continue

49

How can cytoplasmic NAD+ be regenerated?

Alternatively, cytoplasmic NAD+ can be regenerated by using mitochondria-linked shuttles (e.g., the
glycerolphosphate and malate aspartate shuttles). In these shuttles, reducing equivalents are
transferred to the mitochondria. Mitochondrial FADH2 or NADH are formed as a result of this
transfer. Since mitochondrial FADH2 or NADH can be reoxidized using the electron transport
chain, far more ATP can be formed via this route than through generation of lactate.

50

Describe what happens in mitochondria-linked shuttles.

Alternatively, cytoplasmic NAD+ can be regenerated by using mitochondria-linked shuttles (e.g., the
glycerolphosphate and malate aspartate shuttles). In these shuttles, reducing equivalents are
transferred to the mitochondria. Mitochondrial FADH2 or NADH are formed as a result of this
transfer. Since mitochondrial FADH2 or NADH can be reoxidized using the electron transport
chain, far more ATP can be formed via this route than through generation of lactate.

51

Describe lactate dehydrogenase. Where is it present? What happens if you lyse or damage cells?

Is it basic or acidic?

LDH is present in all the cells. If you lyse or damage the cells, LDH goes up.
LDH does a better job of taking pyruvate to –L-lactate rather than the other way around.
L-lactate is an acidic molecule. If it stays in the cell it can decrease the pH and disrupt pHsensitive
processes. Buffering usually takes care of this, but too much lactate can lead to acidosis.

p 38

52

Describe LDH isozymes.

M4
H4

In skeletal muscle, the M4 isozyme “prefers” to catalyze the conversion of pyruvate to lactate;
this allows for high bursts of energy.

In heart muscle, the H4 isozyme prefers to catalyze the conversion of lactate to pyruvate; this
allows for a sustained production of energy. Pyruvate is then decarboxylated into acetyl-CoA
and entered into the citric acid cycle.

53

What is the normal serum concentration of lactate to pyruvate?

10/1

54

What catalyzes the conversion of pyruvate to acetyl-CoA?

Pyruvate Dehydrogenase (PDH) Is a Multienzyme Complex (E1,E2,E3)
That Catalyzes the Conversion of Pyruvate to Acetyl-CoA.

E1 has pyruvate dehydrogenase activity and uses thiamine pirophosphate.
E2 has dihydrolipoyl transacetylase
E3 – dihydrolipoyl dehydrogenase

55

Pyruvate Is Oxidatively Decarboxylated by the Pyruvate Dehydrogenase
(PDH) Enzyme Complex. Describe.

What does a deficiency in PDH lead to?

Pyruvate (3C) is decarboxylated immediately. The remaining two carbons are added to
thiamine pyrophosphate. Thiamine pyrophosphate donates the acetyl group to a lipoic acid
derivative, dihydrolipoyl transacetylase. Lipoic acid is alternated between an oxidized for and
reduced form. For it to be able to shuffle between those forms, it is necessary to have the third
enzyme activity.

A deficiency in PDH leads to an inability to make acetyl CoA, which then impairs the ability of
tissue to function and survive. The main tissues that are affects are the brain (which is completely
glycolytic), as well as the heart.

56

What does poisoning with arsenic do?

Poisoning with arsenic inhibits the shuttling of the lipoic acid in the oxidized and reduced form. The
symptoms would mimic those of someone who has a pyruvate dehydrogenase deficiency. As a
result, pyruvate and lactate accumulates in the bloods and causes lactic acidosis.

57

How is PDH inhibited?

PDH is not inhibited by glucagon and epinephrine, but it is inhibited by the products through
allosteric regulation. A kinase can also be activated that will phosphorylate and inhibit the enzyme.
Factors that inhibit the kinase activate the PDH.

58

Describe the mechanism of the pyruvate dehydrogenase reaction; the pyruvate dehydrogenase multienzyme
complex. Give equation.

Slide 77
p 39,40

59

Accumulation of the End-Products of the Reaction Catalyzed by PDH Inhibit the Enzyme by
Two Mechanisms:

Describe.

A. The end-products of the PDH reaction allosterically inhibit PDH.

B. The end-products of the PDH reaction cause PDH to become phosphorylated;
phosphorylation of PDH inhibits it activity.

p 41, slide 79, 80

60

PYRUVATE DEHYDROGENASE (PDH) COMPLEX: VITAMIN REQUIREMENT TO BE
ACTIVE.

What vitamin is required for PDH-E1 to be active?

E2?

E3?

Slide 82

p 42

E1- thiamine/ B1
E2- pantothenate/ B5
E3- riboflavin/B2, niacin/B3

61

What do anaerobic conditions favor the formation of?

Anaerobic Conditions Favor the Formation of Lactate

slide 86

62

What does the metabolism of glucose yield?

What does metabolism of glucose through glycolysis and citric acid cycle yield?

Metabolism of glucose ---> 2 lactate yields a net of 2 ATP.

Metabolism of glucose through glycolysis and the citric acid cycle yields a net production of approx 32 ATP.

63

What must happen before galatose and fructose can be metabolized?

The Metabolism of Galactose and Fructose Requires Distinct Enzymes

Slide # 87

In order for dietary galactose (a component of lactose) and fructose (a component of sucrose) to be
metabolized, they must first be converted to a glycolytic intermediate.

64

There are genetic disorders which cause a deficiency of one of the key enzymes involved with
the conversion of galactose and fructose to glycolytic intermediates.

Describe galactosemia.
What are clinical symptoms? How is it treated

is a genetic disorder caused by a deficiency of either galactokinase or
galactose 1-phosphate uridyltransferase. Accumulation of galactose facilitates increased activity of a normally minor pathway, i.e. formation of galactitol.

Slide 88-92, p 43

65

What does HEREDITARY FRUCTOSE INTOLERANCE result from?

results from a genetic deficiency (recessive) of
aldolase B.

66

Where is fructose found? What must happen before it can be ingested via glycolysis?

What happens next?

Fructose is a monosaccharide that is found in fruit and honey. It is also part of the disaccharide
sucrose. In order for ingested fructose to be utilized via glycolysis, it must first be converted to
fructose 1-P. Fructose 1-Phosphate is then cleaved by Aldolase B into glyceraldehydes and
dihydroxyaceteone phosphate (DHAP). DHAP is a glycolytic intermediate.

Ingested fructose is rapidly converted to fructose 1-phosphate; this reaction utilizes ATP. Because
the defective aldolase B cannot cleave fructose 1-P, this leads to intracellular trapping of fructose 1-
P. Thus, consumption of fructose results in accumulation of fructose 1-phosphate and depletion
of Pi and ATP. When Pi is tied up as fructose 1-phosphate it is impossible to generate ATP; ATP
levels fall quickly. Cells are damaged because they cannot maintain normal ion gradients through
ATP-dependent pumps. Phosphorylated sugars are toxic to the cell.

67

What are symptoms and treatment of HEREDITARY FRUCTOSE INTOLERANCE?

Hypoglycemia, Vomiting, Jaundice and Hepatic failure/cirrhosis

Treatment of Hereditary Fructose Intolerance
Rapid detection
Removal of dietary sucrose and fructose

slide 45

68

What is essential fructosuria?

ESSENTIAL FRUCTOSURIA
Defect in fructokinase; Fructose detected in blood and urine; Benign, asymptomatic condition.