P.

09 CARBOHYDRATES OF PHYSIOLOGIC  Fructose undergo glycolysis only when glucose is not

SIGNIFICANCE (PART 4) enough, increased load of both fructose and glucose will
Dr. Salango | Feb 6, 2018 favor formation of fatty acid
 Galactose is converted to glucose only if glucose is not
sufficient. Too much galactosetowards glycogenesis
OUTLINE
 Glucose will only undergo glycolysis.
I. Hexose Metabolism
II. Monosaccharide Storage and Phosphorylation
III. Hepatic Glucose Transport
IV. Hepatic Glucose and Fructose Metabolism II. MONOSACCHARIDES STORAGE AND
A. After a meal PHOSPHORYLATION
B. Between meals
C. After sugar consumption
V. Recall on Fructose, Glucose Metabolism
VI. Negative Feedback Inhibition
VII. Fructose and Mannose Metabolism
VIII. Fructose Intake
IX. Fructose Metabolism

I. HEXOSE METABOLISM

 After passing through the small intestines,

monosaccharides will then be transported towards the
capillaries or to the lacteals for transport into the blood
stream
 Once in the blood stream, monosaccharides will be
deposited into the skeletal muscle
 Skeletal muscle is the preferred destination of
glucose and stores glucose for itself alone
 Glucose will be transported to other sites such as
the liver, when skeletal muscles reach maximal
 The priority of hexose metabolism is glycogen
storage capacity
 Fat follows if there is no space for glycogen. This is
 If not physically activeless space for
because it is easier to drive fuel from glycogen than fat.
glycogen convert to glycerolfatty acid
 Awell-trained athlete vs a beginner, the beginner is
fat deposition
not expected to consume much glycogen compared
 storage capacity
to the trained athlete, Even with same intensity of
- greater storage per cell: hepatocyte
training.
- as a whole: most of the glycogen is stored
 Larger muscles consume more energy, if you build
in the skeletal muscles
up your muscle; you actually consume more fuel
 There is entry of glycogen, starch, disaccharides, and
while resting, in order to consume more, have to be
hexoses into the preparatory stage of glycolysis.
more active.
 Phosphorylation reaction traps them inside the cell
 Glyceraldehyde  Proceed to synthesis of
 Non-specific enzyme: Hexokinase (liver)
(Triglyceride/TAG), glyceraldehyde conversion to
 Specific components (depend on cell type): glucokinase
glycerol which is the backbone for TAG
(skeletal muscles), fructokinase, galactokinase
 More fructose = fatter, prefers the pathway that leads
to glycerol formation.

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  Hexokinase
o is found in all organs especially the skeletal
muscles
o not specific for glucose, can also phosphorylate
mannose to mannose-6-phosphate.
 No glucose transporter: SPERM CELLS.

III. HEPATIC GLUCOSE TRANSPORT

1. Hepatocytes
 Stores glucose but releases it if needed in
other organs
 Bidirectional glucose transport
 Maintains steady glucose state (80-100 mg/dL)
according to Doc Salango(80-120 mg/dL)
 Feeding state: glucose goes inside the cell
 Fasting state: glucose goes outside the cell

2. Glucose Transport protein

Km VALUE  Maintains the balance between intracellular
 Concentration of the substrate in which half is bounded and extracellular glucose concentration,
to the enzyme  If intracellular glucose is low, glucose will be
 Lower Km - more specific and has greater affinity to the transported towards the intracellular
enzyme thus, faster phosphorylation environment
 Hexokinase is most specific for glucose since it has the  Liver has an enzyme called glucose-6-
lowest Km value, and is even more specific for glucose phosphatase that allows glucose to be released
when compared to glucokinase.
 Glucokinase is found in the brain; it is specific for
glucose but has higher Km value.
o Higher Km value - brain does not grab glucose
all the time, it depends on the metabolism of
glucose for a neuron.
o Liver & skeletal muscles grab glucose
immediately
 In skeletal muscles: If there is more activity, there
would be more space for carbohydrates to occupy in the
muscles.
o If you eat and eat  no storage for
carbohydrates in muscle  bad.
 Skeletal muscle – lowest Km value
 Hepatic cells – intermediate Km value
 Brain – highest Km in order to maintain the osmolarity IV.HEPATIC FRUCTOSE AND GLUCOSE METABOLISM
o The brain has no space for storage of fuel
sources/energy. If the liver will bring out A. AFTER A MEAL
glucose, the brain always keeps on getting
them.
o There is fixed fuel consumption in the
brain.(e.g: listening attentively and dosing off:
same consumption)
SOURCES OF ENERGY USED BY THE
BODY(100%):

20% (1/5) glucose - BRAIN

40% - SKELETAL MUSCLE (60% fat, 40%

glucose)

40% - HEART, KIDNEYS, SPLEEN (50% fat, 50%

glucose)

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  Fructose can be converted to fatty acids.
 Glucose goes inside the hepatocyte.
 The activity of glucokinase dominate(glycogenesis).
 Increased load of both fructose and glucose will favour
formation of fatty acid.
 Don't eat fruits together with a heavy meal because it
will lead to fat deposition, if glycogen storage has
reached it maximum capacity.
 Glucose is broken down to acetyl coA, then proceeds to
fatty acid synthesis.
 Adapt a meal plan based on the activity
 high intensity, short duration activity: HIGH
glycemic index; LOW glycemic load
 low intensity activity: LOW glycemic index; HIGH
glycemic load
B. BETWEEN MEALS
V. RECALL ON FRUCTOSE METABOLISM, FEEDBACK
MECHANISM
 If there is no more glucose or glycogen, fructose will be
utilized for ATP production
 Between meals, glucose 6-phosphatase is more active.
(glycogenolysis).
C. AFTER SUGAR CONSUMPTION
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• Fructose will undergo fatty acid synthesis
• Glyceraldehyde
 Link between fructose and fatty acid synthesis
 Can be readily converted to glycerol
 Backbone for triglycerides
Brown vs. white sugar
 biochemically not different
 brown sugar: presence of the more impurities
more chromium
 Chromium: facilitates binding of insulin to the
receptor->Lowers blood sugar better
 increased insulin: exhaustion of beta cells
due to increased sugar
 more exerciseconsume the
sugarprotect the beta cell
 If the fuel source is fructose:
 Usual pathway: formation of fructose-6-phosphate
through the glycolytic pathway
 In abundance of fuel (fructose and glucose): the
pathway is directed to the formation of fructose-1-
phosphate
 Technically the fructose-1-phosphate pathway
is not part of the standard glycolytic pathway.
Fructose is not used as a fuel source in this
pathway.
 But if fructose goes to the path of being
fructose-6-phosphate, it can be used as a fuel
source.
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Fructose: Comparing Glucose from Sucrose:

1. When converted to fructose-1-phosphate → yields

glyceraldehyde and Dihydroxyacetone phosphate
(DHAP)
2. When converted to fructose-6-phosphate → yields
glyceraldehyde-3-phosphate and DHAP
o The advantage of the second pathway is that
glyceraldehyde-3-phosphate can be more
readily converted to glycerol. The
glycerolproduced can be used as a backbone
for triglyceride synthesis.
 Glyceraldehyde-3-phosphate in excess is converted to
DHAP, and DHAP would produce pyruvate. Excess
pyruvate will go to fatty acid synthesis.
-This pathway is the one usually followed by
fructose metabolism especially in cases
 High fructose corn syrup is in the form of a very fine
wherein there is excess carbohydrates in the
body. powder a.k.a. Confectioner’s sugar
- Deficiency in carbohydrates (especially - Leading cause of increase in lifestyle
glucose) leads to: fructose following the diseases
fructose-6-phosphate pathway. (The one going  High fructose corn syrup more dangerous than table
up) sugar FRUCTOSE 5X SWEETER THAN GLUCOSE
 When there is excess fructose, Fructose-6-phosphate  fructose as sweetener increases fat
formationincreased obesity
pathway feedback mechanism and inhibition by
 GLUT2 (Glucokinase 2): transporter that facilitates the
PHOSPHOFRUCTOKINASE is bypassed. No glucose is movement of BOTH glucose and fructose inside the cell
metabolized therefore increase in glucose levels.
VI. NEGATIVE FEEDBACK INHIBITION
2 storage forms of fuel:

1. Glycogen: prioritized
2. Fats (Fatty acids): synthesized next when the
glycogen stores are at full capacity

SUMMARY OF FRUCTOSE METABOLISM

 When product concentration is very high, it will elicit a

negative feedback mechanism in order to stop product
formation.
 However, fructose bypass that negative feedback
inhibition and continue to be converted to
glyceraldehyde that serves as the backbone for
triglycerides

REMEMBER: In state of high carbohydrates in the body,

glyceraldehyde-3-phosphate is shunted to the production of fatty
acids.

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VII. FRUCTOSE AND MANNOSE METABOLISM VIII. FRUCTOSE INTAKE

How much fructose can one eat per day?

 20 grams can be absorbed per day

3 pathways:
a. Trigylceride synthesis
 Fructose → Fructose-6-Phosphate → Triglycerides
b. N-Glycan Synthesis
 used for storage
 Complex polysaccharides: D-fructose-6-phosphate is
converted to D-mannose, then D-mannose is coupled
with proteins to form glycoproteins, glycans, and
glycopeptides
c. Xanthine pathway
 leads to the formation of uric acid
 for nucleic acid
 When there is a lot of fructose intake leading
to depletion of ATP with subsequent
production and build-up of AMP. AMP is
converted to IMP then to Inosine,
Hypoxanthine, Xanthine and finally, Uric acid.
 Clinical Significance: eating excess fructose
may lead to development of gouty arthritis
o Hyperuricemia or gouty attacks may
occur in scenarios of too much food in the
system
1
 Equivalent to 4 2 teaspoon or 2 apples
 Pineapple: 4%
 Mango: 16%
 Dry Figs: 23%
 Greater than 20 g is harmful to the liver
 It may cause fat deposition, obesity, insulin
resistance
 Juice and softdrinks are equally high in fructose. Just
one glass has 20–30 grams fructose. That is over the
daily limit!
 One banana has 7.1 grams of fructose. So you can
have two bananas (14.2 grams), your first banana
and ANOTHER banana. But three bananas would be
excessive (21.3 grams).
 Learn to be contented; huwag kain ng kain ng
saging malandi ka, or else you’ll get fat!  :P
 Fructose can be used for TG synthesis which may cause
insulin resistance and affect inflammation.
 Glucose stimulate insulin while fructose does not.
o Too much glucose would cause excess insulin
secretion leading to more weight gain.
o Too much fructose would inhibit negative feedback
leading to further weight gain.
IX. FRUCTOSE METABOLISM
 Fructose enters the liver and undergoes:
a. Glycogenesis – minimal
b. Lipogenesis – main pathway

Other hexoses include:

 Galactose
 converted to galactose-1-phosphate then to
glucose-1-phosphate (a transient stepping stone)
then to glucose-6-phospate, then enters glycolytic
pathway
 The salient biochemical process where galactose,
 Galactinose
fructose and glucose can interact is supposedly the
glycolytic pathway but this only occurs when there
is low carbohydrate in the body.
 If there are too much carbohydrates in the body,
fructose follows the Fructose-1-Phosphate Pathway

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 CHECKPOINT:
T/F
1) Phosphorylation reaction traps them inside the
cell.
2) Hexokinase is a specific component for the
skeletal muscles.
3) Lower Km is more specific and has greater
affinity to the enzyme.
4) GLUT-5 is the cotransporter of glucose.
5) Fructokinase is found in the liver.
6) The priority of hexose metabolism is fat.
7) Dietary monosaccharides undergo hydrolysis to
polysaccharides and disaccharides.
Normal Pathway: Glucose and fructose are metabolized the
8) Eat fruits together with a heavy meal because it
same way.
will not lead to fat deposition.
9) Fructose can be used as a fuel source if it goes
Excess Glucose and Fructose:
to the fructose-6-phosphate pathway.
 Build-up of lipids from glucose 10) When there is excess fructose, Fructose-6-
 Unregulated metabolism of fructose phosphate pathway feedback mechanism and
 Shut down of glucose metabolism inhibition by PHOSPHOFRUCTOKINASE is
bypassed.
That is why: 11) Fructose and glucose both use the transporter
GLUT3 (Glucokinase 3) to move inside a cell.
‒ More eating should be accompanied with more
exercise or better yet less eating with more 12) The Xanthine pathway leads to the formation of
exercise uric acid.
13) Fructose can be used for triglyceride synthesis
Bad effects of Fructose in a Scenario Where There is which may cause insulin resistance and affect
Excess Carbohydrate: inflammation.
14) Glucose stimulates insulin while fructose does
not.
15) If there are too much carbohydrates in the
body, fructose follows the Fructose-6-
Phosphate Pathway.
16) Monosaccharides would go into different
pathways but they will all eventually meet in
the glycolytic pathway.
17) The main pathway of fructose metabolism is
lipogenesis. (T)
18) When converted to fructose-1-phosphate, it
yields glyceraldehyde-3-phosphate and
Dihydroxyacetone phosphate (DHAP).
19) In state of high carbohydrates in the body,
glyceraldehyde-3-phosphate is shunted to the
production of fatty acids.
20) There is fixed fuel consumption in the brain.
Answers:
1. T 6. F 11. F 16. T
2. F 7. F 12. T 17. T
3. T 8. F 13. T 18. F
4. F 9. T 14. T 19. T
5. T 10. T 15. F 20. T
Answers:T, F-protein,T, F-glucokinase,T, F-GLUT-2,T,F-
glucose,F-polysaccharidesand and
‒ Monosaccharides would go into different pathways but disaccharides;monosaccharides,F-Don’t;will lead
they will all eventually meet in the glycolytic pathway.
“Don’t let what you cannot do interfere with what
you can do.” – John Wooden

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