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CARBOHYDRATE METABOLISM

ANABOLISM

EDITED BY
Liniyanti D.Oswari,MD.,MNS,MSc.
For Block 7
Medical student, Sriwijaya University
2019
-- GLUCONEOGENESIS --
 

Definition: the biosynthesis of glucose

from simpler molecules, primarily


pyruvate and its precursors.

 pyruvate
 lactate
 some amino acid skeletons
 TCA cycle intermediates
 Occurs within mitochondria
 Occurs mainly in liver and kidneys
 Lactate is made to pyruvate, but this is not the

reverse of glycolysis
 Pyruvate carboxylase converts pyruvate to

Oxaloacetate with CO2


 PEPCK (PEP carboxykinase) converts

oxaloacetate to PEP (Phosphoenol pyruvate to


G-3-P, F-6-P to G-6-P.
 Glucose-6-phosphatase converts G-6-P to

glucose in endoplasmic reticulum


Pyruvate is converted to oxaloacetate
tThe reaction requires ATP and bicarbonate as
substrates
 That should make you think of biotin!
 Biotin is covalently linked to an active site

lysine
 Acetyl-CoA is an allosteric activator
 The mechanism is typical of biotin!
 Regulation: when ATP or acetyl-CoA are high,

pyruvate enters gluconeogenesis


 Note the "conversion problem" in mitochondria
Conversion of oxaloacetate to PEP
 Lots of energy needed to drive this

reaction!
 Energy is provided in 2 ways:

◦ Decarboxylation is a favorable
reaction
◦ GTP is hydrolyzed
 GTP used here is equivalent to an ATP
Conversion of Glucose-6-P to Glucose
 Presence of G-6-Pase in ER of liver and kidney

cells makes gluconeogenesis possible


 Muscle and brain do not do gluconeogenesis
 G-6-P is hydrolyzed as it passes into the ER
 ER vesicles filled with glucose diffuse to the

plasma membrane, fuse with it and open,


releasing glucose into the bloodstream.
 Liver
 Skeletal Muscle
Lactate blood
Lactate
LDH, Lactate LDH, Lactate
Dehydrogenase Dehydrogenase
Pyruvate Pyruvate

Glucose 6- Glucose 6-
phosphate phosphate
Glucose 6-
Hexokinase blood
Glucose Glucose phosphatase
 Amino acids in the liver can also be
converted to pyruvate which is converted to
glucose or acetyl coA.
 Acetyl Co A can be made to fatty acid and
triacylglycerols and stored as fat.
 Fatty acids in the liver can be made to
lipids for storage; or converted to acetyl
CoA via βoxidation when needed.
 Synthesis of glucose from non-
carbohydrate precursors during fasting in
monogastrics
 Glycerol
 Amino acids
 Lactate Supply carbon skeleton
 Pyruvate
 Propionate
 There is no glucose synthesis from fatty acids
 Occurs primarily in liver, but can also occur
in kidneys and small intestine
Carbohydrate Metabolism :Gluconeogenesis

Overview

Glucose may be synthesized from


other starting materials in a
process called gluconeogenesis.
gluconeogenesis glycolysis

phosphatase glucokinase

phosphofructokinase
phosphatase PFK-1

PEP carboxykinase
pyruvate kinase
pyruvate carboxylase

4 ATP, 2 GTP, 2 NADH 2 ATPs produced


needed
How your liver helps you during exercise....
 Recall that vigorous exercise can lead to a

buildup of lactate and NADH, due to oxygen


shortage and the need for more glycolysis
 NADH can be reoxidized during the reduction

of pyruvate to lactate
 Lactate is then returned to the liver, where it

can be reoxidized to pyruvate by liver LDH


 Liver provides glucose to muscle for exercise

and then reprocesses lactate into new glucose


 Lactate
◦ RBC
◦ muscle
◦ the Cori Cycle
Regulation of Gluconeogenesis
Gluconeogenesis and glycolysis are reciprocally regulated
- within a cell one pathway is relatively inactive while the
other is highly active.
The amounts and activities of the distinctive
enzymes of each pathway are controlled.

The rate of glycolysis is determined by the


concentration of glucose.

The rate of gluconeogenesis is determined by the


concentrations of precursors of glucose.
Reciprocal control with glycolysis
 When glycolysis is turned on,

gluconeogenesis should be turned off


 When energy status of cell is high, glycolysis

should be off and pyruvate, etc., should be


used for synthesis and storage of glucose
 When energy status is low, glucose should be

rapidly degraded to provide energy


 The regulated steps of glycolysis are the very

steps that are regulated in the reverse


direction!
AMP stimulates phospho-
fructokinase, whereas ATP and
citrate inhibit it. Fructose 1,6-
bisphosphatase is inhibited by
AMP and activated by citrate.

Fructose 2,6-bisphosphate
strongly stimulates phospho-
fructokinase 1 and inhibits
fructose 1,6-bisphosphatase.

During starvation, gluconeo-


genesis predominates because
the level of F-2,6-BP is very low.

High levels of ATP and alanine,


which signal that the energy
charge is high and that building
blocks are abundant, inhibit the
pyruvate kinase.
ADP inhibits phosphoenol-pyruvate carboxykinase.
Pyruvate carboxylase is
activated by acetyl CoA and Gluconeogenesis is favored when the cell is rich
inhibited by ADP. in biosynthetic precursors and ATP.
Regulation of the Enzymes Amount by Hormones
Hormones affect gene expression primarily by changing the
rate of transcription.

Insulin, which rises subsequent to eating, stimulates the


expression of phosphofructokinase and pyruvate kinase.

Glucagon, which rises during starvation, inhibits the


expression of these enzymes and stimulates the production
of phosphoenolpyruvate carboxykinase and fructose 1,6-
bisphosphatase.

Transcriptional control in eukaryotes is much slower than


allosteric control; it takes hours or days in contrast with
seconds to minutes.
Regulation of Glycogen Metabolism

• Muscle glycogen is fuel for muscle contraction


• Liver glycogen is mostly converted to glucose
for bloodstream transport to other tissues
• Both mobilization and synthesis of glycogen
are regulated by hormones
• Insulin, glucagon and epinephrine regulate
mammalian glycogen metabolism
Hormones Regulate Glycogen Metabolism

Insulin
• Insulin is produced by b-cells of the pancreas
(high levels are associated with the fed state)
• Insulin increases rate of glucose transport
into muscle, adipose tissue via GluT4
transporter
• Insulin stimulates glycogen synthesis in the
liver via the second messenger
phosphatidylinositol
3,4,5-triphosphate (PIP3)
Allosteric and Substrate-Level Control
 Glucose-6-phosphatase is under substrate-

level control, not allosteric control


 The fate of pyruvate depends on acetyl-CoA
 F-1,6-bisPase is inhibited by AMP, activated

by citrate - the reverse of glycolysis


 Fructose-2,6-bisP is an allosteric inhibitor of

F-1,6-bisPase
 Tissues:
◦ liver (80%)
◦ kidneys (20%)
 Subcellular location
of enzymes
◦ pyruvate carboxylase:
mitochondrial
◦ glucose-6-
phosphatase: ER
◦ all other enzymes
cytoplasmic
glucose glycogen
gluconeogenesis
G-6-P G-1-P
CYTOSOL MITOCHONDRIA
F-6-P

F-1,6BP malic acid malic acid


NAD+ glutamate glutamate NAD+

NADH+H+ ¦Á-ketoglutarate ¦Á-ketoglutarate


glyceral- NADH+H+
DHAP dehyde 3-P OAA Asp Asp OAA

GTP GTP
glycerol ADP
1.3-bisphospho-
glycerate 2/3 CO2 CO2
ADP 1/3
GDP GDP
ATP
glycerate 3-P phosphoenol phosphoenol ATP
pyruvate pyruvate
ADP CO2
glycerate 2-P PK
NAD+ NADH+H+ ATP
lactate pyruvate pyruvate
 OAA produced in
mitochondria
 mitochondrial
membrane impermeable
to OAA
 malate transporter in
mito. Membrane
 malate dehydrogenase
in both mito and cyto
 NADH produced in cyto
also used in
gluconeogenesis.
 Pyruvate Carboxylase
◦ 2 ATPs
 PEP Carboxykinase
◦ 2 GTPs
 3-P-glycerate kinase
◦ 2 ATPs
 Glyceraldehyde-3-P
dehydrogenase
◦ 2NADH
 Glycerol
◦ derived from adipocyte lipolysis
◦ hepatic glycerol kinase
 Alanine and other amino acids
◦ transamination of pyruvate
◦ pyruvate derived from glycolysis or from amino acid
degradation
◦ alanine cycle
 Gluconeogenesis and Glycolysis
are regulated by similar effector
molecues but in the opposite
direction
◦ avoid futile cycles
 PK vs PC&PEPCK
 PFK-1 vs FDP’tase
 GK vs G6P’tase
 Regulation of enzyme
quantity
 Fasting: glucagon, cortisol
◦ induces gluconeogenic
enzymes
◦ represses glycolytic enzymes
◦ liver making glucose
 Feeding: insulin
◦ induces glycolytic enzymes
◦ represses gluconeogenic
enzymes
◦ liver using glucose
 Short-term Hormonal
Effects
◦ Glucagon, Insulin
 cAMP & F2,6P2
 PFK-2 & FBPase-2
◦ A Bifunctional enzyme
◦ cAMP
 Inactivates PFK-2
 Activates FBPase-2
 Decreases F2,6P2
 Reduces activation of PFK-1
 Reduces inhibition of
FBPase-1
 Low blood sugar results in
◦ Hi gluconeogenesis
◦ Lo glycolysis
 Allosteric Effects
 Pyruvate kinase vs Pyruvate carboxylase
◦ PK - Inhibited by ATP and alanine
◦ PC - Activated by acetyl CoA
◦ Fasting results in gluconeogenesis
 PFK-1 vs FBPase-1
◦ FBPase-1 inhibited by AMP & F2,6P2
◦ PFK-1 activated by AMP and & F2,6P2
◦ Feeding results in glycolysis
 Feeding and Fasting
 The Pancreatic Islet Hormones
 Regulation of Fatty Acid

Metabolism
 Diabetes Mellitus
 As glucose moves via the blood to the liver,
insulin from the βcells in the pancreas is
released to promote glucose uptake by muscle
and adipose (for fat storage), and formation of
glycogen in liver. Insulin also induce protein
synthesis.
 When the nutrient flow from intestine
diminishes (fasting), blood glucose and insulin
drop to normal and glucagon is released to
prevent hypoglycemia by promoting
glycogenolysis and gluconeogenesis in the liver.
 Insulin can depress glycagon in αcells. They
have opposing effects on blood glucose levels.
 Fuels change from glucose to fatty acids to
ketone bodies
FASTING Well-fed
Glucose -- INSULIN
INSULIN ++ Glucose

G-6-P Glucagon --
++ Glucagon G-6-P

Fructose-6-P Fructose-6-P

Fructose-1, 6- bis-P Fructose-1, 6- bis-P


Cortisol
Cortisol
- ++ PEP
PEPCK Oxaloacetate
-+
Pyruvate Pyruvate
The Pancreatic Islet Hormones
F cell secretes pancreatic
Hyperglycemia (high blood polypeptides for digestion
glucose) stimulates in duodenum
Exocrine Acini
Pancreas
Beta cell secretes
Hepatic insulin
artery

Spleen
Abdominal
aorta
Alpha cell
Duodenum secretes
glucagon
Delta cell secretes
Hypoglycemia (low blood
somatostatin (inhibits
glucose) stimulates
growth hormone)
 Increase glucose uptake in cells.
 Convert glucose to glycogen (glycogenesis).
 Increase amino acid uptake and protein

synthesis.
 Promote lipogenesis.
 Slow down gluconeogenesis and

glycogenolysis.
 Blood glucose level drops
 Hypoglycemia inhibits release of insulin.
 Acts on hepatocytes.
 Converts glycogen to glucose

(glycogenolysis).
 Form glucose from lactic acid and amino

acids (gluconeogenesis).
 Glucose released from liver to make blood

glucose increase to normal.


 Hyperglycemia inhibits release of glucagon.
http://www.medbio.info/Horn/Time%203-4/homeostasis_2.htm
http://www.medbio.info/Horn/Tim
e%203-4/homeostasis_2.htm
The Brain use glucose for its Energy
120 gram glucose / day = 480 calories
Kebutuhan kalori otak 120 g/ hari glukosa, Hanya
Glukosa (Kecuali Bila tidak ada glukosa maka dari
Benda-benda keton yang berasal dari lemak dan
protein tubuh dg proses Gluconeogenesis)
 Dalam keadaan istirahat memerlukan konsumpsi
oksigen 20% dari kebutuhan total tubuh.
Mengapa Otak memerlukan energi sebesar itu?
Bagaimana keterlibatan transport Na+K+?
 Tapi otak tidak ada Glikogen & tidak bisa
membentuk glukosa sendiri, kenapa?
sleep

no sleep

4 mM
glucose

Jadi bila tidak cukup tidur,


maka glukosa otak turun.
Jadi jangan begadang
walaupun besok ujian
biokimia.
Blood Sugar and Its
Regulation
Regulation of Hexose Transporters
Several glucose transporters (GluT) mediate the thermodynamically downhill
movement of glucose across the plasma membranes of animal cells.

GluT is a family of 5 hexose transporters.


Each member of this protein family consists of a single polypeptide chain
forming 12 transmembrane segments.

GLUT1 and GLUT3, present


in erythrocytes, endothelial,
neuronal and some others
mammalian cells, are
responsible for basal glucose
uptake. Their Km value for
glucose is about 1 mM.
GLUT1 and GLUT3 continually
transport glucose into cells at
an essentially constant rate.
GLUT2, present in liver and pancreatic -cells has a very
high Km value for glucose (15-20 mM).

Glucose enters these tissues at a biologically significant


rate only when there is much glucose in the blood.

GLUT4, which has a Km value of 5 mM, transports glucose


into muscle and fat cells.
The presence of insulin leads to a rapid increase in the
number of GLUT4 transporters in the plasma membrane.
Insulin promotes the uptake of glucose by muscle and fat.
The amount of this transporter present in muscle
membranes increases in response to endurance exercise
training.

GLUT5, present in the small intestine, functions primarily


as a fructose transporter.
1. The source and fate of blood sugar

origin (income) fate (outcome)


dietary supply CO2 + H2O + energy

liver glycogen glycogen


blood sugar
3.89¡« 6.11mmol/L
non-carbohydrate
(gluconeogenesis) other saccharides

non-carbohydrates
other saccharides (lipids and some
>8.89¡« 10.00mmol/L amino acids)
(threshold of kidney)

urine glucose
Blood sugar level must be maintained
within a limited range to ensure the
supply of glucose to brain.

The Fasting blood glucose


concentration is 70-110 mg/dl(3.89 ~
6.11mmol/L ) normally.
Threshold of the Kidney: 160- 180
mg/dl = 8.89-10 mmol/L ( > 200
mg/dl)
* 1 mmol/L= 18 mg/dl
http://www.medbio.info/Horn/Time%203-4/homeostasis_2.htm
1 ) insulin:for decreasing blood sugar levels.
2 ) glucagon: for increasing blood sugar
levels.
3 ) glucocorticoid: for increasing blood sugar
levels.
4 ) adrenaline:for increasing blood sugar
levels.
 Hyperglycemia: > 200 mg/dl
 The renal threshold for glucose:> 200 mg/d

 Hypoglycemia: < 40-50 mg/dl


Increased Insulin
secretion and
synthesis
Efferent
Insulin carried Pathway
Intracellular in blood
communication

Muscle and fat Liver


cells throughout Effectors
cells
Beta Cells in body
Receptors Islets of
Langerhans
Glucose Glucose
uptake synthesis
Glycogen
Response
Blood synthesis
Stimulus
Glucose Blood
Negative Glucose
Feedback
Blood
Glucose
 Caused by deficiency of insulin secretion or
actions
 Type I diabetes (10%) is insulin-dependent
(IDDM), starts early in life and could become
very severe. Due to insufficient insulin
secretion and thus injection of insulin is
required to save the patients’ life.
 Type II diabetes (90%) is non-insulin
dependent, NIDDM, which is slow to develop
with milder symptoms. Insulin is produced
but the cells are not responding (insulin
resistant), causing many complications
including obesity.
HbA1C ≥6.5%
OR
Fasting plasma glucose (FPG)
≥126 mg/dl (7.0 mmol/l)
*Fasting : no calorie intake at least 8 hours
OR
Two-hour plasma glucose ≥200 mg/dl
(11.1 mmol/l) during an OGTT
OR
A random plasma glucose ≥200 mg/dl
(11.1 mmol/l)
ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 2.
Categories of increased risk for diabetes
(Prediabetes)*
FPG 100-125 mg/dl (5.6-6.9 mmol/l): IFG
or
2-h plasma glucose in the 75-g OGTT
140-199 mg/dl (7.8-11.0 mmol/l): IGT
or
A1C 5.7-6.4%
*For all three tests, risk is continuous, extending below the lower limit of a range and becoming
disproportionately greater at higher ends of the range.

ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 3.


 HbA1c % Mean Blood Glucose Average Plasma Glucose
Interpretation
 (mg/dL) (mg/dL)
 4 61 65 Non-Diabetic Range
 5 92 100
 6 124 135

 7 156 170 Target for Diabetes in


Control Action Suggested according ADA
guideline

 8 188 205
 9 219 240
 10 251 275
 11 283 310
 12 314 345

 * Sumber : Diabetes Care : 2002 : 25: 275-8.


 Both types of diabetes fail to uptake glucose,
leading to hyperglycemia. Other symptoms of
diabetes include thirst and frequent urination.
 In IDDM, excessive glucagon level (due to lower
insulin level) also reduces the level of F-2,6-BP in
the liver, and inhibits glycolysis.
 Gluconeogenesis and glycogen breakdown are also
induced.
 NIDDM produces excessive amount of glucose in
blood leading to glucosuria.
 Excessive glucose is thus produced into the blood
leading to hyperglycemia (> 200mg/dl), even with
glucose excreted in urine (hence named mellitus).
 Fasting blood glucose concentration (person
who has not eaten in the past 3-4 hours)
◦ Normal person: 80 - 90 mg / 100 ml
◦ Diabetic patient: 110 - 140 mg / 100 ml
 After a meal:

◦ Normal person: 120 - 140 mg / 100 ml


◦ Diabetic patient: < 200 mg / 100 ml
 Exerts high osmotic
pressure in
extracellular fluid,
causing cellular
dehydration
 Excess of glucose

begins to be lost
from the body in the
urine: GLYCOSURIA
 Excessive glucose in the
kidney filtrate acts as
an osmotic diuretic,
inhibiting water
reabsorption resulting in
POLYURIA: huge urine
output >>> decreased
blood volume and
dehydration.

 Dehydration stimulates
hypothalamic thirst
centers, causing
POLYDIPSIA: excessive
health.howstuffworks. thirst.
com/ diabetes1.htm
 Thedehydration resulting from
polyuria also leads to dry skin.

 During a period of dehydration,


blurred vision can be caused by
fluctuations in the amount of
glucose and water in the lenses of
the eyes.
http://www.nws.noaa.gov/sec508/htm/low_vision.htm
 POLYURIA, POLYDYPSIA,
& POLYPHAGIA=
THE 3 CARDINAL SIGNS OF DIABETES
 POLYPHAGIA: excessive hunger and food
consumption, a sign that the person is
“starving in the land of plenty.” That is,
although plenty of glucose is available, it
cannot be used, and the cells begin to
starve.
 Without fuel, cells cannot produce energy
>> fatigue and weight loss.http://clear.msu.edu:16080/dennie/clipart/
 A deficiency of insulin will accelerate
the breakdown of the body’s fat
reserves for fuel.
 Free fatty acids become the main

energy substrate for all tissues


except the brain.
 Increased lipolysis results in the

production of organic acids called


ketones (KETOGENESIS) in the liver.
 The increased ketones in the blood
lower the pH of blood, resulting in a
form of acidosis called KETOSIS, or
ketoacidosis.
 Ketones are excreted in the urine:
KETONURIA.
 Serious electrolyte losses also occur as the body
rids itself of excess ketones.

 Ketones are negatively charged and carry


positive ions out with them.

 Sodium and potassium are also lost from the


body; because of the electrolyte imbalance,
the person get abdominal pains and
may vomit, and the stress
reaction spirals even higher.

 Can result in coma, death


http://www.sla.purdue.edu/academic/fll/JapanProj/FLClipart/Medical/vomit.gif
 Excess fat metabolism
leads to an increase in
plasma cholesterol >>>
increased plaque
formation on the walls
of blood vessels.

 Leads to atherosclerosis
& other cardiovascular
problems: cerebrovascular
insufficiency, ischemic heart
disease, peripheral vascular
disease, and gangrene.
 Degenerative changes
in cardiac circulation
can lead to early heart
attacks. Heart attacks
are 3-5 times more
likely in diabetic
individuals than in
nondiabetic individuals.
The most common
cause of death with
diabetes mellitus is
myocardial infarction.
 A reduction in blood flow to the feet can
lead to tissue death, ulceration, infection, and
loss
of toes or a major portion
of one or both feet.
 Damage to renal blood

vessels can cause severe


kidney problems.
(Nephropathy)
 Damage to blood vessels
of the retina can also cause
blindness. (Retinopathy)
http://my.diabetovalens.com/infocus/feafeb0404.asp
 Bloodvessels in the retina leak and
hemorrhage. Patient may notice a
decrease in vision if the swelling and
hemorrhage affect the macula.

 Macula edema is the most common


cause of visual loss in diabetic
retinopathy.
Fundus photo of normal macula Hemorrhages in non-proliferative
diabetic retinopathy
http://www.neec.com/Vitreoretinal_Disease_Diabetic_Retinopathy.html
New blood vessels grow in the
eye.

These new blood vessels tend to


bleed and leak causing vision
loss.

These new blood vessels may


also pull on the retina causing
retinal detachment.
New blood vessel growth Hemorrhage from new
around optic nerve in blood vessel growth in
proliferative diabetic retinopathy proliferative diabetic retinopathy
http://www.neec.com/Vitreoretinal_Disease_Diabetic_Retinopathy.html
 Loss of vision due to cataracts: Excessive
blood sugar chemically attaches to lens
proteins, causingBACTERIA
cloudiness.
CELLS

 Skin infections sometimes


occur because excess sugar
in the blood suppresses the
natural defense mechanism
like the action of
white blood
cells. And sugar is an
excellent food for bacteria
for food to grow in.
 High blood glucose also helps
bacteria in the mouth to grow,
making tooth and gum problems
worse.

 Gingivitis: bacteria grow in the


shallow pocket where the tooth
and gum meets; gum begins to
pull away from the tooth.
Progresses to:

 Periodontitis: infection causes


actual bone loss, teeth begin to
pull away from the jaw itself
http://www.stevedds.com/periodon.htm
http://www.qualitydentistry.com/dental/periodontal/perio/sperio.html
 Numbness and tingling in
feet and night leg cramps
may result from nerve
damage due to prolonged
high glucose levels that
cause changes in the
nerves and “neuron
starvation” from lack of
cellular glucose.

 Nerve damage can also


lead to a loss of the ability
to feel pain in the feet,
leading to undue
pressure>>calluses>>
ulceration. (Neuropathy)
 Neuropathy can result in two sets of what
appear to be contradictory problems. Most
patients who have neuropathy have one
these problems but some can be affected by
both:

1) symptoms of pain, burning, pins and


needles or numbness which lead to
discomfort

2) loss of ability to feel pain and


other sensation which leads to
neuropathic ulceration
Patients with neuropathy
lose their sensation of
pain. As a result, they
exert a lot of pressure at
one spot under the foot
when they walk, building
up a callus at that site
without causing
discomfort.

The pressure becomes so


high that eventually it
causes breakdown of
tissues and ulceration.
www.thefootclinic.ca/services_diabetic.php
A TYPICAL NEUROPATHIC ULCER IS…

1) PAINLESS

2) SURROUNDED BY
CALLUS

3) ASSOCIATED
WITH GOOD FOOT
PULSES
(BECAUSE THE
CIRCULATION IS
NORMAL)

4) AT THE BOTTOM
OF THE FOOT
& TIPS OF TOES

ww.diabetes.usyd.edu.au/foot/Neurop1.html www.thefootclinic.ca/services_diabetic.php
INSULIN
DEFICIENCY

Polyphagia Hyperglycemia

Increased
lipolysis
EFFECT Glycosuria
S OF
DECREA Increased
SED free fatty acids
Polyuria (FFA)
INSULIN

Increased FFA
Volume
Polydipsia oxidation (liver)
depletion

DIABETIC
Ketoacidosis
COMA
BLOOD GLUCOSE

PLASMA
INSULIN
CONCENTRATION

5 10 15 20
TIME (MIN)
 Glucose tolerance is the body’s ability to manage its
blood sugar level within normal range. The Cori cycle is a
strategy used by
the body to accomplish
this.
 The blood sugar of
normal individuals
can sometimes drop
to the hypoglycemic
level.
◦ This can even be
caused by ingesting
too much sugar, trig-
gering the release
of extra insulin.
 Diabetics use insulin injections to treat
high blood glucose levels. It is essential
that blood glucose levels always be
maintained above a critical level.
 Brain cells use only glucose for

energy. When blood glucose levels fall


too low (20 to 50 mg/ml), symptoms of
hypoglycemic shock develop – nervous
irritability leading to
fainting, seizures and coma
Type I (IDDM) Type II (NIDDM)
Age at onset Usually under Usually over 40
40
Body weight Thin Usually
overweight
Symptoms Appear Appear slowly
suddenly
Insulin produced None Too little, or it is
ineffective
Insulin required Must take May require
insulin insulin
Other names Juvenile onset Adult onset
diabetes diabetes
Most of the time muscle tissue
depends on fatty acids for energy
 Under two conditions muscles use large amounts of
glucose:
◦ During moderate or heavy exercise (muscle
fibers become permeable to glucose even in
the absence of insulin– important in Type I)
◦ During the few hours after a meal (while
pancreas is secreting more insulin–
important in Type II). Most of the glucose is
stored as muscle glycogen.
http://shots.oxo.li/food/vegetables.jpg

 Under this plan, 60 to 70 percent of your


total daily calories should come from
grains, beans, and starchy vegetables,
with the rest being meat, cheese, fish
and other proteins.

 Fats, oils, and sweets should be used


sparingly. The Diabetes Food Pyramid
suggests the following daily servings of
food for people with diabetes:
DIABETES FOOD
PYRAMID

© Copyright 2002 American Diabetes Association.


 Because blood glucose is of primary concern
to people with diabetes, the Diabetes Food
Pyramid focuses on the way in which certain
foods affect blood glucose levels.
 Forexample, in the standard pyramid,
beans and legumes are grouped with meats,
due to their protein content. In the diabetes
pyramid, however, beans are grouped with
starches, because they affect blood glucose
in the same way that starchy foods do.
One final look at the In diabetes, where is
homeostatic mechanism the missing link?
in question:

Can you The physical


remember consequences?
all of the ?
biochemical
consequences???

http://nema.cap.ed.ac.uk/teaching
/odl/odl5/insulin.jpg
Quite a bit for one little feedback loop, heh?
 Lactase acts as a pair of molecular scissors:
 It snips the disaccaride lactose in two simple

sugars, galactose and glucose:


 Abdominal pain – crampy, localized to periumbilical
area, or lower quadrant
Bloated feeling,stomach cramps
 Flatulence

 Diarrhea

 Vomiting

 Stools are usually bulky, frothy and watery


 Highest concentration in milk and ice-cream, much
lower quantities in cheese

 Complete restriction of lactose-containing foods


should be necessary for a limited period to
ascertain the specificity of the diagnosis

 Since patients can tolerate graded increases in


lactose intake, small quantities of lactose may
subsequently be reintroduced into the diet, with
careful attention to development of symptoms
 Commercially available “lactase” preparations
(bacterial or yeast beta galactosidases)

 Lactaid, Lactrase, LactAce, DairyEase and


Lactrol

 Start with two Lactaid tablets with lactose


ingestion, and adjust both the Lactaid dose
and the lactose load to tolerance
 Avoidance of milk and other dairy products can
lead to reduced calcium intake, and increase in
risk of osteoporosis and fracture
 Calcium carbonate
 Tums – popular and effective
 Infants and young children – liquid calcium
gluconate
 Yogurt containing lactose is well tolerated by the
patients. The yogurt contains live cultures of
bacteria that produce lactase
 Compare Aerobic & anaerobic Glycolysis
 Compare gluconeogenesis and glycogenolysis,
and explain how insulin & Glucagon affects
these processes.
 What are the role of HMP Shunt in our body
 How the Carbohydrate & Fat metabolism di
Diabetic Patients.
 Why diabetic patient easy suffer Ketoacidosis
 Explain the consequences of using low
carbohydrate and high protein diet for weigh
loss plan.
 What is the role of leptine on dieting?
 Why untreated diabetes may die?
 Cara Menghitung IMT(Index Massa
Tubuh)
 IMT=Berat Badan (Kg)
 Tinggi Badan(m)2

 Arti IMT(BMI= Body Mass Index):


 < 17.0 = Sangat kurus
 17.0 - 18.4 = Kurus
 18.5 - 25.0 = Normal
 25.1 - 27.0 = Gemuk
 > 27.0 = Obes
 Gambaran Energi digunakan Kkal/hari
 Wanita dewasa normal 700 – 2000
 Laki-laki dewasa normal 2400 – 2800
 Pasien Bed rest ` 1300 – 1800
 Bayi baru lahir 350 – 450
 Remaja perempuan aktif 2400 – 2600
 Remaja pria aktif 3100 - 3600
 Aktifitas Kkal/mnt
 Duduk sambil istirahat 0.7 – 2.0
 Berjalan 2.0 – 6.0
 Lari cepat 15 atau lebih
 Lari jarak jauh/Maraton 10 atau lebih
 Balap sepeda 10 atau lebih
 Frequently the calculated BMR is referred to as
 BEE = Basal Energy expenditure
 Harris Bennedict
 BEE female: 655 + 9.7( W kg) + 1.85 (Ht cm) –

4.7 (Age)

 BEE male: 66.5 + 13.75 (W kg) + 5 (Hg cm) –


6.8 (A)
 Total Energy: BEE + Physical activity + TEF
 Increase:
◦ growth
◦ lean body mass & tall
◦ male
◦ Fever, stress
◦ pregnancy/lactation
◦ increase in thyroxin
 TEF = Thermal effect of food
 Increased energy expenditure
after a meal.
 5-10% of BMR
 Cost of digestion, absorption, &
assimilation of nutrients
 Ex: 5% x 1320 = 60 Cal
 TE = BMR +TEF + Activities
 Activities: Any voluntary activities
◦ Sedentary 25-35% BMR
◦ Light 35-50%
◦ Moderate 50-70%
◦ Heavy >70%
◦ http://www.americaonthemove.org/
◦ USATODAY.com - Study: Obesity rises faster in poor
teens
 If BMR = 1200
 Then TEF x 0.1 = 120
 If Activity is moderate = 1200 x 0.5 = 600
 Then TE = BMR +TEF + Activity
 TE = 1200 + 120 + 600 = 1920
 When E (in) = E (out)
◦ no weight change
 When E (in) < E (out)
◦ weight loss
 When E (in) > E (out)
◦ weight gain
Tujuan Pengelolaan Obesitas
1) Menurunkan BB sekitar 5-10% dari BB awal, dan bila ada
indikasi dapat diteruskan sampai BMI  25 atau BMI  26.9
2) Mencegah terjadinya Sindroma Yoyo, ialah meningkatnya
BB kembali yang oleh karena disiplin penderita yang turun
3) Memperbaiki penyakit komorbid yang ada
4) Memperbaiki Kualitas Hidup
 Sasaran dari intervensi adalah:
 1. Penurunan lemak tubuh untuk mencapai berat badan
diantara 20% Berat badan ideal
 2. Jangan Turunkan BB dengan drastis. (Maksimal 0.5-1
kg/mg)
 3.Buatlah kebiasaan makan yang lebih sehat. (Tinggi serat,
rendah kalori, rendah lemak dan gula)
 4. Cegah kehilangan otot selama penurunan berat badan.
 5.Modifikasi Prilaku & Olahraga teratur
 6. Pertahankan penurunan berat badan
 7. Bila tidak berhasil gunakan Obat
Sibutramin (Reductil)- Sudah ditarik tahun 2010
Orlystat
Penggunaan Teh ( diuretika & stimulansia)
Keuntungan Memperbaik”mood,”
dari Olahraga menurunkan gejala
psychological dan
Meningkatkan menajamkan
kapasitas pikiran.
pernafasan. Menurunkan
Memperbaiki resiko penyakit
pencernaan & Jantung
metabolisme lemak. Koroner.
Menurunkan lemak
tubuh dan Menguatkan
Menurunkan Berat tulang dan
badan. menaikan
fleksibelitas
Menaikan kekekuatan persendian.
otot dan tonusnnya.
Memperbaiki
sirkuasi darah.

Fig. 5-2, p. 111


References for Further Readings:
Latest editions of:
•Biochemistry by L. Stryer, Freeman & Company New
York ….
•Harper’s Biochemistry by R.K. Murray, D.K.
Granner, P.A. Mayes & V.W. Rodwell. Biochemistry.
Appleton & Lange, New York, Connecticut, California.
•Biochemistry by T. Mckee & J. Mckee, Wm. C. Brown
Publishers, London, Madrid, Tokyo ….
•Biochemistry by I.D.K. Halkerston, Second Edition,
John Wiley & Sons Inc., Williams E Wilkins, USA.
• Textbook of Biochemistry With clinical Correlations
by T.M. Devlin, Wiley-Liss Publication, New York,
Toronto ….
•Biochemistry Illustrated by P.N. Campbell & A.D.
Smith, Longman Group UK Ltd,Dr.UK.
Mohamed Z Gad September 25, 2019 11