EDITED & RECOMPOSED BY

Liniyanti D.Oswari,MD.,MNS,MSc.
For Block 8
Medical student, Sriwijaya
University

Carbohydrate
Metabolism
Glycolysis
2.3. Biphospoglycerate (2.3.BPG)
Glycogenesis
Glycogenolysis
HMP shunt
Gluconeogenesis
REGULATION OF METABOLISM BY

HORMONES

Carbohydrate Metabolism
Overview
glycogen
pentose
GLUCOSE
other sugars
pyruvate

lactate

acetyl CoA

EtOH

Adipose

Energy
Stores

Glycogen

Glucose
Pentose
Phosphate
Pathway

Ribose-5-phosphate

Glycolysis

Pyruvate

GLYCOLYSIS
Glucose can also be available from

food intake.
Glucose is also stored as glycogen
(glycogenesis).
After gluconeogenesis, glucose is
converted from glycogen in liver or
muscle for glycolysis.
Glycolysis is the break down of a 6 C
glucose sugar to two 3C pyruvate.

Central role of liver in

metabolism
Glucose entering the hepatocyte is

phosphorylated by glucokinase to glucose-6phosphate (G-6-P).

Other monosaccharides are also made to G6-P via gluconeogenesis, then glucose can
be stored as glycogen.
When we need energy, glycolysis converts
G-6-P to pyruvate and acetyl coA to enter
Citric acid cycle to produce ATP energy via
oxidative phosporylation (aerobic
metabolism).

Hexokinase
ADP

Glucose

ATP

Fructose-6-phosphate
ATP

ADP

Fructose-1, 6-biphosphate
Dihydroxyacetone
phosphate (DHAP)

Glyceraldehyde-3phosphate
NAD + Pi
NADH + H+

ADP

Glyceraldehyde-1,
3-bisphosphate
ADP

Glycerol ADP

ATP

ATP

H2O Phospho

ATP

Glycerate-3phosphate

Pyruvate

Glucose-6phosphate

Glycogen
Lactate
Dehydrogenase

Glucose-1phosphate

UDP-glucose

Lactate

Glycolysis:
break down of glucose in cytoplasm

Glycerate-2phosphate

-enolpyruvate
H2 O

Glycolysis: Phase 1 and

2Phase 1: Sugar activation
Two ATP molecules activate glucose into

fructose-1,6-diphosphate

The 1 and 6 indicate which carbon atom to which

they are attached.

Phase 2: Sugar cleavage (splitting)

Fructose-1,6-bisphosphate (6 Cs) is split into
two 3-carbon compounds:

Glyceraldehyde 3-phosphate (GAP)

Glycolysis: Phase 3

Phase 3: Oxidation and ATP formation

The 3-carbon sugars are oxidized (reducing

NAD+); i.e., 2 Hs + NAD

NADH2

Inorganic phosphate groups (Pi) are attached

to each oxidized fragment

The terminal phosphates are cleaved and
captured by ADP to form four ATP molecules
The final products are:
Two pyruvic acid molecules
Two NADH + H+ molecules (reduced NAD+)
A net gain of two ATP molecules

Glycolysis has two stages.

A. An energy investment phase.
Reactions, 1-5. Glucose to two
glyceraldehyde -3-phosphate
molecules. 2 ATPs are invested.
B. An energy payof phase.
Reactions 6-10. two glyceraldehyde
3-phosphate molecules to two
pyruvate plus four ATP molecules.
-- A net of two ATP molecules overal
plus 2 NADH(10 ATP2 ATP= 8 ATP).

GLYCOLYSIS

Glucose
ATP
hexokinase
ADP
Glucose 6-phosphate
phosphoglucoisomerase
Fructose 6-phosphate
ATP
phosphofructokinase
ADP
Fructose 1.6-bisphosphate
aldolase
triose phosphate isomerase
Dihydroxyacetone
Glyceraldehyde

Glyceraldehyde 3-phosphate
glyceraldehyde
NAD+ + Pi
3-phosphate
NADH +
H+
dehydrogenase
1,3-Bisphosphoglycerate

ADP
phosphoglycerate kinase
ATP
3-Phosphoglycerate
phosphoglyceromutase
2-Phosphoglycerate
enolase
H2O
Phosphoenolpyruvate
ADP
pyruvate kinase
ATP

Glycolysis:
Embden-Myerhof
Oxidation of
Pathway
glucose
Products:

2 Pyruvate
2 ATP
2 NADH

Cytosolic

Summary of Energy Relationships

for Glycolysis aerobic
Input = 2 ATP
1. glucose + ATP glucose-6-P
2. fructose-6-P + ATP fructose 1,6
bisphosphate

Output = 4 ATP + 2 NADH

1. 2 glyceraldehyde-3-P + 2 Pi + 2 NAD+
2 (1,3 bisphosphoglycerate) + 2 NADH
2. 2 (1,3 bisphosphoglycerate) + 2 ADP
2 (3-P-glycerate) + 2 ATP
3. 2 PEP + 2 ADP 2 pyruvate + 2 ATP

Net = 2 ATP and 2 NADH( 8 ATP)

Energy Yield From Glycolysis

glucose 6 CO2 = -2840 kJ/mole
2 ATPs produced = 2 x 30.5 =
61 kJ/mole glucose

Energy yield = 61/2840 = 2%

recovered as ATP
- subsequent oxidation of pyruvate and
NADH can recover more of the free
energy from glucose.

Carbohydrate Metabolism

Primarily glucose

All cells can utilize glucose for energy production

Fructose and galactose enter the pathways at various points

Glucose uptake from blood to cells usually mediated by insulin and
transporters

Liver is central site for carbohydrate metabolism

Glucose uptake independent of insulin

The only exporter of glucose

Blood Glucose Homeostasis

Several cell types prefer glucose as energy

source (ex., CNS)
80-100 mg/dl is normal range of blood
glucose in non-ruminant animals
45-65 mg/dl is normal range of blood
glucose in ruminant animals
Uses of glucose:

Energy source for cells

Muscle glycogen

Fates of Glucose

Fed state

Storage as glycogen

Storage as lipids

Liver
Skeletal muscle
Adipose tissue

Fasted state

Metabolized for energy

New glucose synthesized

Synthesis
Synthesis and
and
breakdown
breakdown occur
occur
at
at all
all times
times
regardless
regardless of
of
state...
state...
The
The relative
relative rates
rates
of
of synthesis
synthesis and
and
breakdown
breakdown change
change

High Blood
Glucose

Pancreas
Muscle
Glucose
absorbed

Insulin

Glycogen
Glucose
absorbed

Adipose
Cells
Glucose absorbed

immediately after eating a meal

Glucose Metabolism

Four major metabolic pathways:

Immediate source of energy

Pentophosphate pathway
Glycogen synthesis in liver/muscle
Precursor for triacylglycerol synthesis

Energy status (ATP) of body regulates which

pathway gets energy
Same in ruminants and non-ruminants

Fate of Absorbed Glucose

1st Priority: glycogen storage

2nd Priority: provide energy

Stored in muscle and liver

Oxidized to ATP

3rd Priority: stored as fat

Only excess glucose

Stored as triglycerides in adipose

Glycolysis - Summary
Glucose (6C)
2 ATP
4 ADP
2
ADP

4 ATP
2
NAD
2 NADH +
H

2 Pyruvate
(3C)

Glucose Utilization
Adipose

Energy
Stores

Glycogen

Glucose
Pentose
Phosphate
Pathway

Ribose-5-phosphate

Glycolysis

Pyruvate

Three irreversible kinase

reactions
primarily drive glycolysis forward.

hexokinase or glucokinase
phosphofructokinase
pyruvate kinase
These enzymes will be shown to be
regulate glycolysis as well.

Pyruvate Metabolism

Three fates of pyruvate:

Conversion to lactate (anaerobic)
Conversion to alanine (amino acid)
Entry into the TCA cycle via pyruvate
dehydrogenase pathway (create ATP)

Fate of Product of GlycolysisPyruvate

- Pyruvate is at a central branch
point
in metabolism.
Recall:
Aerobic pathway - through
citric acid cycle and respiration;
this pathway yields far more energy
and will be discussed later.

Cori Cycle
Lactate is
converted
to pyruvate
in the liver

Two anerobic pathways:

- to lactate via lactate dehydrogenase

- to ethanol via ethanol dehydrogena
- Note: both use up NADH produced
so only 2 ATP per glucose consumed

Pyruvate metabolism
Convert

to alanine and export to blood

Glutamate

Ketoglutarate

COO
C

CH 3

COO
Alanineaminotransferase
(AAT)

Pyruvate

Keto acid
acid

HC

NH 3+

CH 3
Alanine

Amino

Pyruvate Dehydrogenase Complex

(PDH)

Prepares pyruvate to enter the TCA cycle

Aerobic Conditions
Electron
Transport

TCA
Cycle

1. Lactate Fermentation
Enzyme = Lactate
Dehydrogenase
COOC=O + NADH + H+
NAD+
CH3

pyruvate
lactate

COOH-C-OH +
CH3

Helps drive glycolysis by using up

NADH
reversible so pyruvate can be
regenerated in alternative
metabolism
lactate fermentation important in
red blood cells, parts of the
retina,
and in skeletal muscle cells
during

-Lactate Dehydrogenase (LDH) has

multiple forms. It is an isozyme.
Two polypeptides M and H come
together to form LDH. It is a tetramer
so a mixture is formed:
M4, M3H, M2H2, MH3 and H4
M M
M H
H H
H H
H H
M M
M M
MM
M H
H H

 Skeletal muscle and liver contain

predominantly the M forms;
heart the H forms. During and
after myocardial
infarction (heart
attack), heart
cells die releasing
LDH into the
circulation.
Diagnostic.

LACTIC ACID (CORI) CYCLE

glucose
glucose
glucose
glucose-6-P
glucose-6-P
glycogen
glycog

ATP
ATP
NADH
Blood
NAD
pyruvate
pyruvate

lactate
lactate
lactate

Liver

Muscle


The liver uses most of this lactate to
make glycogen. Only small amounts
of free glucose released.
Glycogen can be broken down into
glucose when needed.

2.Alcoholic Fermentation
COOC=O
CH3

CO2

CH2OH
H O

C + NADH
CH3 +
CH3
NAD+

pyruvate
acetaldehyde
ethanol
pyruvate decarboxylase-

- pathway is active in yeast.

- second step helps drive glycolysis
-second step is reversible
- reverse is ethanol oxidation,
eventially yields acetate, which
ultimately goes into fat synthesis.
- ethanol acetaldehyde aceta
- humans have alcohol dehydrogenase
in liver which mainly disposes of
ethanol.
- acetaldehyde is reactive and toxic.

Summary Glucose
of Reactions
2 ATP

2 NADH

2 pyruvate
2 NADH
anaerobic
2 ethanol + CO2

2 NADH
anaerobic
2 lactate

2 acetyl CoA + 2
CO2

O2

aerobic

-- REGULATION OF GLYCOLYSIS
1.HEXOKINASE and
GLUCOKINASE
HEXOKINASE

Commiting step in glycolysis:

phosphorylation of glucose.
Inhibited by its product, glucose6-phosphate,
as a response to slowing of glycolysis .
found in all cells of every organism low
specificity for monosaccharides
(simple sugars) i.e., other monosaccharides
can be phosphorylated by hexokinase.

GLUCOKINASE

liver enzyme with high KM (10 mM)fo

glucose so most effective when
glucose levels are very high
not inhibited by glucose 6-phospha
sensitive to high glucose in
circulation from recent meal
so it decreases high level of glucose
in blood by taking glucose into liver

2.

PHOSPHOFRUCTOKINASE
rate limiting for glycolysis
an allosteric multimeric regulatory
enzyme.
Measures adequacy of energy levels

Inhibitors: ATP and citrate

high energy
Activators: ADP, AMP, and
fructose 2,6 bisphosphate
low energy

 ATP inhibits phosphofructose

activity by decreasing fructose
6-phosphate bindingAMP and ADP
reverse ATP inhibition
Fructose 2,6 bisphosphate is a v
important regulator, controlling the
relative flux of carbon through
glycolysis versus gluconeogenesis.
- It also couples these pathways to
hormonal regulation.

3. PYRUVATE KINASE
PEP + ADP Pyruvate + ATP
An allosteric tetramer
-inhibitor: ATP & acetyl CoA &
fatty
acids (alternative fuels for TCA
cycle)

- activator: fructose 1,6bisphosphate

- (feed-forward)
Phosphorylation (inactive form) and
dephosphorylation (active form)
under hormone control.

Siklus 2,3 Biphosphoglicerat

2.3 Biphosphoglycerate(BPG)

Human Hb and binding site for 2,3 BPG

The rate of Glycolysis will influent the affinity

oxygen and Hemoglobine,with the intermediate
2,3 BPG pathway
Disorder in glycolysis will influent the affinity
hemoglobine and oxygen.
Defficiency Piruvat kinase, so the level of 2.3
BPG will increase.
The affinity of oxygen and hemoglobine loose,
and hypoxia in the tissue
Anemia hemolytic.

Deficiency Hexokinase

- Genetic disease

- 2.3 BPG in RBC low

- Affinity Hb and Oxygen is very strong
(abnormal)
- Hypoxia in the tissue

Defficiency Piruvate kinase

(Anemia Hemolitik)

- Blockade The end of glycolytic pathway, The

affinity of oxygen and Hb decrease. turun.
- The production of ATP is not enough, so it
decrease the activity of Na+ & K+, stimulate ion
ATP ase pump.
It will keep the membran cell of RBC.
Defficiency Piruvate Kinase will make RBC
Lysis.

Glycogenesis

Glycogen synthesis
Occurs in cytosol of liver,muscle& kidney
Occurs when blood glucose levels are high
Excess glucose is stored (limited capacity)
liver and muscle are major glycogen storage sites

liver glycogen used to regulate blood glucose levels

brain cells cannot live for > 5 minutes without glucose
muscle glycogen used to fuel an active muscle

CH2OH

CH2OH
O

........
O

CH2OH
O

CH2OH

CH2
O

O
O

-[1-6] linkage
CH2OH
O
O

-[1- 4] linkages

. The glycogen structure showing the glycosidic bonds

Glycogenesis

Liver

710% of wet weight

Use glycogen to export glucose to the bloodstream when
blood sugar is low
Glycogen stores are depleted after proximately 24 hrs of
fasting (in humans)
De novo synthesis of glucose for glycogen

Skeletal muscle

1% of wet weight

More muscle than liver, therefore more glycogen in muscle, overall

Use glycogen (i.e., glucose) for energy only (no export of

glucose to blood)
Use already-made glucose for synthesis of glycogen

Glucose
Hexokinase
(muscle)
Glucokinase
(liver)

ATP
ADP

Glucose-6-phosphate

Phosphoglucomutase

(Glucose)

(Glucose)n+

Glucose-1-P
Uridyltransferase

UDP-glucose

Glucose-1-phosphate
UTP

UDP

Glycogen Synthase

PPi

Pathway of glycogen synthesis (glycogenesis).

Control of enzyme activity

Rate limiting step

Glikogenesis & Glikogenolisis

Glucose anabolism

Glucose storage:
glycogenesis

glycogen formation is
stimulated by insulin
glucose not needed
immediately is stored
in the liver (25%) and
in skeletal muscle
(75%)

Glucose release:
glycogenolysis

converts glycogen to
glucose
occurs between
meals, stimulated by
glucagon and
epinephrine

Glycogenolysis

Glycogen degradation
Occurs in cytosol
Signal that glucose is needed is given by
hormones

epinephrine stimulates glycogen breakdown in

muscle
glucagon which stimulates glycogen breakdown
in liver in response to low BG
used to sustain blood glucose level between meals
and to provide energy during an
emergency/exercise

Glycogen
Pi

glycogen
phosphorylase
Glucose-1-phosphate
phosphoglucomutase

LIVER PATHWAY
glucose-6-phosphatase

Glucose-6-phosphate
glycolysis
(inhibited by lack of
fructose-2,6-bisP

Glycogenolysis and the fate of glycogen in liver and kidney

Glucose
Pi

Glycogen

MUSCLE PATHWAY
Pi

glycogen
phosphorylase
Glucose-1-phosphate
phosphoglucomutase
Glucose-6-phosphate
glycolysis
Pyruvate
pyruvate
dehydrogenase
Acetyl CoA

anaerobic
Lactate
lactate dehydrogenase
citric acid cycle
aerobic

CO2

. Glycogenolysis and the fate of glycogen in muscle .

SIMPLISTIC SUMMARY:
-- Epinephrine and glucagon stimulate
glycogenolysis & inhibit glycogenesis
via a cAMP and a phosphorylation
cascade. release glucose
-- Glycogenesis is stimulated by
insulin in a pathway ending in the
dephosphorylation of glycogen
synthase.
-- Glycogenolysis is also inhibited
via dephosphorylation.
take up glucose

Glycogen Storage Diseases:

A family of serious, although not

necessarily fatal, diseases caused by

mutations in the enzymes involving
in glycogen storage and breakdown.

Glycogen Storage Diseases

Type I: Von Gierke Disease; Glucose-6-phosphatase Defect

Hypoglycemia occurs due to defect of the final step of gluconeogenesis.

This disease, affects only liver and renal tubule cells
Decreased mobilization of glycogen produces hepatomegaly.
Decreased gluconeogenesis causes increased lactate leading to lactic acidemia.

Type V: McArdle Disease; Skeletal Muscle Glycogen Phosphorylase Defect

Skeletal muscle is affected, whereas the liver enzyme is normal.

Temporary weakness and cramping of skeletal muscle occurs after exercise.
There is no rise in blood lactate during strenuous exercise.
Muscle contains a high level of glycogen with normal structure
Type VI: Hers Disease; Liver Glycogen Phosphorylase Defect

Liver is affected, whereas the skeletal muscle enzyme is normal.

Marked hepatomegaly occurs due to a high level of glycogen with normal structure..
Following administration of glucagon, there is no increase in blood glucose.

Pentose Phosphate Pathway=

Hexose
Monophosphat
Shunt
Generation of NADPH and Pentoses
Has 2 functions
1.Generate reducing equivalents NADPH (reduced cosubstrate/
coenzyme) needed for fatty acid synthesis, folate reduction
2. Produce ribose 5-phosphate needed for DNA and RNA
synthesis
Occurs in cytosol of cells particularly important in anabolic
tissues,liver, adrenal cortex, mammary glands and fat tissues
muscle cells do NOT have HMS enzymes

Pentose Phosphate Pathway

Glucose6phosphat
e

6Phosphogluconolactone

6Phosphogluconate
D-Ribulose5phosphate

RNA or
DNA

D-Ribose5phosphate

Oxidative branch

ATP

ADP

Glucose-6-P-dehydrogenase
NADP
NADPH
6-Phosphogluconate

Glucose 6-P

Glucose

NADP

6-Pgluconate dehydrogenase

Glyceraldehyde 3-P

TDP
Fructose 6-P

Transketolase

Non-oxidative branch

Ribulose 5-P

Xylulose 5-P
Glyceraldehyde 3-P

CO2

NADPH

Ribose 5-P (5 carbons)

Transketolase
TDP
Sedoheptulose 7-P (7 carbons)
Transaldolase

Erythrose 4-P

Fructose 6-P

NADPH is used for biosynthetic reactions and glutathione metabolism

Glyceraldehyde-3-P and fructose-6-P return to the glycolytic pathway

A scenario in which the cell requires NADPH but does not require ribose-5-P

Nucleic acids

Glyceraldehyde 3-P

TDP
Fructose 6-P

Transketolase

Ribulose 5-P

Xylulose 5-P
Glyceraldehyde 3-P

Ribose 5-P (5 carbons)

Transketolase
TDP
Sedoheptulose 7-P (7 carbons)
Transaldolase

Erythrose 4-P

Fructose 6-P

Ribose-5-P is the sugar required for the synthesis of nucleic acids

Oxidative branch is feedback inhibited by excess NADPH at glucose-6-P
dehydrogenase
A scenario in which the cell requires ribose-5-P but does not require NADPH

ATP
Glucose

ADP

Glucose-6-P-dehydrogenase
NADP
NADPH
6-Phosphogluconate

Glucose 6-P
Ribulose 5-P

NADP
6-Pgluconate dehydrogenase

CO2

NADPH

Ribose 5-P (5 carbons)

Nucleic acids
A scenario in which the cell requires both NADPH and ribose-5-P

Overview

Function

NADPH production

Reducing power
carrier

Synthetic pathways

Role as cellular
antioxidants

Ribose synthesis

Nucleic acids and

nucleotides

Characteristics: Tissue Distribution

Demand for NADPH

Biosynthetic pathways

FA synthesis (liver, adipose, mammary)

Cholesterol synthesis (liver)
Steroid hormone synthesis (adrenal, ovaries, testes)

Detoxification (Cytochrome P-450 System) liver

Reduced glutathione as an antioxidant (RBC)
Generation of superoxide (neutrophils)

Characteristics:
Oxidative and Non-oxidative Phases
Oxidative phases

Reactions producing
NADPH
Irreversible

Non-oxidative phases

Produces ribose-5-P
Reversible reactions feed
to glycolysis

NADPH producing reactions

Glucose-6-P dehydrogenase
6-P-gluconate dehydrogenase

The Pentose Phosphate Pathway:

Non-oxidative phases

Regulation

Glucose-6-P dehydrogenase

Allosteric Regulation

First step
Rate limiting
Feedback inhibited by NADPH

Inducible enzyme

Induced by insulin

HMS ( Hexose Monophospat Shunt)

Nicotinamide adenine dinucleotide phosphate

phosphorylated form of reduced nicotinamide
adenine dinucleotide (NADH)
generated in a series of reactions comprising
the oxidation-reduction phase of HMS

Ribose 5-phosphate
sugar used as the backbone of DNA and RNA
Cells requirement for ATP (glycolysis) or
NADPH and ribose 5-P (HMS) determines which
path it will take.

Stages of HMS

Reactions occur in 3 main stages

oxidation-reduction

isomerization stage

generation of NADPH
generation of ribose 5-phosphate

carbon bond cleavage-rearrangement stage

conversion of three 5-carbon sugars to two 6-carbon sugars (Fructose

6-phosphate) and one 3-carbon sugar (Glyceraldehyde 3-phosphate)
these series of reactions occur in cells where demand for NADPH is
high

F 6 P can be converted back to G 6 P which can re-enter HMS

Reactions of Stages 1 and 2

G6P is oxidized to 6-phosphoglucono-lactone by G6P

dehydrogenase that uses NADP as coenzyme

6-phosphoglucono is hydrolyzed (addition of water) to 6phosphogluconate

6-phosphogluconate is oxidized by 6 phosphogluconate
dehydrogenase

produces NADPH and 6-phosphoglucono

produces NADPH and ribulose 5 phosphate

Ribulose 5-phosphate is isomerized to ribose 5 phosphate

Regulation of Metabolism Revisited

Allosteric Enzyme Modulation

enzymes can be stimulated or inhibited by certain

compounds
modulators act by altering conformational
structure of their allosteric enzymes

causes shifts between relaxed and tight conformations

relaxed is most active

ratio of ADP (or AMP) to ATP is important in

regulation of energy metabolism

Allosteric Enzyme Modulation

low ADP:ATP ratio signals less need to

produce ATP

inhibition of key enzymes in glycolysis and the

TCA cycle

high ADP:ATP ratio signals need for ATP

activation of the above enzymes
ATP is end product in oxidative catabolism and its
accumulation would signal to decrease catabolic
pathway activity

PFK, PDH, CS, and isocitrate dehydrogenase

Allosteric Enzyme Modulation

ratio of NADH to NAD+ is also important in

regulation

NADH is end product of catabolic pathway

accumulation would signal to decrease activity
diminution would signal to increase activity
key enzymes are affected in glycolytic and TCA
cycle

PK, PDH, CS, isocitrate dehydrogenase and alpha KG

dehydrogenase

Role of NADPH in the RBC

Production of superoxide

Hb-Fe2+-O2 -> Hb-Fe3+ + O2-.

Spontaneous rxn, 1% per hour

O2-. + 2H2O -> 2H2O2

Both O2-. & H2O2 can produce reactive free

radical species, damage cell membranes, and
cause hemolysis

Pentose Phosphate Pathway

Glucose 6-phosphate dehydrogenase deficiency

Detoxification of Superoxide Anion

and Hydrogen Peroxide

Antioxidant enzymes

Superoxide dismutase
Glutathione peroxidase
Glutathione reductase

GLUCONEOGENESIS

--

Definition: the biosynthesis of glucose

from simpler molecules, primarily
pyruvate and its precursors.

pyruvate
lactate
some amino acid skeletons
TCA cycle intermediates

Gluconeogenesis

Occurs within mitochondria

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 G3-P, F-6-P to G-6-P.
Glucose-6-phosphatase converts G-6-P to
glucose in endoplasmic reticulum

The Cori Cycle

Skeletal Muscle
Lactate

LDH, Lactate
Dehydrogenase

blood

Pyruvate

Glucose

Lactate

LDH, Lactate
Dehydrogenase

Pyruvate

Glucose 6phosphate
Hexokinase

Liver

Glucose 6phosphate
blood

Glucose

Glucose 6phosphatase

Metabolism in liver (amino acid for

gluconeogenesis)

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
oxidation when needed.

Gluconeogenesis

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.

General Features

Tissues:

liver (80%)
kidneys (20%)

Subcellular location of
enzymes

pyruvate carboxylase:
mitochondrial
glucose-6-phosphatase:
ER
all other enzymes
cytoplasmic

glucose

glycogen

G-6-P

G-1-P

gluconeogenesis
CYTOSOL

MITOCHONDRIA

F-6-P

NAD+

glycerol

glyceraldehyde 3-P

glutamate

glutamate
-ketoglutarate

NADH+H+

DHAP

malic acid

malic acid

F-1,6BP

Asp

OAA

-ketoglutarate
Asp

ATP
glycerate 3-P

CO2
GDP

phosphoenol
pyruvate
ADP
glycerate 2-P
PK
ATP
NAD+ NADH+H+

lactate

pyruvate

OAA

NADH+H+

GTP

GTP
1.3-bisphospho2/3
glycerate
ADP

NAD+

ADP
CO2
GDP

1/3

phosphoenol
pyruvate

ATP
CO2

pyruvate

Malate Shuttle

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.

Energetics of Gluconeogenesis

Pyruvate Carboxylase

PEP Carboxykinase

2 GTPs

3-P-glycerate kinase

2 ATPs

2 ATPs

Glyceraldehyde-3-P
dehydrogenase

2NADH

Precursors for gluconeogenesis

Glycerol

derived from adipocyte lipolysis

hepatic glycerol kinase

Precursors for gluconeogenesis

Lactate

RBC
muscle
the Cori Cycle

Precursors for gluconeogenesis

Alanine and other amino acids

transamination of pyruvate
pyruvate derived from glycolysis or from amino acid degradation
alanine cycle

Coordinated Regulation of
Gluconeogenesis and Glycolysis

Gluconeogenesis and Glycolysis

are regulated by similar effector
molecues but in the opposite
direction

avoid futile cycles

PK vs PC&PEPCK
PFK-1 vs FDPtase
GK vs G6Ptase

Coordinated Regulation of
Gluconeogenesis and Glycolysis

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

Coordinated Regulation of
Gluconeogenesis and Glycolysis

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

Coordinated Regulation of
Gluconeogenesis and 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

REGULATION OF METABOLISM
BY HORMONES

Feeding and Fasting

The Pancreatic Islet Hormones
Regulation of Fatty Acid Metabolism
Diabetes Mellitus

Feeding and Fasting

As glucose moves via the blood to the liver, insulin from

the cells 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 cells. They have
opposing effects on blood glucose levels.

Starvation

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 (3C)
Pyruvate

- ++
PEPCK Oxaloacetate

PEP
-+
Pyruvate

The Pancreatic Islet Hormones

Hyperglycemia (high blood
glucose) stimulates
Pancreas
Hepatic
artery

Abdominal
aorta

Duodenum

Exocrine Acini

F cell secretes
pancreatic polypeptides
for digestion in
duodenum

Beta cell
secretes insulin

Spleen

Alpha cell
secretes
glucagon

Hypoglycemia (low blood

glucose) stimulates

Delta cell secretes

somatostatin (inhibits
growth hormone)

Insulin

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.

Glucagon

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

Otak Memerlukan
120 gram glucose / hari = 480 calories

Otak dan pilihan

energinya
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?

Bila tidak cukup tidur maka glukosa diotak

jadi sangat rendah.sleep

no sleep

4 mM
glucose

Jadi bila tidak cukup tidur,

maka glukosa otak turun.
Jadi jangan begadang
walaupun besok ujian akhir
biokimia.

Blood Sugar and Its

Regulation

1. The source and fate of blood sugar

origin (income)

fate (outcome)
CO2 + H2O + energy

dietary supply
liver glycogen
non-carbohydrate
(gluconeogenesis)
other saccharides

blood sugar

glycogen

3.89 6.11mmol/L
other saccharides
non-carbohydrates
(lipids and some
>8.8910.00mmol/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 blood glucose concentration is
70-110 mg/dl(3.89
6.11mmol/L ) normally.

2. Regulation of blood sugar level

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.

3. Abnormal Blood Sugar Level

Hyperglycemia: > 200 mg/dl

The renal threshold for glucose:> 200

mg/d

Hypoglycemia: < 40-50 mg/dl

THE REGULATION OF BLOOD

GLUCOSE
Increased Insulin
secretion and
synthesis

Insulin carried
in blood

Intracellular
communication

Receptors

Stimulus

Muscle and fat

cells throughout
body

Beta Cells in
Islets of
Langerhans

Blood
Glucose

Effectors

Glucose
uptake
Response

Negative
Feedback

Efferent
Pathway

Liver
cells

Glucose
synthesis
Glycogen
synthesis

Blood
Glucose
Blood
Glucose

http://www.medbio.info/Horn/Time%203-4/homeostasis_2.htm

Diabetes Mellitus

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.

Criteria for the Diagnosis of Diabetes ADA

(ADA= American Diabetes Association)
A1C 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.

Prediabetes: IFG, IGT, Increased A1C (ADA)

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.

Correlation of HbA1C with Estimated Average

Glucose (eAG)

HbA1c % Mean Blood Glucose Average Plasma Glucose

(mg/dL) (mg/dL)
4 61
65
Non-Diabetic Range
5 92
100
6 124
135

156

170

Target for Diabetes in Control

188
219
251
283

205
240
275
310

Action Suggested according

ADA guideline

8
9
10
11

12 314

345

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

Interpretation

Biochemical complications of
diabetes
Both types of mellitus.
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).

http://www.mhhe.com/biosci/ap/dynamichuman2/content/gifs/0231.gif

Blood Glucose

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

EXCESS OF BLOOD GLUCOSE

Exerts high osmotic

pressure in extracellular
fluid, causing cellular
dehydration
Excess of glucose
begins to be lost from
the body in the urine:
GLYCOSURIA

GLYCOSURIA
>>>

health.howstuffwork
s.

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
thirst.

OTHER SIDE EFFECTS of

POLYURIA

The dehydration 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

POLYPHAGIA

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/

Insulin deficiency >>

metabolic use of FAT

A deficiency of insulin will

accelerate the breakdown of the
bodys 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.

KETOGENESIS>>KETOSIS

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.

Complications of KETOSIS:

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.gi
f

Effects of insulin deficiency on metabolic

use
of fat fat metabolism
Excess
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.

Effects of insulin deficiency on

metabolic use of fat

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.

Other complications of diabetes:

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)

Non-Proliferative
Retinopathy

Blood vessels 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.

Non-Proliferative Diabetic
Retinopathy

Fundus photo of normal macula Hemorrhages in non-proliferative

diabetic retinopathy
http://www.neec.com/Vitreoretinal_Disease_Diabetic_Retinopathy.html

Proliferative
Retinopathy
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.

Proliferative Diabetic
Retinopathy

New blood vessel growth

around optic nerve in

Hemorrhage from new

blood vessel growth in

proliferative diabetic retinopathy proliferative diabetic retinopathy

Side Effects of Excess

Sugar
Loss of vision due to cataracts: Excessive

blood sugar chemically attaches to lens

proteins, causing cloudiness.

BACTERIA C

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.

Periodontitis

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

Latter Stages of Periodontitis

http://www.qualitydentistry.com/dental/periodontal/perio/sperio.html

Damage to the Nerves

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)

Diabetic 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

Diabetic Neuropathy
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.

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

EFFECT
S OF
DECREA
SED
INSULIN
Polydipsia

Hyperglycemia

Glycosuria

Polyuria

Volume
depletion
DIABETIC
COMA

Increased
lipolysis
Increased
free fatty acids
(FFA)

Increased FFA
oxidation (liver)

Ketoacidosis

Glucose and insulin secretion

BLOOD GLUCOSE

PLASMA
INSULIN
CONCENTRATION
5

15
20
10
TIME (MIN)

GLUCOSE TOLERANCE
Glucose tolerance is the bodys 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, triggering the release
of extra insulin.

TOO MUCH OF A GOOD

THING

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 vs. Type II Diabetes

Type I (IDDM)

Type II (NIDDM)

Age at onset

Usually under Usually over 40

40

Body weight

Thin

Usually
overweight

Symptoms

Appear
suddenly

Appear slowly

Insulin produced

None

Too little, or it is
ineffective

Insulin required

Must take
insulin

May require
insulin

Other names

Juvenile onset Adult onset

diabetes
diabetes

How does
exercise
help?
Most of the time
muscle tissue
depends on fatty acids for

http://clear.msu.edu:16080/dennie/clipart/
exercise.gif

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.

The Diabetic
Meal Plan

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.

The Diabetes Food Pyramid differs from

the standard Food Guide Pyramid in the
way that it groups different foods
Because blood glucose is of primary concern
together.
to people with diabetes, the Diabetes Food

Pyramid focuses on the way in which certain

foods affect blood glucose levels.

For example, 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

homeostatic mechanism
in question:

Can you
remember
all of the
biochemical
consequences???

In diabetes, where is
the missing link?

The physical
consequences?
?

http://nema.cap.ed.ac.uk/teaching
/odl/odl5/insulin.jpg

Quite a bit for one little feedback loop, heh

Lactose Intolerance(Lack or absent of Lactase)

Lactase acts as a pair of molecular scissors:
It snips the disaccaride lactose in two simple
sugars, galactose and glucose:

Clinical manifestations Lactose intolerance

Abdominal pain crampy, localized to periumbilical area, or

lower quadrant

Bloated feeling,stomach cramps

Flatulence

Diarrhea

Vomiting

Stools are usually bulky, frothy and watery

Dietary lactose restriction

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

Enzyme replacement

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

Calcium intake

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

Learning Objective

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?

IMT Depkes 2002-2004

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

Kebutuhan
Gambaran energi Manusia
Energi digunakan Kkal/hari

Wanita dewasa normal

Laki-laki dewasa normal
Pasien Bed rest
Bayi baru lahir
Remaja perempuan aktif
Remaja pria aktif

700 2000
2400 2800
1300 1800
350 450
2400 2600
3100 - 3600

Energi yang digunakan

Aktifitas

Duduk sambil istirahat

Berjalan
Lari cepat
Lari jarak jauh/Maraton
Balap sepeda

Kkal/mnt
0.7 2.0
2.0 6.0
15 atau lebih
10 atau lebih
10 atau lebih

Rumus Harris Bennedict

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

Factors Affecting BMR

Increase:

growth
lean body mass & tall
male
Fever, stress
pregnancy/lactation
increase in thyroxin

Thermal Effect of Food

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

Total Energy

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 p
oor teens

TE Example

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

Energy Balance

When E (in) = E (out)

When E (in) < E (out)

no weight change
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

Pengobatan
& perawatan
nutrisi pada Obesitas:
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
dari Olahraga
Meningkatkan
kapasitas
pernafasan.
Memperbaiki
pencernaan &
metabolisme lemak.
Menurunkan lemak
tubuh dan
Menurunkan Berat
badan.
Menaikan
kekekuatan otot dan
tonusnnya.

Memperbaikmood
, menurunkan
gejala
psychological dan
menajamkan
pikiran.
Menurunkan
resiko penyakit
Jantung
Koroner.
Menguatkan
tulang dan
menaikan
fleksibelitas
persendian.
Memperbaiki
sirkuasi darah.

Fig. 5-2, p. 111