Nutrisi dan Pertumbuhan

Mechanisms of
Nutritional-related
Diseases
Agussalim Bukhari, MD, Ph.D
Nutrition Department School of Medicine
Hasanuddin University
@2008

Objective Learning
 To understand mechanism of Nutritional related
Diseases
 To be able to explain types of Malnutrition
 To comprehend Basic of Clinical Nutrition
 To Understand Metabolism of Macronutrients
(Carbohydrate Protein, and Fat)
 To Understand Metabolism of Micronutrients
(Vitamin dan Mineral) and water
 To comprehend Nutrient Interrelation
2

Disease
Environment/
Agents:
Microorganism
Chemical substance
Nutrition
Trauma
Physical stressor
Host:
Genetic
Immunity
Nutrition
Psychological factor
Behavior
Degeneratif/aging
3

Patomechanism of Disease
 Trauma
 Infection
 Inflammation
 Immune responce
 Hemodynamic disorders (ischemic, infark,
thrombosis, shock)
 Neoplasm
 Genetic disorder
 Nutrition, Environment, and lifestyle
4

Daftar Masalah Gizi (SKDI)
 Nafsu Makan Hilang/Kurang
 Gangguan Gizi (Gizi buruk, Kurang, Lebih
(obesitas))
 Berat Bayi Lahir rendah
 Penurunan berat badan mendadak/drastis
5

Level Kompetensi Dokter (SKDI)
 Level 1: Mengenali dan menjelaskan
 Level 2: Mendiagnosis dan merujuk
 Level 3: Mendiagnosis, melakukan
penatalaksanaan awal dan merujuk
 Level 3A: Kasus Bukan gawat darurat
 Level 3B: Kasus Gawat Darurat
 Level 4: Mendiagnosis, melakukan
penatalaksanaan secara mandiri dan Tuntas
 Level 4 A: dicapai saat lulus dokter
 Level 4 B: dicapai setelah internship dan PKB 6

Level Kompetensi Pokok Bahasan Gizi
7
TOPIK Level Kompetensi Blok
Anoreksia Nervosa 2 Neuropsikiatri
Bulimia 2 Neuropsikiatri
Pica 2 Neuropsikiatri
Alergi Makanan 4A Imun-hema
Intoleransi makanan 4A Imunhema
Keracunan Makanan 4A Emergency?/Gastrohep?
Anemia def. besi 4A Imunhema
Malnutrisi energi protein 4A BMD/MDP/CSL1
Def. Vitamin 4A BMD/MDP/CSL1
Def. Mineral 4A BMD/MDP/CSL1
Dislipidemia 4A endokrin
Obesitas 4A Endokrin
Hiperurisemia 4A Musculo

8
Malnutrition
Undernutrition Overnutrition

Optimal
Nutritional status
Normal Immune
Function Immune activation,
Susceptible to
Inflammatory disease
Overnutrition
Undernutrition
CORRELATION BETWEEN NUTRITIONAL STATUS AND IMMUNE FUNCTION
Immune suppression
Susceptible to Infection
9

Pathogeneses of Nutritional
related Diseases
 Malnutrition
 Starvation
 Undernutrition
 Specific Deficiency
 Imbalance
 overnutrition
 Toxicity
 Vitamin
 Mineral
 Amino acid (Genetic disorder e.g. phenylketonuria)
10

Malnutrition-related Diseases
 PEM: marasmus,
kwashirkor
 Vitamin deficiency
diseases: Beriberi (B1),
scurvy (vit C),
xerophthalmia (vit A)
 Mineral deficiency
diseases: Anemia (Fe),
Osteoporosis (Ca)
 Obesity related diseases :
Metabolic syndrome
(diabetes, CVD,
Hyperlipidemia,
Hypertension),
Osteoarthritis, Gout,
Cancer,
 Hypervitaminosis
 Mineral toxicity
Undernutrition Overnutrition
Food Allergy, Food Intolerance, Food Poisoning
11

Pathogeneses of Nutritional
related Diseases
OVERNUTRITION
NUTRIENTS BODY
UNDERNUTRITION
P
R
I
M
A
R
Y
S
E
C
O
N
D
A
R
Y
12

Ethiology of Nutritional
Deficiency
1. InadequateIntake(Primary Cause)
Secondary Cause
2. Malabsorption
3. InadequateUtilisation---lack of enzymes
4. Increased Requirement(Pregnancy)
5. Increased Excretion (Liver Disease)
6. Inadequatemobilisation from storage (i.e Ferritin in
inflammatorydisease)
13

Anatomic
Lesions
Functional
Changes
Biochemical
Lesions
Tissue
Depletion
Nutritional
Inadequacy
Secondary
Inadequacy
Primary
Inadequacy
Nutrients
reserve
THE PATHOGENESIS OF NUTRITIONAL DEFICIENCY DISEASE
14

Nutrients Reserve Time
Asam amino Bbrp jam
KH 13 jam
Lemak (12% BB) 27 hari
Thiamin 30-60 hari
Ascorbic acid 60-120 hari
Niacin 60-180 hari
Riboflavin 60-180 hari
Vit A 90-365 hari
Iron (menstruating women) 125 hari
Iron (post menopausal women and men) 750 hari
Iodine 2500 hari
ESTIMATION OF SOME NUTRIENTS RESERVE
15

SEVERE PROTEIN ENERGY MALNUTRITION (PEM)
MARASMUS
KWASHIORKOR
19

KWASHIRKOR
MARASMIC-KWASHIORKOR
20

KWASHIORKOR MARASMIC-KWASHIORKOR
21

Oedema in kwashiorkor
 Traditionally considered as direct result of low
albumin and associated with low protein intake
with normal calorie intake
 Inflammation induced by infection is currently
regarded responsible for the oedema via 3
mechanism:
 Transcapillary loss of albumin due to increase
vascular permeability
 Increased albumin catabolism
 Decreased albumin synthesis
22

 Malnutrition without inflammatory state (Non
catabolic state): Low intake due to poverty or
voluntarily (anorexia nervosa, bulimia) 
marasmus type
 Malnutrition with inflammatory state 
kwashiorkor or marasmic-kwashiorkor type
(depending on BW)
 Acute inflammation (high grade inflammation):
Sepsis, Burn, pneumonia, typhoid fever
 Chronic Inflammation (Low grade inflammation):
TB, Liver Cirrhoris, Chronic kidney disease, Cancer,
HIV-AIDS, Colitis. ( 23
Malnutrition

Hospital malnutrition
 Malnutrition characterized by
HYPOALBUMINEMIA is associated with：
 Increased morbidity,
 Increased mortality and
 Prolonged hospital length of stay
24

Types of Malnutrition
• Marasmus
• Kwashiorkor
• Mixed
Because this is a disease with multiple etiologies, the
best terminology would probably be polydeficient
malnutrition.
Green CJ. Clin Nutr 1999;18(s):3-28
26

How common is Malnutrition in surgical patients?
25% of surgical patients are malnourished on admission!
Does it matter?
McWirther, BMJ 1994;308:945-8. Baker, N Engl J Med 1982;306:969-72
0
10
20
30
40
50
60
70
80
Infections (%) LOS (days)
Well
nourished
Moderately
malnourished
Severly
malnourished
P<0.005 (infections)
P<0.0001 (LOS)
27

OBESITY AND IMMUNE FUNCTION
29

Medical Nutrition Therapy
of Diseases
 DDT-----
anthropometrics
 Immunology----allergy &
Food intolerance
 Hematology---
Nutritional related
anemia
 Oncology---dietary
prevention and
management
 Gastroenterology
 Endocrine & Metab:
DM, Thyroid
 Cardiovascular
 Musculoscelteal: Gout
 Neuropsychiatry
 Special sense:
xeropthhlamia
30

Nutrients & Non Nutrients
(Bioactive components)
 Macronutrients: Carbohydrate, Protein, Lipid
 Micronutrients: Mineral, Vitamin
 Phytochemicals (mostly antioxidants):
Carotenoids, Flavonoids, organosulfur,
isothiocyanates, phenolic acids
32

Food utilization by human
body
DIGESTION
ABSORPTION
METABOLISM
EXCRETIONUTILIZATION
FOOD
ALGORITHM OF FOOD UTILIZATION PROCESSES

DIETARY CARBOHYDTARE
LIVER GLICOGEN
BLOOD GLUCOSE
ENERGY
LACTAT ACID
MUSCLE GLICOGEN
PYRUVIC ACID
KREBS CYCLE
CO2 & H2O
ALGORITHM OF CARBOHYDRATE METABOLISM

MAKRONUTRIENTS
DIETARY
CARBOHYDRATES, FAT AND PROTEIN
Dr. Agussalim Bukhari, M.Med.,Ph.D ,Sp.GK
Nutrition Department School of Medicine
Hasanuddin University
@2008
46

DIETARY CARBOHYDRATES
AND FIBRE
47

To see carbohydrate molecular structures go to:
http://www.fao.org/docrep/x5738e/x5738e06.htm
50

INDEKS GLISEMIK (IG)
 Pasien DM dianjurkan untuk mengkonsumsi
makanan dengan IG rendah
 Karbohidrat kompleks/serat tinggi memiliki IG
relatif rendah dibanding Gula sederhana
 IG 70 = tinggi
 IG 56 – 69 = sedang
 IG 55 = Rendah
58

Makanan Tinggi IG menaikkan gula darah
59

60
80
100
120
140
160
0 60 120
BloodGlucose(mg/dL)
Time (min)
Potatoes
Kidney Beans
(GI 75)
(GI 55)
60

60
80
100
120
140
160
180
0 60 120
Bloodglucose(mg/dL)
TIME (min)
Fructose
Sucrose
Glucose
(GI 100)
(GI 70-80)
(GI <50)
61

MAKANAN INDEKS
GLIKEMIK/IG
GLUKOSA
KENTANG
NASI PUTIH
BERAS MERAH
ROTI PUTIH
ROTI TINGGI SERAT
GULA PASIR
MADU
JAGUNG
100
85
80
76
70
69
65
58
55
62

MAKANAN INDEKS
GLIKEMIK/IG
KRIPIK KENTANG
KACANG KEDELE
MIE INSTAN
JUZ JERUK
SPAGHETTI
JUZ APPEL
YOGHURT, RENDAH
LEMAK
SUSU SKIM
KACANG TANAH
54
48
46
46
41
40
33
32
2963

Glycemic Load
66
The glycemic load (GL) of food is a number that
estimates how much the food will raise a person's blood
glucose level after eating it. One unit of glycemic load
approximates the effect of consuming one gram of
glucose.[1] Glycemic load accounts for how much
carbohydrate is in the food and how much each gram of
carbohydrate in the food raises blood glucose levels.
Glycemic load is based on the glycemic index (GI).
Glycemic load is defined as the grams of available
carbohydrate in the food x the food's GI / 100

Glycemic Load
67
Glycemic load estimates the impact of carbohydrate
consumption using the glycemic index while taking into account
the amount of carbohydrate that is consumed. GL is a GI-
weighted measure of carbohydrate content. For instance,
watermelon has a high GI, but a typical serving of watermelon
does not contain much carbohydrate, so the glycemic effect of
eating it (and therefore its GL) is low. Whereas glycemic index is
defined for each type of food, glycemic load can be calculated
for any size serving of a food, an entire meal, or an entire day's
meals.

Glycemic Load
68
GL greater than 20 = high,
GL of 11-19 = medium,
GL of 10 or less = low.
Foods that have a low GL in a typical
serving size almost always have a low GI.
Foods with an intermediate or high GL in a
typical serving size range from a very low to
very high GI.

69
http://www.health.harvard.edu/newsweek/Glyc
emic_index_and_glycemic_load_for_100_foods.
htm

http://en.wikipedia.org/wiki/Dietary_fibre
78

Play a role in blood cholesterol levels. These substances
occur when polyunsaturated oils are altered through
hydrogenation, a process used to harden liquid vegetable oils
into solid foods like margarine and shortening.
One recent study found that trans-monounsaturated fatty
acids raise LDL cholesterol levels, behaving much like
saturated fats.
Simultaneously, the trans-fatty acids reduced HDL
cholesterol readings. Much more research on this subject is
necessary, as studies have not reached consistent and
conclusive findings.
89

Larter, C.Z., Farrel, G.C. 2006. Journal of hepatology. 44 (2): 253-261.

Protein metabolism
 Protein is absorbed in form of amino acid
 Amino acid especially important to build new tissue
or to replace the old one.
 Protein from diet and tissue catabolism form amino
acid pool
 Amino acid from this pool will be burnt as energy in
state of limit source of energy
 Inter-conversion amongst amino acid and catabolic
metabolite from CH and fat takes place through the
process of transamination, deamination, and
amination

Protein metabolism
 Leucine, isoleucine, phenylalanine, and tyrosine
are called ketogenic amino acids since they are
converted to ketone bodies; acetoacetic acid
 Threonine and valine (by irreversible reaction)
and other amino acids (by reversible reaction)
are glucogenic or gluconeogenic

Amino Acid Catabolism: N
Copyright © 1999-2001 by Joyce J. Diwan.
All rights reserved.
Molecular Biochemistry II

Transaminase enzymes (aminotransferases) catalyze
the reversible transfer of an amino group between two
a-keto acids.
H
R1 C COO
-
+ R2 C COO
-
NH3
+
O
Transaminase
H
R1 C COO
-
+ R2 C COO
-
O NH3
+

Example of a Transaminase reaction:
 Aspartate donates its amino group, becoming the
a-keto acid oxaloacetate.
 a-Ketoglutarate accepts the amino group,
becoming the amino acid glutamate.
aspartate a-ketoglutarate oxaloacetate glutamate
Aminotransferase (Transaminase)
COO
CH2
CH2
C
COO
O
COO
CH2
HC
COO
NH3
+
COO
CH2
CH2
HC
COO
NH3
+
COO
CH2
C
COO
O+ +

Transaminase Roles
Transaminases equilibrate amino groups among
available a-keto acids.
This permits synthesis of non-essential amino acids,
using amino groups from other amino acids & carbon
skeletons synthesized in a cell. Thus a balance of
different amino acids is maintained, as proteins of varied
amino acid contents are synthesized.
Although the amino N of one amino acid can be used
to synthesize another amino acid, N must be obtained
in the diet as amino acids (proteins).

Essential Amino Acids
Essential amino acids must be consumed in the diet.
Mammalian cells lack enzymes to synthesize their
carbon skeletons (a-keto acids). These include:
Isoleucine, leucine, & valine
Lysine
Threonine
Tryptophan
Phenylalanine (Tyr can be made from Phe.)
Methionine (Cys can be made from Met.)
Histidine (Essential for infants.)

The prosthetic group of Transaminase is
pyridoxal phosphate (PLP), a derivative of
vitamin B6.
pyridoxal phosphate (PLP)
N
H
C
O
P
O
O
O
OH
CH3
C
H O


H2

In the resting state, the aldehyde group of pyridoxal
phosphate is in a Schiff base linkage to the e-amino
group of an enzyme lysine residue.
N
H
C
O
P
O
O
O
O
CH3
HC


H2
N
(CH2)4
Enz
H
+
R
H
C COO
NH2
Enzyme (Lys)-PLP Schiff base
Amino acid

The a-amino group of a substrate amino acid displaces the enzyme
lysine, to form a Schiff base linkage to PLP.
PLP’s (+) charged N is thought to act acts as an electron sink, to
facilitate catalysis. Lysine extracts H+, promoting tautomerization,
followed by reprotonation & hydrolysis.
N
H
C
O
P
O
O
O
O
CH3
HC


H2
N
H
C
H
+
R COO
EnzLysNH2
Amino acid-PLP Shiff base (aldimine)

What was an amino acid leaves as an a-keto acid.
The amino group remains on what is now pyridoxamine phosphate
(PMP). A different a-keto acid reacts with PMP and the process
reverses, to complete the reaction.
N
H
C
O
P
O
O
O
OH
CH3
CH2
NH2
H2
R C COO
O


EnzLysNH2
Pyridoxamine phosphate (PMP)
a-keto acid

Several other enzymes that catalyze metabolism or
synthesis of amino acids also utilize PLP as prosthetic
group, and have mechanisms involving a Schiff base
linkage of the amino acid to PLP.
N
H
C
O
P
O
O
O
O
CH3
HC


H2
N
H
C
H
+
R COO
EnzLysNH2
Amino acid-PLP Shiff base (aldimine)

Chime Exercise
Each student should pair up with a neighboring student
and each should display as recommended of one of the
following:
 Transaminase with PLP in Schiff base linkage to the
active site lysine residue.
 Transaminase in the PMP form, with glutarate, an
analog of a-ketoglutarate, at the active site.
Students should then show and explain the structure
displayed by them to the neighboring team.

Deamination of Amino Acids
In addition to equilibrating amino groups among
available a-keto acids, transaminases function to funnel
amino groups from excess dietary amino acids to those
amino acids (e.g., glutamate) that can be deaminated.
Carbon skeletons of deaminated amino acids can be
catabolized for energy, or used to synthesize glucose or
fatty acids for energy storage.
Only a few amino acids are deaminated directly.

Glutamate Dehydrogenase catalyzes a major reaction that effects net
removal of N from the amino acid pool.
It is one of the few enzymes that can use NAD+ or NADP+ as e
acceptor. Oxidation at the a-carbon is followed by hydrolysis, releasing
NH4
+.

OOC
H2
C
H2
C C COO
O
+ NH4
+
NAD(P)+
NAD(P)H

OOC
H2
C
H2
C C COO
NH3
+
H
glutamate
a-ketoglutarate
Glutamate Dehydrogenase
H2O

Summarized above: the role of transaminases in
funneling amino N to glutamate, which is deaminated via
Glutamate Dehydrogenase, producing NH4
+.
Amino acid a-ketoglutarate NADH + NH4
+
a-keto acid glutamate NAD
+
+ H2O
Transaminase Glutamate
Dehydrogenase

Some other pathways for deamination of amino acids:
1. Serine Dehydratase catalyzes:
serine  pyruvate + NH4
+
2. Peroxisomal L- and D-amino acid oxidases catalyze:
amino acid + FAD + H2O 
a-keto acid + NH4
+ + FADH2
FADH2 + O2  FAD + H2O2
Catalase catalyzes: 2 H2O2  2 H2O + O2
HO CH2
H
C COO
NH3
+
C COO
OH2O NH4
+
C COO
NH3
+
H2C H3C
H2O
serine aminoacrylate pyruvate
Serine Dehydratase

Most terrestrial land animals convert excess nitrogen to
urea, prior to excreting it. Urea is less toxic than ammonia.
The Urea Cycle occurs mainly in liver.
The 2 nitrogen atoms of urea enter the Urea Cycle as NH3
(produced mainly via Glutamate Dehydrogenase) and as
amino N of aspartate.
The NH3 and HCO3
 (carbonyl C) that will be part of urea
are incorporated first into carbamoyl phosphate.
H2N C
O
NH2
urea

Carbamoyl Phosphate
Synthase (Type I) catalyzes
a 3-step reaction, with
carbonyl phosphate and
carbamate intermediates.
NH3 is the N input.
The reaction, which
involves cleavage of 2 ~P
bonds of ATP, is essentially
irreversible.
H2N C OPO3
2
O
H2N C O
O
HO C
O
OPO3
2
HCO3

ATP
NH3
ADP
ATP
Pi
ADP
carbonyl phosphate
carbamate
carbamoyl phosphate

Alternate forms of
Carbamoyl Phosphate
Synthase (Types II & III)
initially generate ammonia
by hydrolysis of glutamine.
X-ray crystallographic
analysis has shown that the
type II enzyme includes a
long internal tunnel through
which ammonia & reaction
intermediates such as
carbamate pass from one
active site to another.
H2N C OPO3
2
O
H2N C O
O
HO C
O
OPO3
2
HCO3

ATP
NH3
ADP
ATP
Pi
ADP
carbonyl phosphate
carbamate
carbamoyl phosphate

Carbamoyl Phosphate Synthase is the committed step of
the Urea Cycle, and is subject to regulation.
Carbamoyl Phosphate Synthase is allosterically activated
by N-acetylglutamate. This derivative of glutamate is
synthesized when cellular [glutamate] is high, signaling
excess of free amino acids due to protein breakdown or
dietary intake.
H2N C OPO3
2
O
HCO3

+ NH3 + 2 ATP
+ 2 ADP + Pi
Carbamoyl Phosphate
Synthase
carbamoyl phosphate

H2N C OPO3
2
O
CH2
CH2
CH2
HC
COO
NH3
+
NH3
+
CH2
CH2
CH2
HC
COO
NH3
+
NH
CO NH2
COO
CH2
HC
COO
NH2
CH2
CH2
CH2
HC
COO
NH3
+
NH
C NH2
+
COO
CH2
HC
COO
H
N
AMP + PPi
ATP
CH2
CH2
CH2
HC
COO
NH3
+
NH
C
NH2
+
H2N
COO
HC
CH
COO
C NH2H2N
O H2O
Pi
ornithine
urea
citrulline
aspartate
arginino-
succinate
fumarate
arginine
carbamoyl
phosphate
Urea Cycle
1
2
3
4
Urea Cycle
Enzymes in
mitochondria:
1. Ornithine
Trans-
carbamylase
Enzymes in
cytosol:
2. Arginino-
Succinate
Synthase
3. Arginino-
succinase
4. Arginase.

For each cycle, citrulline must leave the mitochondria, and
ornithine must enter the mitochondrial matrix.
Carrier proteins in the inner mitochondrial membrane facilitate
transmembrane fluxes of citrulline & ornithine.
cytosol
mitochondrial matrix
carbamoyl phosphate
Pi
ornithine citrulline
urea aspartate
arginine argininosuccinate
fumarate

Fumarate is converted to oxaloacetate via Krebs Cycle enzymes
Fumarase & Malate Dehydrogenase.
Oxaloacetate is converted to aspartate via transamination (e.g., from
glutamate). Aspartate then reenters Urea Cycle, carrying an amino group
derived from another amino acid.
cytosol
mitochondrial matrix
carbamoyl phosphate
Pi
urea aspartate
arginine argininosuccinate
fumarate
Cytosolic isozymes
of Krebs Cycle
enzymes are
involved in
regenerating
aspartate from
fumarate.

Hyperammonemia Disease
Hereditary deficiency of any of the Urea Cycle
enzymes leads to hyperammonemia - elevated
[ammonia] in blood.
Total lack of any Urea Cycle enzyme is lethal.
Elevated ammonia is toxic, especially to the brain. If
not treated immediately after birth, severe mental
retardation results.
Information about such genetic diseases may be found
in the OMIM (Online Mendelian Inheritance in Man)
web site.

Postulated mechanisms for toxicity of high [ammonia]:
1. High [NH3] would drive Glutamine Synthase:
glutamate + ATP + NH3  glutamine + ADP + Pi
This would deplete glutamate – a neurotransmitter & precursor for
synthesis of the neurotransmitter GABA.
2. Depletion of glutamate & high ammonia level would drive
Glutamate Dehydrogenase reaction to reverse:
glutamate + NAD(P)+  a-ketoglutarate +
NAD(P)H + NH4
+
The resulting depletion of a-ketoglutarate, an essential Krebs Cycle
intermediate, could impair energy metabolism in the brain.

Hyperammonemia Disease
Treatment of deficiency of Urea Cycle enzymes
(depends on which enzyme is deficient):
 limiting protein intake to the amount barely
adequate to supply amino acids for growth, while
adding to the diet the a-keto acid analogs of
essential amino acids.
 Liver transplantation has also been used, since
liver is the organ that carries out Urea Cycle.

Fate of Dietary Protein (amino acids) from one meal
during post-absorptive phase (~2 h)
138

Regulation of Fuel
Utilization

Interrelation amongst Metabolism
of CH, fat, and protein
 Although the the early metabolic process of
those substances are distinct , they will
eventually enters a shared process called
krebs cycle, for oxidative metabolism yielding
a chemical energy (ATP)

Protein
(amino acids)
Carbohydrate
(glucose, fructose, galactose)
Fat
(glycerol, fatty acids)
Intra cells : amino acids
Glucose, glycerol, fatty acid
Excretion:
as feces, urine,
Sweats, lung CO2
Utilization :
Form energy, heat,
enzymes, hormones, growth
Metabolism of carbohydrate, fat, protein

food
CHprotein fat
glucoseglycerolFatty acid
Amino acid
Pyruvic acdAcetoacetic acidGlucogenic AAKetogenic AA
Acetyl CoA
Oxaloacetic acid
Malonyc acidIsocitric acid
Fumarate acid
a- ketoglutarate
acid
succynate acid
Interrelation amongst metabolism of CH, fat, and protein

protein carbohydrate fat
Krebs
cycle
intestine
glucose
G-6-P
glyceraldehide Active
glycerol
Fatty
acids
diglyceride
phospholipid
+ choline
acetoacetate
ketones
cholestrol Bile acid
pyruvate Active acetate
(acetyl CoA)
glycogenPentose
shunt
+
Interrelation amongst metabolism of CH, fat, and protein

The role enzymes in metabolism
 It consists of a protein part synthesized in body
(apoenzyme).
 To activate apoenzyme we need coenzyme (a non-
protein molecule)
 The coenzyme initially inactive and activated by vitamin
B complex
 The bond between apoenzyme and coenzyme is called
holoenzyme.
 Some holoenzymes need minerals to work effectively.

The role enzymes in metabolism
 As every component of the system needed
simultaneously in sufficient amount, that any single
deficiency of those nutrients would interfere with
the entire system.
 Despite one single vitamin only as a component of
one coenzyme, the coenzyme might participate in
other enzymes.
 Therefore, a deficiency in one vitamin could
negatively affect some metabolic pathways
 Refer to the reference handout for more detail

The role of hormones
 Play important roles in coordinating lots of
metabolic process.
 These hormones are created to meet the normal
condition of human being, in both anabolic and
catabolic states.
 For instances : Insulin is an anabolic hormone, while
cortisol is a catabolic
 Growth hormone has a mixed properties; to
synthesize protein by catabolizing Ch and fat
 Refer to the reference handout for more detail

TISSUE-SPECIFIC
METABOLISM
TISSUE FUEL USED FUEL RELEASED
Brain Glucose
Ketone Bodies
Lactate (in prolonged
starvation; the brain can
utilize lactate under some
pathological conditions）
Skeletal Muscle Glucose, FFA, TG, BCAA Lactate, alanine, glutamine
Heart FFA, TG, Ketone bodies,
Glucose, Lactate
Liver Amino acids, FFA, lactate,
glycerol, glucose, alcohol
Glucose, ketone bodies,
lactate, TG
Intestine Glucose, glutamine Lactate, alanine
Red blood cells Glucose lactate
Kidney Glucose, FFA, Ketone
bodies, lactate, glutamine
glucose
Adipose tissue Glucose, TG Lactate, glycerol, FFA 166

/
/
4 8 12 16 20 24 28 2 8 16 24 32 40
/
/
I II III IV V
40
30
20
10
/
/
Hours Days
Exogenous
Gluconeogenesis
GlucoseUsed(g/h)
ORIGIN OF
BLOOD
GLUCOSE
TISSUES
USING
GLUCOSE
MAJOR
FUEL OF
GLUCOSE
:
:
: Exogenous Glycogen, hepatic
gluconeogenesis
Hepatic gluconeo-
genesis, glycogen
Gluconeogenesis
Hepatic and renal
Gluconeogenesis
Hepatic and renal
All
All except liver &
adipose tissue at
diminished rates
All except liver, muscle
& adipose tissue at
rates intermediate
between II & IV
Brain, RBC, Renal
Medulla, small
amount by muscle
Brain, at a diminished
rate, RBC, Renal
Medulla
Glucose Glucose Glucose Glucose, ketone
bodies
Glucose, ketone
bodies
GLUCOSE UTILIZATION VS TIME IN THE 5 PHASES OF GLUCOSE METABOLISM
Glycogen
167

/
/
4 8 12 16 20 24 28 2 8 16 24 32 40
/
/
I II IIIa
40
30
20
10
/
/
Hours Days
Exogenous (dietary glucose)
Gluconeogenesis
GlucoseUsed(g/h)
GLUCOSE UTILIZATION VS TIME IN THE 5 PHASES OF GLUCOSE METABOLISM
Glycogen
I Fed state Most glucose is provided by diet
II Fasted state
(Post absorptive)
Most glucose is provided by breakdown of liver glycogen stores; increasing
amounts are provided by gluconeogenesis
III Starved state Most glucose comes from gluconeogenesis; the breakdown of protein and fat
provides amino acids and glycerol, substrate for gluconeogenesis
total glucose
IIIb

/
/
4 8 12 16 20 24 28 2 8 16 24 32 40
/
/
I II IIIa
40
30
20
10
/
/
Hours Days
Exogenous (dietary glucose)
Gluconeogenesis
GlucoseUsed(g/h)
Glycogen
total glucose
IIIb
State Time course Major fuels used Hormonal control
I. Fed 0-4 h following a meal Most tissues use glucose insulin results in; glucose uptake by peripheral
tissues, glycogen, TG, and protein synthesis
II. Fasted
(post-absorptive)
4-12 h after a meal Brain: glucose
Muscle and liver: fatty acids
glucagon and Noradrenaline stimulate breakdown of
liver glycogen and TG
insulin
IIIa. Early starvation 12h-16 days without food Brain: glucose and some ketone bodies
Liver: fatty acids
Muscle:mainly fatty acids and some ketone bodies
glucagon and NoradrenalineTG hydrolysis and
ketogenesis
cortisolbreakdown of muscle protein, releasing
amino acids for gluconeogenesis
IIIb. Prolonged starvation >16 days without food Brain: uses more ketone bodies and less glucose to preserve body protein
Muscle: only fatty acids
glucagon and Noradrenaline

170
State Time course Major fuels used Hormonal control
I. Fed 0-4 h following a
meal
Most tissues use glucose insulin results in; glucose
uptake by peripheral tissues,
glycogen, TG, and protein
synthesis
II. Fasted
(post-absorptive)
4-12 h after a meal Brain: glucose
Muscle and liver: fatty acids
glucagon and
Noradrenaline stimulate
breakdown of liver glycogen
and TG
insulin
IIIa. Early
starvation
12h-16 days
without food
Brain: glucose and some
ketone bodies
Liver: fatty acids
Muscle:mainly fatty acids and
some ketone bodies
glucagon and
NoradrenalineTG
hydrolysis and ketogenesis
cortisolbreakdown of
muscle protein, releasing
amino acids for
gluconeogenesis
IIIb. Prolonged
starvation
>16 days without
food
Brain: uses more ketone
bodies and less glucose to
preserve body protein
Muscle: only fatty acids
glucagon and
Noradrenaline
Three States of glucose homeostasis

 Fatty acid synthesis: Cytosol (microsome)
 Pyruvate----Acetyl CoA----Malonyl CoA-FFA-
TG
 Fatty acid oxidation: Mitochondria
171

Glucose
90 g
Brain
15-20 g
Liver
20 g
Muscle
20-45 g
Adipose
tissue
2 g
Glycogen
Glycogen ATP
Triacylglycerol
CO2
FATE OF DIETARY CARBOHYDRATE (GLUCOSE) FROM ONE MEAL DURING THE ABSORPTIVE
PHASE (~2 H). GLUCOSE PROVIDES THE GLYCEROL MOETY FOR TRIACYLGLYCEROL SYNTHESIS
20 g25 g
20 g2 g
20 - 45 g
15 - 20 g
172

Plasma concentrations of fuels during prolonged starvation
173

Plasma concentrations of insulin & glucagon during prolonged starvation174

DIETARY VITAMINS
 Dr. Agussalim Bukhari, M.Med.,Ph.D
 Nutrition Department School of Medicine
 Hasanuddin University
 @2008
179

DIETARY MINERALS AND WATER
206

Increase
absorption
Decrease absorption
224

Nutrisi dan Pertumbuhan

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