Basic Metabolism of

Carbohydrate, Fat and Protein

Sarwono Waspadji
Jakarta Diabetes & Lipid Center
Division of Endocrinology & Metabolism,
Department of Medicine, School of Medicine
University of Indonesia, Jakarta

Fed

Starvation

Diet/Food

none

Insulin

+
Vital organs

CHO and Lipid

Stores

Insulin

Vital organs

CHO and Lipid

Stores

Counter Insulin Hormone

glucagon
catecholamines
growth hormone (Adipose)
glucocorticoids

Glucose provides a major energy

supply
primary source for brain, adrenal medulla
sole provider for RBCs, retina
Intricate, delicate, well coordinated mechanism to
maintain ECF glucose within narrow range
Glygenolysis, Gluconeogenesis in the liver
Gluconeogenesis in the kidney
Glucose clearance by skeletal muscle,
adipose tissue splanchic bed, liver

The Five Phases of Fuel Homeostasis

Glucose Used g/h

II

III

IV

40

Exogenous
30

20

10

Origin of
Glucose

Glycogen

12

16

Hours

Exogen Glycogen
Hepatic Gluconeogenesis

Tissue using All

Glucose
Major Fuel
of Brain

// Gluconeogenesis

All except Liver

Muscle and
Adipose Tisue at
diminIshed rate
Glucose Glucose

20

24

28

Hepatic Gluconeogenesis
Glycogen

//

16

Days

Gluconeogenesis
Hepatic and Renal

24

32

40

Gluconeogenesis
Hepatic and Rena

Brain, RBCs, Renal Med. Brain, at a

All except Liver
Small amount by muscle Diminished rate,
Muscle and Adipose
RBCs,Renal Med.
Tisue at rates in intermediate between II and IV
Glucose
Glucose, Ketone bodies
Ketone Bodies
Glucose

Risk of Malnutrition - Hospital Cos

Risk of malnutrition
30,000

No Risk of malnutrition

26,359

25,000
18,898

Cost per
Patients
(US $)

20,000
15,000

11,174

10,000

7902

5000

6,858
4979

Pneumonia

Intestinal Surgery

Complications

Reilly et al. JPEN 1988

Number of Complications

Nutrition Therapy Affects Outcomes:

Fewer Complications
With nutrition therapy
15

1st hospitalization

Without nutrition therapy

2nd hospitalization
At 6 months
10

0
n=28n=32

n=9n=15

n=25n=27

n= number of hip fracture patients

Delmi M et al. Lancet 1990

PROSES NUTRISI
Vit, mineral, Air
Vit, mineral, Air

Monosakarida
Asam amino
Asam lemak, monogliserida

CHO, PROTEIN,LIPID
Makanan dalam bentuk
molekul kompleks

Pencernaan
makanan

Lambung
Pankreas
Hati,empedu

Penyerapan makanan
dalam bentuk
molekul sederhana

Pembuangan
makanan

usus halus

Distribusi

Enersi

feses / tinja

Metabolisme

Sel

Aliran darah

Sintesis protein
tubuh dan sel-sel lain

NUTRISI PARENTERAL

NUTRISI ORAL
Protein
Karbohidrat
Lemak
Vitamin
Mineral
Air

Asam Amino
Monosakarida
Lemak
Vitamin
Mineral
Air

Pencernaan makanan
Asam Amino
Monosakarida
Lemak
Vitamin
Mineral
Air

ALIRAN
DARAH
Metabolisme Selular

Karbohidrat :
Monosakarida : glukosa, fruktosa,
galaktosa, ribosa
Disakarida : sukrosa, laktosa,
maltosa
Polisakarida : Pati (tepung),
selulosa, glikogen

Pencernaan Karbohidrat
AMILUM
Ptialin (air liur)
Amilase Pankreas

Laktosa
Laktase
Usus Halus

Galaktosa

Maltosa
Maltase
Dekstrinase
Usus Halus

Glukosa

Sukrosa
Sukrase
Usus Halus

Fruktosa

METABOLISME KARBOHIDRAT
Karbohidrat/
polisakarida

glycogenesis
Glycogen glycogenolysis

monosakarida
lactate
glukoneogenesis/

Glucose
Glucolysis gluconeogenesis
Acetyl CoA
Pyruvate

Oxaloacetate
Fumarate

Citrate

Citric acid cycle

Succinate

Ketoglutarate

Karbohidrat/
polisakarida

METABOLISME KARBOHIDRAT
maltose
Sumber KH Lain
ensim pencernaan

monosakarida
Glycogen
HMP-shunt

ribose-PO 4

Glucose

xylitol

D-xylulose

fructose-1-PO 4

Acetyl CoA

Pyruvate
fructose

sorbitol

Oxaloacetate

Fumarate

Succinate

Citrate

Citric acid cycle

Ketoglutarate

Minimum requirement of CHO 50 g/day

Very low CHO intake will cause gluconeogenesis

For gluconeogenesis, larger amount of metab. water
more water excreted,
relative dehydration
High CHO intake increased CHO oxidation and
glycogen storage
Glucose in parenteral sol. has similar fate with CHO
Lipogenesis tend to occur in high consumption of
sucrose and fructose
Fructose is readily metabolized and converted into
intermediary metabolite (pyruvate) which then can be
oxydized or in larger amount can be converted to
acetyl Co-A and then FFA, therefore increase
circulating TG levels

Hibiscus rosacinensis

PROTEIN
1. Protein Sederhana
Hanya terdiri dari polipeptida
2. Protein Kompleks
Glikoprotein, Lipoprotein, Nukleoprotein

Protein = zat pembangun tubuh

Tidak dapat disimpan seperti CHO / Fat

PROTEIN
Terdapat di tubuh sebagai aktin & miosin di otot; sebagai antibodi,

kolagen di kulit,tulang dan sendi, sebagai ensim, hemoglobin di

darah, keratin di rambut dan kuku, reseptor membran dan hormon
Bermacam-macam protein terbentuk dari 20 macam asam amino
Setiap asam amino terdiri dari : atom karbon (alpha carbon) yang
mengandung 1 atom hidrogen (H), 1 grup amino (NH 2), 1 grup
karboksil (COOH) dan 1 grup R (Alkil) yang menjadi identitas asam
amino tersebut.

NH2

R - C COOH
H
Asam amino terikat satu-sama lain dengan ikatan peptide
Satu protein terdiri dari rantai polipeptide panjang yang terdiri
dari 60-6000 asam amino

ASAM AMINO

Jenis asam amino dibedakan dari grup R-nya :

- dengan grup R basic : Lysine, Arginine, Histidine

- dengan grup R acidic : Aspartic acid, Glutamic acid
- dengan grup R neutral, polar : Glycine, Serine, Threonine,
Cysteine, Tyrosine, Asparagine, Glutamine
- dengan grup R hidrophobic : Alanine, Proline,
Phenylalanine,
Tryptophan, Methionine
- dengan rantai cabang : Valine, Leucine, Isoleucine
Asam amino esensial : Tryptophan, Phenylalanine, Isoleucine,
Leucine, Valine, Methionine, Threonine, Lysine
Pada bayi baru lahir, Histidine, Tyrosine dan Cysteine juga esensial karena

bayi belum punya ensim untuk menyintesis

Pada pasien uraemia, Histidine juga esensial
Pada orang dewasa, Histidine semi esensial karena diperlukan jumlah besar
untuk sintesis protein dan pertumbuhan

Pencernaan Protein
PROTEIN
Pepsin

Proteosa, Pepton, Polipeptida

Tripsin, Kemotripsin
Karboksipeptidase
Polipeptida

Peptidase
Asam amino

Asam Amino

METABOLISME PROTEIN

Alanine,
serine,
glycine
cysteine
threonine
aspartate,
asparagine
tyrosine,
phenylalanine

isoleucine,
valine,
methionine
Protein

asam amino

leucine, lysine,
tyrosine, tryptophan,
phenylalanine
arginine,
glutamine,
proline histidine
glutamate

METABOLISME PROTEIN
Sintesis protein
untuk pembangun
tubuh
Alanine,
serine,
glycine
cysteine
threonine
aspartate,
asparagine
tyrosine,
phenylalanine

asam amino akan dibakar

bila :
sintesis sudah sampai batas
maksimal
bila sumber enersi lain
kurang jumlahnya
bila utilisasi karbohidrat
terganggu karena penyakit
(a.l. sepsis, trauma)

leucine, lysine,
tyrosine, tryptophan,
phenylalanine

arginine,
glutamine,
proline

histidine

glutamate
isoleucine,
valine,
methionine

Protein

asam amino

METABOLISME PROTEIN
citric acid cycle
rangka karbon
Alanine,
serine,
glycine

urea lewat urin

urea cycle
ammonia

transaminase/deaminase

cysteine
threonine
aspartate,
asparagine
tyrosine,
phenylalanine

leucine, lysine,
tyrosine, tryptophan,
phenylalanine

arginine,
glutamine,
proline

histidine

glutamate
isoleucine,
valine,
methionine

Protein

asam amino
Transaminasi Ketoanalog/Ketoacids pada CKD

METABOLISME PROTEIN

glukoneogenesis/
alanine cycle
Alanine,
serine,
glycine

Acetyl CoA

Pyruvate

ketone bodies

cysteine
threonine

Oxaloacetate

Citrate

aspartate,
asparagine
tyrosine,
phenylalanine

Fumarate

Succinate
isoleucine,
valine,
methionine

Protein

asam amino

Citric acid cycle

Ketoglutarate

leucine, lysine,
tyrosine, tryptophan,
phenylalanine

arginine,
glutamine,
proline

histidine

glutamate

After a high protein diet:Protein can not be stored

Insulin release : uptake of BCAA into muscle
Glucagon release: increase gluconeogenesis
Excessive animal protein intake:
increase urinary calcium
increase uric acid
Kidney stones
oxalate excretion
BCAA provide 30% of energy requirement for skeletal muscle,
heart and brain when gluconeogenesis and ketogenesis are
depressed (such in severe Liver disease)

In End Stage Liver disease BCAAs decrease

AAAs increase

Lipids
Simple Lipids
Fatty Acids - Saturated, Unsaturated - Mono-Poly
Cholesterol
Sphingosine

Complex Lipids: Cholesteryl Esters

Triglycerides (Triacylglycerol)
Phosphatidylcholine (Lecithin)
Phosphatidylethanolamine (Cephalin)
Sphingomyelin

Metabolic Intermediates: Phospholipids

(Monoacylglycerol, Diacylglycerol,
Lyophosphatydilcholine, ceramide etc.)

Essential Fatty Acid:

Linoleic Acid and Linolenic acid

Essential for Phospholipid and Eikosanoid

Gejala defisiensi dermatitis, lambatnya penyembuhan luka

dan pertumbuhan, karena adanya cacat pada fungsi membran sel.

Role of Lipids

Cholesterol
Synthesis of plasma membrane
Synthesis of streroid hormones, vit D
Synthesis of bile acids
Triglyceride
Major source of energy

Fatty Acids
Energy
Growth Requirement
Precursors to or modulators of bioregulators
-Prostaglandin etc.

Lipid: pelarut vitamin A, D, E, K

Lipid Biosynthesis
Lipogenesis: - Synthesis of

fatty acids from glucose.

Fatty acids is then incorporated into

VLDL, hydrolize - FFA

Glycerol lipids:

TG, secreted as

MonoAcylGlycerol, DAG

Low FA DAG is converted to Phosphatidylcholine

or to Phosphatidylethanolamine
High FA DAG is converted to TG

Cholesterol: acetyl-coA, Acetoacetyl-coA, HMG-coA,

Farnesylpyrophosphate,

Mevalonate,

Squalene, Lanosterol, Cholesterol

Sphingolipids: important comp. of plasma membrane

Pencernaan Lemak
LEMAK

Empedu
Lemak Yang teremulsi

Lipase pankreas
Asam Lemak

Trigliserida

Monogliserida

Gliserol

Asam Lemak

Atherogenic and antiatherogenic lipoproteins

Bile Acid

From the liver

LDL Receptor

Back to the liver

Reverse cholesterol
transport

Endogenous Pathway

TG
C

TG
apoB

VLDL

C
apoB

IDL

C
C

apoB

large
buoyant

small
dense

LDL

LDL

At h e r o g e n i c

apo A-I

HDL
Anti-atherogenic
Future Forum
DEFINING GLOBAL STANDARDS IN VASCULAR DISEASE

Reverse Cholesterol Transport

Cell
membrane

Liver

SRB1

CE

BA
Bile

CE

CE
ABCA1

FC
LCAT
HDL

CETP
HDL3

LDL
receptor

(Intestine)

VLDL, IDL, LDL

TG

Peripheral
tissues
Free cholesterol
FC
TG
Triglycerides
CE
Cholesteryl esters
LCAT Lecithin cholesterol acyltransferase
CETP Cholesteryl ester transfer protein

METABOLISME LEMAK

Lemak
asam lemak
monogliserida

transport lemak

lemak

glycerol

asam lemak

glukoneogenesis
oksidasi beta
Acetyl CoA

Pyruvate

ketogenesis
ketone bodies

Oxaloacetate

Fumarate

Citrate

Citric acid
cycle

Succinate

PENGGUNAAN LEMAK DI HATI

ASAM LEMAK DI HATI

Ketoglutarate

OKSIDASI

CO2+ H2O

OKSIDASI

Acetyl CoA

Sintesis VLDL trigliserida

Ketone bodies

High-fat content food (40% of calories)

suppress de novo lipogenesis
Excess fat is efficiently stored in adipose tissue

High SaturatedFAs: might cause hypercholesterolemia

Medium Chain FAs and Short ChainFAs:
can pass directly into portal vein and tranported to the liver, wherein,
they diffuse into mitochondria without the aids of Carnitine, and can be
used as readily available source of calories, Not stored in adipose
and do not cause hyperlipidemia.

They are rapidly oxidized and are more ketogenic

PUFA:
undergo oxidation rather different from SFAs (Modified Ox)
Energy yield from PUFAs is less than from SFAs
Can be converted to Eicosanoids and for component
of phospholipids

Hubungan antara Metabolisme KH, Protein dan lemak

Ketiganya dapat dipakai untuk menghasilkan

energi
Ketiganya melalui proses yang sama TCA
untuk oksidasi menjadi CO2 +H2O
Banyak cara untuk konversi di antara ketiganya

Karbohidrat/
Polisakarida

Asam Lemak

Monosakarida

Glycerol

Glukosa

Laktat
Alanine,
serine,
glycine

Monogliserida

Lemak

Glikogen

Lemak

Asam Lemak

Acetyl CoA

Pyruvate

ketone bodies

cysteine
threonine

Oxaloacetate

Citrate

aspartate,
asparagine
tyrosine,
phenylalanine

Fumarate

Succinate

Citric acid cycle

Ketoglutarate

leucine, lysine,
tyrosine, tryptophan,
phenylalanine

arginine,
glutamine,
proline

histidine

glutamate

isoleucine,
valine,
methionine

Protein

asam amino

Hubungan Metabolisme KH, Protein, dan Lemak

Thank You