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Carbohydrate Metabolism

Departme

An Overview of Metabolism

Summary of Metabolism
DIET

Carbohydrates

Fats

Proteins

Lipogenesis

Free fatty acids + glycerol

Fat
stores

Lipogenesis
Excess glucose

Glucose

Glycogenesis

Glycogen
stores
Lipolysis

Urine

Protein
synthesis

Body
protein

Glycogenolysis
Glucose pool

Free fatty
acid pool

Excess nutrients

Amino
acids

Metabolism in
most tissues

Copyright 2007 Pearson Education, Inc., publishing as Benjamin Cummings

Gluconeogenesis
Range of normal
plasma glucose

Amino acid
pool

Brain
metabolism

Figure 22-2

Summary of Metabolism
DIET

Carbohydrates

Fat
stores

Lipogenesis
Excess glucose

Glucose

Glycogenesis

Glycogen
stores
Urine

Glycogenolysis
Glucose pool
Range of normal
plasma glucose

Metabolism in
most tissues
Copyright 2007 Pearson Education, Inc., publishing as Benjamin Cummings

Brain
metabolism

Figure 22-2 (1 of 4)

Metabolism
Summary of biochemical pathways for energy production
Glycogen
Glucose
Glucose 6phosphate
Liver only
G
L
Y
C
O
L
Y
S
I
S

Glycerol

Some
amino
acids

NH3

Cytoplasm

2 ATP

Anaerobic conditions
Pyruvate
Lactate
Aerobic conditions
Pyruvate
CoA

Electron transport
system
O2

Acetyl CoA

Citric
acid
cycle
NH3

ATP + H2O

Copyright 2007 Pearson Education, Inc., publishing as Benjamin Cummings

Mitochondria
Fatty
acids
Ketone
CO2
bodies
(in liver)
2 ATP
Some
amino
acids

Figure 22-3

Metabolism
Push-pull control of metabolism

Copyright 2007 Pearson Education, Inc., publishing as Benjamin Cummings

Figure 22-4

Metabolism

Copyright 2007 Pearson Education, Inc., publishing as Benjamin Cummings

Carbohydrate Metabolism

Primarily glucose

Fruktosa dan galaktosa memasuki jalur-jalur pada


berbagai titik

Semua sel dapat memanfaatkan glukosa


untuk produksi energi
Glukosa serapan dari darah ke sel-sel
biasanya dimediasi oleh insulin dan
transporter
Liver is central site for carbohydrate
metabolism

Glucose uptake independent of insulin

Blood Glucose Homeostasis

Beberapa jenis sel lebih memilih


glukosa sebagai sumber energi (ex.,
CNS)
80-126 mg/dl is normal range of blood
glucose in fasted state
< 200 mg/dl is normal range of blood
glucose in post prandial
Uses of glucose:
Energy source for cells
Muscle glycogen
Fat synthesis if in excess of needs

Fates of Glucose

Fed state

Storage as glycogen

Storage as lipids

Liver
Skeletal muscle
Adipose tissue

Fasted state

Synthesis
Synthesis and
and
breakdown
breakdown occur
occur at
at
all
all times
times
regardless
regardless of
of state...
state...

Metabolized for energy


New glucose synthesized

The
The relative
relative rates
rates of
of
synthesis
synthesis and
and
breakdown
breakdown change
change

High Blood Glucose


Pancreas

Muscle

Insulin:
Glucagon

Glucose absorbed

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 of body regulates which


pathway gets energy

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

Glucose Utilization

Energy
Stores

Pentose
Phosphate
Pathway

Glycolysis

Glucose Utilization

Energy
Stores

Pentose
Phosphate
Pathway

Glycolysis

Glycogenesis

Liver

710% of wet weight


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

Glycogenesis

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 Utilization

Energy
Stores

Pentose
Phosphate
Pathway

Glycolysis

Glycolysis

Urutan reaksi yang mengubah glukosa


menjadi piruvat
Jumlah energi yang dihasilkan relatif kecil
Reaksi glikolisis terjadi dalam sitoplasma
Tidak memerlukan oksigen

Lactate (animals)
Glucose Pyruvate Acetyl-CoA (TCA cycle)
Ethanol (yeast)

Glycolysis

Glucose + 2 ADP + 2 Pi
2 Lactate + 2 ATP + 2 H2O

First Reaction of Glycolysis

Perangkap glukosa dalam sel (ireversibel dalam sel otot)


Heksokinase digunakan oleh sebagian besar tanaman, hewan,
dan mikroba untuk memfosforilasi glukosa
Glukokinase dalam jaringan hati

Glycolysis - Summary
Glucose
2 ATP
4 ADP
2 ADP
4 ATP
2 NAD
2 NADH + H

2 Pyruvate

carbohydrate metabolism

Pyruvate Metabolism

Three fates of pyruvate:

Conversion to lactate (anaerobic)


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

Anaerobic Metabolism
of Pyruvate

Problem:

Selama glikolisis, NADH terbentuk dari NAD +


Tanpa O2, NADH tidak dapat dioksidasi menjadi
NAD +
Tidak ada lagi NAD +
Semua dikonversi menjadi NADH
Tanpa NAD +, glikolisis berhenti ...

Anaerobic Metabolism
of Pyruvate

Solution:

Hidupkan NADH kembali ke NAD + dengan membuat laktat


(reduced)
(oxidized)
(asam laktat)
NADH+H+

NAD+

COO
C

CH3
Pyruvate
(oxidized)

COO
Lactatedehydrogenase

HC

OH

CH3
Lactate

(reduced)

Anaerobic Metabolism
of Pyruvate

ATP yield

Two ATPs (net) are produced


in the anaerobic breakdown of one glucose

The 2 NADHs are used to reduce 2 pyruvate


to 2 lactate

Reaction is fast and doesnt require oxygen

Pyruvate Metabolism Anaerobic


Lactate Dehydrogenase

Pyruvate

Lactate
NADH

NAD+

Laktat dapat diangkut oleh darah ke hati dan


digunakan dalam glukoneogenesis

Cori Cycle

Laktat diubah menjadi


piruvat di hati

Pyruvate Metabolism

Three fates of pyruvate:

Conversion to lactate (anaerobic)


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

Pyruvate metabolism

Convert to alanine and export to blood


Glutamate

Ketoglutarate

COO
C

CH3
Pyruvate

Keto acid

COO
Alanineaminotransferase
(AAT)

HC

NH3+

CH3
Alanine

Amino acid

Pyruvate Metabolism

Three fates of pyruvate:

Conversion to lactate (anaerobic)


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

Glycolysis

Pyruvate Dehydrogenase
Complex (PDH)

Prepares pyruvate to enter the TCA cycle

Aerobic Conditions

Electron
Transport
Chain

TCA Cycle

PDH - Summary
Pyruvate

2 NAD
2 NADH + H
CO2

Acetyl CoA

TCA Cycle
Dalam kondisi aerobik Link siklus TCA piruvat
untuk fosforilasi oksidatif
Terjadi pada mitokondria
Menghasilkan 90% dari energi yang
dilepaskan dari makanan
Metabolizes carbohydrate, protein, and fat
Strateginya adalah untuk mengoksidasi
asetil-KoA menjadi CO2 dan menangkap
energi NADH (FADH2) dan ATP

TCA Cycle - Summary


Acetyl CoA

1 ATP

3 NAD

1 ADP

3 NADH + H

1 FAD
1 FADH2

Oxidative Phosphorylation

Oxidative Phosphorylation
and the Electron Transport
System

Membutuhkan koenzim sebagai


pembawa H+ dan mengkonsumsi
oksigen
Key reactions take place in the electron
transport system (ETS)

Sitokrom dari ETS melewati elektron ke


oksigen, membentuk air

The basic chemical reaction is:


2 H2 + O2 2 H2O

Oxidation and Electron Transport

Oksidasi nutrisi melepaskan energi


yang tersimpan

mendonorkan elektron disertai dengan H +


Electrons transferred to co-substrate
NAD+ + 2H+ + 2eFAD + 2H+ + 2e-

NADH + H+
FADH2

So, What Goes to the ETS???


From each molecule of glucose entering glycolysis:
1.
2.
3.

From glycolysis: 2 NADH


From the TCA preparation step (pyruvate to acetyl-CoA): 2 NADH
From TCA cycle (TCA) : 6 NADH and 2 FADH2

TOTAL: 10 NADH + 2 FADH2

Electron Transport Chain

NADH + H+ and FADH2 enter ETC

Perjalanan melalui kompleks I - IV

H + mengalir melalui ETC dan akhirnya


menempel pada O2 membentuk air
NADH + H+
3 ATP
FADH2
2 ATP

Electron Transport Chain

Glucose Utilization
Adipose

Energy
Stores

Glycogen

Glucose
Pentose
Phosphate
Pathway

Ribose-5-phosphate

Glycolysis

Pyruvate

Pentose Phosphate Pathway

Secondary metabolism of glucose

Produces NADPH

Similar to NADH
Required for fatty acid synthesis

Generates essential pentoses

Ribose
Used for synthesis of nucleic acids

Pentose Phosphate Pathway


Glucose-6phosphate

6-Phosphogluconolactone

6-Phosphogluconate

D-Ribulose5-phosphate

RNA or DNA

D-Ribose5-phosphate

Glucose Utilization
Adipose

Energy
Stores

Glycogen

Glucose
Pentose
Phosphate
Pathway

Ribose-5-phosphate

Glycolysis

Pyruvate

Energy Storage

Energi dari kelebihan karbohidrat (glukosa)


disimpan sebagai lemak dalam jaringan
adiposa
Asetil-KoA (dari siklus TCA) didorong ke
sintesis asam lemak pada saat kelebihan
energi

Ditentukan oleh rasio ATP: ADP

High ATP, acetyl-CoA goes to fatty acid synthesis


Low ATP, acetyl CoA enters TCA cycle to generate
MORE ATP

Fates of Glucose

Fed state

Storage as glycogen

Storage as lipids

Liver
Skeletal muscle
Adipose tissue

Fasted state

Synthesis
Synthesis and
and
breakdown
breakdown occur
occur at
at
all
all times
times
regardless
regardless of
of state...
state...

Metabolized for energy


New glucose synthesized

The
The relative
relative rates
rates of
of
synthesis
synthesis and
and
breakdown
breakdown change
change

Gluconeogenesis

Necessary process

Glucose is an important fuel

Central nervous system


Red blood cells

Not simply a reversal of glycolysis


Insulin and glucagon are primary
regulators

Fasting Situation

Where does required glucose come from?

Glycogenolysis
Kerusakan atau mobilisasi glikogen yang disimpan oleh glukagon
Glukagon - hormon yang disekresi oleh pankreas selama masa puasa

Mobilization of fat stores stimulated by glucagon and epinephrine


Lipolysis
Triglyceride = glycerol + 3 free fatty acids
Glycerol can be used as a glucose precursor

Pemecahan protein otot dengan pelepasan asam amino


Proteolysis
Alanin dapat digunakan sebagai prekursor glukosa

Low Blood Glucose


Pancreas

Muscle

Insulin:
Glucagon

Proteins Broken Down

Glycogen
Glucose released

Adipose
Cells
Glycerol, fatty acids released

Dalam keadaan berpuasa, substrat untuk sintesis glukosa


(glukoneogenesis) dilepaskan dari "penyimpanan" ...

Fasted-State Metabolism
FASTED-STATE METABOLISM
Liver glycogen becomes glucose.
Liver
glycogen
stores
Glycogenolysis
Energy
production

Energy production

Glucose

Glycogen
Gluconeogenesis

Pyruvate
or
Lactate

Glucose

Energy production

Copyright 2007 Pearson Education, Inc., publishing as Benjamin Cummings

Figure 22-7 (2 of 5)

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

Terjadi terutama dalam hati, tetapi juga dapat


terjadi pada ginjal dan usus halus

Fasted-State Metabolism
Adipose lipids
become free
fatty acids and
glycerol that
enter blood.

FASTED-STATE METABOLISM
Liver glycogen becomes glucose.
Liver
glycogen
stores
Glycogenolysis
Energy
production

Glucose

Free fatty
acids

-oxidation

Triglyceride stores

Free fatty
Glycerol
acids
Gluconeogenesis

Ketone
bodies

Energy production
Glycogen
Gluconeogenesis

Proteins

Pyruvate
or
Lactate

Glucose

Ketone
bodies

Energy production
Brain can
use only glucose
and ketones for energy.

Copyright 2007 Pearson Education, Inc., publishing as Benjamin Cummings

Amino
acids

Muscle glycogen can be used for energy.


Muscles also use fatty acids and break
down their proteins to amino acids that
enter the blood.

Figure 22-7

Fasted-State Metabolism
FASTED-STATE METABOLISM
Liver glycogen becomes glucose.
Liver
glycogen
stores
Glycogenolysis
Energy
production

Glucose

Glucose

Energy production

Copyright 2007 Pearson Education, Inc., publishing as Benjamin Cummings

Figure 22-7 (1 of 5)

Fasted-State Metabolism
FASTED-STATE METABOLISM
Liver glycogen becomes glucose.
Liver
glycogen
stores
Glycogenolysis
Energy
production

Energy production

Glucose

Glycogen
Gluconeogenesis

Proteins

Pyruvate
or
Lactate

Glucose

Amino
acids

Energy production

Copyright 2007 Pearson Education, Inc., publishing as Benjamin Cummings

Figure 22-7 (3 of 5)

Fasted-State Metabolism
Adipose lipids
become free
fatty acids and
glycerol that
enter blood.

FASTED-STATE METABOLISM
Liver glycogen becomes glucose.
Liver
glycogen
stores

Free fatty
acids

Glycogenolysis
Energy
production

Triglyceride stores

Free fatty
Glycerol
acids
Gluconeogenesis
Energy production

Glucose

Glycogen
Gluconeogenesis

Proteins

Pyruvate
or
Lactate

Glucose

Energy production

Copyright 2007 Pearson Education, Inc., publishing as Benjamin Cummings

Amino
acids

Muscle glycogen can be used for energy.


Muscles also use fatty acids and break
down their proteins to amino acids that
enter the blood.

Figure 22-7 (4 of 5)

Fasted-State Metabolism
Adipose lipids
become free
fatty acids and
glycerol that
enter blood.

FASTED-STATE METABOLISM
Liver glycogen becomes glucose.
Liver
glycogen
stores
Glycogenolysis
Energy
production

Glucose

Free fatty
acids

-oxidation

Triglyceride stores

Free fatty
Glycerol
acids
Gluconeogenesis

Ketone
bodies

Energy production
Glycogen
Gluconeogenesis

Proteins

Pyruvate
or
Lactate

Glucose

Ketone
bodies

Energy production
Brain can
use only glucose
and ketones for energy.

Copyright 2007 Pearson Education, Inc., publishing as Benjamin Cummings

Amino
acids

Muscle glycogen can be used for energy.


Muscles also use fatty acids and break
down their proteins to amino acids that
enter the blood.

Figure 22-7 (5 of 5)

K ETO G EN ESIS

Ketogenesis adalah proses


dimana BADAN KETON atau
senyawa yang dihasilkan
dari molekul asetil CoA
sebagai hasil dari degradasi
asam lemak.

Ketogenesis and Ketone Bodies


In ketogenesis:

Lemak tubuh terurai


untuk memenuhi
kebutuhan energi.
Senyawa Keto yang
disebut bentuk
badan keton.
72

Ketogenesis and Ketone Bodies


In ketogenesis:
Sejumlah besar asetil KoA menumpuk.
Dua molekul asetil KoA bergabung membentuk
asetoasetil KoA
Asetoasetil KoA menghidrolisis untuk asetoasetat, tubuh
keton.
Asetoasetat tereduksi menjadi -hydroxybutyrate atau
kehilangan CO2 untuk membentuk aseton, kedua badan
keton.
73

Reactions of Ketogenesis

Ketone bodies

74

K ETO G EN ESIS
Badan keton diproduksi terutama di

mitokondria hepatosit.
Sintesis terjadi sebagai respons terhadap
kadar glukosa rendah dalam darah, dan
setelah kehabisan simpanan karbohidrat
seluler, seperti glikogen.
Produksi badan keton kemudian
berinisiatif untuk membuat energi
tersedia yang disimpan sebagai asam
lemak.

K ETO G EN ESIS
Namun, jika jumlah asetil-KoA yang

dihasilkan dalam fatty-acid -oxidation


menentang kapasitas pengolahan dari
siklus TCA atau jika aktivitas dalam
siklus TCA rendah karena jumlah
rendah intermediet seperti
oksaloasetat, acetyl-CoA kemudian
digunakan sebagai pengganti dalam
biosintesis badan keton melalui

K ETO G EN ESIS
REVIEW!
Asam lemak menjalani

-oxidation to form
acetyl-CoA.
Biasanya, asetil-CoA

selanjutnya teroksidasi
dan energinya ditransfer
sebagai elektron untuk
NADH, FADH2, dan GTP
dalam siklus Krebs.

K ETO G EN ESIS

K ETO G EN ESIS
The three ketone bodies are:
Acetoacetate - if not oxidized to form usable

energy, it is the source of the two other ketone


bodies below.
Acetone - is not used as an energy source, but
is instead exhaled or excreted as waste.
-hydroxybutyrate - it is not technically a
ketone according to IUPAC nomenclature.
Each of these compounds are synthesized from

acetyl-CoA molecules.

K ETO G EN ESIS
Ketogenesis mungkin atau tidak mungkin

terjadi, tergantung pada tingkat


karbohidrat yang tersedia di sel atau
tubuh.
When the body has ample carbohydrates

available as energy source, glucose is


completely oxidized to CO2.
When the body has excess carbohydrates
available, some glucose is fully metabolized,
and some of it is stored by using acetyl-CoA to
create fatty acids.

K ETO G EN ESIS
Ketika tubuh tidak memiliki karbohidrat bebas

yang tersedia, lemak harus dipecah menjadi


asetil-KoA untuk mendapatkan energi. AsetilKoA tidak didaur ulang melalui siklus asam
sitrat karena intermediet siklus asam sitrat
(terutama oksaloasetat) telah habis untuk
memberi makan jalur glukoneogenesis, dan
akumulasi dihasilkan asetil-CoA mengaktifkan
ketogenesis.
Ketogenesis menyediakan energi untuk fungsifungsi organ vital 'selama kelaparan yang
berkepanjangan

K ETO G EN ESIS

K ETO G EN ESIS

K ETO G EN ESIS
Badan keton dibuat pada tingkat moderat

dalam tubuh kita, seperti saat tidur dan


waktu lain bila tidak ada karbohidrat yang
tersedia.
Namun, ketika ketogenesis yang terjadi
lebih tinggi dari tingkat normal, tubuh
dikatakan dalam keadaan ketosis. Badan
keton terakumulasi dalam tubuh dapat
menyebabkan efek negatif jangka
panjang.

K ETO G EN ESIS
Konsentrasi tinggi abnormal badan keton

pada tubuh menghasilkan penurunan


tingkat pH darah. kondisi ini disebut
ketoasidosis.
Ketoasidosis sangat jarang terjadi. Hal ini,
bagaimanapun, lebih terlihat pada orang
yang menderita Diabetes mellitus (DM)
dan pada mereka pecandu alkohol setelah
pesta minuman keras dan kelaparan
berikutnya.

D iabetes and K etoacidosis


Bila tidak ada cukup insulin dalam darah,

glukosa tidak digunakan secara efisien untuk


menghasilkan energi. Dengan demikian,
tubuh harus memecah lipid untuk energi.
Degradasi lipid menyebabkan keton
menambah dalam darah. Keton kemudian
meluas ke urin sehingga tubuh bisa
menyingkirkan mereka. Aseton dapat
dihembuskan melalui paru-paru. Keton yang
membangun di dalam tubuh untuk waktu
yang lama menyebabkan penyakit serius dan
koma. (Ketoasidosis diabetik)

Ketosis
Ketosis occurs:
In diabetes, diets high in
fat, and starvation.
As ketone bodies
accumulate.
When acidic ketone
bodies lowers blood pH
below 7.4 (acidosis).

87

Ketone Bodies and Diabetes

The blood glucose is elevated within


30 min following a meal containing
carbohydrates
The elevated level of glucose
stimulates the secretion of insulin,
which increases the flow of glucose
into muscle and adipose tissue for
synthesis of glycogen (+ stimulates
glycolysis)
As blood glucose levels drop, the
secretion of glucagon increases,
which stimulates the breakdown of
glycogen in the liver to yield
glucose
88

Ketone Bodies and Diabetes


In diabetes:

Insulin does not function properly.

Glucose levels in muscle, liver, and adipose


tissue are insufficient for energy needs.

As a result, liver cells synthesize


glucose from non-carbohydrate
sources (gluconeogenesis) and fats are broken
down to acetyl CoA.

The level of acetyl CoA is elevated.

Excess acetyl CoA undergoes ketogenesis.

Ketogenesis produces ketone bodies.

Ketone bodies accumulate in the blood.

89