PENGATURANNYA
1,2
Marhaen Hardjo
1
Head of Biochemistry Department, Medical Faculty of Hasanuddin University
2
Director of Stem Cell Center Hasanuddin University Hospital
DEPARTMENT OF BIOCHEMISTRYY
MEDICAL FACULTI OF
HASANUDDIN UNIVERSITY
KERANGKA SLIDE
Metabolisme
ANABOLISME KATABOLISME
Glukosa Glikogen
Glikogen Glukosa
The main
source of
energy
Fats Protein
Pengertian interelasi
metabolisme
UNTUK SEL
M’bntuk molekul baru
Mngganti struktur sel yg rusak
Mengeluarkan dan memasukkan zat-zat dari dan kedalam sel
Membentuk molekul cadangan energi
• Tidur
2 Aktifitas fisik (AF)
Nilai TEF biasa disebut juga dengan Specifik Dinamik Action= SDA. Nilai TEF
untuk protein adalah tertinggi 30 %, lalu karbohidrat, kemudian lemak. SDA
bekerja mulai dari TEF tertinggi kemudian yang terendah. Karena menu
makanan merupakan gabungan protein, karbohidrat dan lemak, maka nilai TEF
adalah 10 % dari ( BEE + AF )
• CONTOH PERHITUNGAN ENERGI UNTUK PA’ RAHMAT YANG BERUMUR 30 TAHUN, BB=60
KG DAN TB=160 CM, AKTIFITAS SEHARI-HARINYA DIKATEGORIKAN SEDANG (50%). BEE
(CARA DU BOIS) BEE PRIA = 66 + (13.7 X BB KG ) + ( 5 X TB CM ) – ( 6,8 X U.THN ) =
1450 KKAL
•Primarily depends
on boxidation of
fatty acids for its
own energy needs.
Liver
•Amino acids go directly
to the liver through the
portal vein after
absorption.
•Uses them to make
proteins, for
gluconeogenesis, for
biosynthesis of nitrogen
containing molecules, or
for fuel.
Adipose Tissue maintainer #2
•Stores triglycerides and releases FA’s
and glycerol as signaled by glucagon/
epinephrine
•Turnover is 5060 g/day.
cAMPactivated
triglycerides fatty acids + glycerol
lipases
transport in blood
Albumin
(Phosphagen system)
Match the photo to the energy system!
a) 1= lactate; 2= phosphagen; 3= aerobic
b) 1= phosphagen; 2= aerobic; 3= lactate
c) 1= aerobic; 2= lactate; 3= phosphagen
d) 1= aerobic; 2= phosphagen; 3= lactate
1. 2. 3.
Anaerobic Conditions- bursts
of heavy activity
• ATP exhausted rapidly (1 or 2 sec); replenished by:
Phosphagen System
Anaerobic Conditions- bursts
of heavy activity
•phosphocreatine lasts ~10 seconds
•next 1 to 2 minutes
glycogen > G6P > pyruvate > lactate
Fate of Lactate
•Cooperation
between muscle and
liver (Cori cycle) to
regenerate glucose
from lactate.
•Heart also burns
lactate.
Lactate Threshold
• WITH LOW INTENSITY WORK, LACTATE IS CLEARED FROM THE
BLOODSTREAM AS FAST AS IT IS MADE.
• AS WORK INCREASES, THERE IS A POINT WHEN LACTATE IS
PRODUCED TOO FAST FOR THE BODY TO CLEAR IT.
Exercise cannot be
sustained for more
than a minute or two
after lactate threshold
because of PFK-1
inhibition
work
Aerobic Conditions- rest,
slow runs, light activity
1. glycogen > G6P > pyruvate > CO2 + H2O
•1 2 hour supply, moderately fast
•Limited by entry of pyruvate into mitochondria
and/or O2 supply
2. fatty acids > acetylCoA > CO2 + H2O
•Many hours supply, slow
•Limited by diffusion of FA’s from blood, carnitine
Cross Country Collapse
PRONGHORN ANTELOPE
300 ML/KG/MIN
10K- UNDER 10 MINUTES!
Changes in metabolism
over time
During endurance exercise, the
respiratory quotient (CO2 exhaled/O2
consumed) falls, indicating increased use
of fatty acids.
•Dependent on blood glucose at ~4.5 mM to
maintain ion gradients.
•Uses 20% of the total O2 consumed by a resting
human (only 2% of the body mass)
•After several days of low glucose, switches to
use of ketone bodies, which are degraded via
TCA. Conserves body’s proteins.
Heart
Cardiac muscle is
aerobic only with
circulating fats the
preferred fuel.
Lack of O2 leads to
tissue death (myocardial
infarction).
Hormones
WHICH OF THE FOLLOWING PATHWAYS IS
INHIBITED BY THE
A. GLYCOLYSISACTION OF INSULIN?
B. KREB’S CYCLE
C. GLUCONEOGENESIS
D. GLYCOGEN SYNTHESIS
Urea
Glycogen
nonreducing reducing
end end
The figures were found (May 2007) at http://www.wellesley.edu/Chemistry/chem227/sugars/oligo/glycogen.jpg
http://students.ou.edu/R/Ben.A.Rodriguez1/glycogen.gif, http://fig.cox.miami.edu/~cmallery/255/255chem/mcb2.10.triacylglycerol.jpg
INTERMEDIARY METABOLISM
RELATIONSHIPS
(SACCHARIDES, LIPIDS,
2. DURING FASTING
PROTEINS)
USE OF ENERGY STORES
• GLYCOGEN → GLUCOSE
• TAG → FATTY ACIDS
• GLYCOGENESIS • GLYCOGENOLYSIS
• GLUCONEOGENESIS • GLYCOLYSIS
• LIPOGENESIS • LIPOLYSIS
• SYNTHESIS OF FA • b-OXIDATION
• KETOGENESIS • KETONE BODIES DEGR.
• PROTEOSYNTHESIS • PROTEOLYSIS
• UREA SYNTHESIS • DEGRADATION OF AA
ACETYL-CO A
PYRUVATE
NADH
PYRUVATE (PDH) – I.E. FROM GLUCOSE
AMINO ACIDS (DEGRAD.) – FROM PROTEINS
FATTY ACIDS (b-OXIDATION) – FROM TAG
KETONE BODIES (DEGRAD.) – FROM FA
ACETYL-COA
PYRUVATE
ACETYL-COA (PDH)
LACTATE (LACTATE DEHYDROGENASE)
ALANINE (ALANINE AMINOTRANSFERASE)
OXALOACETATE (PYRUVATE CARBOXYLASE)
GLUCOSE (GLUCONEOGENESIS)
AEROBIC GLYCOLYSIS
PDH REACTION
b-OXIDATION
CITRATE CYCLE
OXIDATION OF ETHANOL
NADH
WHERE?
WHEN?
HOW?
COMPARTMENTALIZATION OF THE
PATHWAYS
STARVE-FEED CYCLE
REGULATION OF THE PROCESSES
COMPARTMENTALIZATION OF MTB
PATHWAYS
The figure is found at http://fig.cox.miami.edu/~cmallery/150/proceuc/c7x7metazoan.jpg (May 2007)
• GLYCOLYSIS
• GLUCONEOGENESIS (FROM OXALOACETATE
OR GLYCEROL)
• METABOLISM OF GLYCOGEN
• PENTOSE CYCLE
• SYNTHESIS OF FATTY ACIDS
• SYNTHESIS OF NONESSENTIAL AMINO
ACIDS
• TRANSAMINATION REACTIONS
• SYNTHESIS OF UREA (A PART; ONLY IN THE
LIVER!)
ROUGH ER
• PROTEOSYNTHESIS
• POSTTRANSLATIONAL MODIFICATION OF
PROTEINS
• PROTEIN SORTING
• EXPORT OF PROTEINS (FORMATION OF
VESICULES)
RIBOSOMES
• PROTEOSYNTHESIS
NUCLEUS
• HYDROLYSIS OF PROTEINS,
SACCHARIDES, LIPIDS AND NUCLEIC
ACIDS
PEROXISOMES
The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed.
Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2
2) Early
fasting state
The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed.
Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2
3) Fasting
state
The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed.
Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2
4) Early
refed state
The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed.
Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2
The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed.
Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2
CHANGES OF LIVER GLYCOGEN
CONTENT
The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed.
Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2
FASTING
WELL-FED STATE
STATE
glucagon,
hormones insulin
adrenaline, cortisol
glycemia
glycemia
response of lipolysis
lipogenesis
the body ketogenesis
proteosynthesis
proteolysis
FASTING
WELL-FED STATE
STATE
glucagon,
hormones insulin
adrenaline, cortisol
glycemia
glycemia
response of lipolysis
lipogenesis
the body ketogenesis
proteosynthesis
proteolysis
from stores
source of
from food (glycogen)
glucose
gluconeogenesis
fate of glycolysis
glycolysis
glucose formation of stores
FASTING
WELL-FED STATE
STATE
source of
from food TAG from storage TAG
fatty acids
source of
from food TAG from storage TAG
fatty acids
proteosynthesis
fate of
oxidation gluconeogenesis
amino acids
lipogenesis
METABOLISM OF AMMONIA
•-SYNTHESIS
THE IMPORTANCE OF
OF NUCLEOTIDES ( NUCLEIC
GLUTAMINE
ACIDS) -
• DETOXIFICATION OF AMINO N (-NH 2
TRANSPORT)
• SYNTHESIS OF CITRULLINE (USED IN UREA
CYCLE):
EXAMPLES:
XENOBIOTICS INDUCTION OF CYT P450
HEME REPRESSION OF DELTA-
AMINOLEVULATE SYNTHASE
3. CHANGE OF ACTIVITY OF AN
EXISTING ENZYME
AVAILABILITY OF COENZYMES
CONSUMPTION OF PRODUCTS
PH CHANGES
• MODULATION OF ACTIVITY BY
MODULATORS (LIGANDS):
FEED BACK INHIBITION
PHOSPHORYLATION /
DEPHOSPHORYLATION
• DEPHOSPHORYLATION
PROTEIN PHOSPHATASE
INORGANIC PHOSPHATE IS THE PRODUCT!
Reversible covalent
modification:
A)
• phosphorylation by
a protein kinase
• dephosphorylation by
a protein phosphatase
B)
• phosphorylated enzyme
is either active or
inactive
(different enzymes are
influenced differently)
The figure is found at: http://stallion.abac.peachnet.edu/sm/kmccrae/BIOL2050/Ch113/JpegArt113/05jpeg/05_jpeg_HTML/index.htm
(December 2006)
MODULATORS OF ENZYME ACTIVITY
(ACTIVATORS, INHIBITORS)