METABOLISM

Edited by Liniyanti D.Oswari,MD.MSc.

Metabolism = all chemical reactions
in the body

Two Basic Types of Reactions
Anabolic = build large molecules from small unit
molecules
Require energy

Catabolic = breakdown large molecules into
small unit molecules
Release energy
Oxidation Reaction = remove electrons and/or
H
+
from a molecule

Electron plus H
+
= ??

Anabolic or Catabolic ??

Requires Energy or Releases Energy ??
Reduction Reaction = add electrons and/or H
+

to a molecule

Electron plus H
+
= ??

Anabolic or Catabolic ??

Requires Energy or Releases Energy ??
Phosphorylation Reaction =
add phosphate (PO
4
-3
) to a molecule
Anabolic or Catabolic ??
Requires Energy or Releases Energy ??
Dephosphorylation =
Removing a Phosphate (PO
4
-3
)
Anabolic or Catabolic ??
Requires Energy or Releases Energy ??
The ATP Cycle
In cells when a Hydrogen (H) or an electron is
removed (oxidation) it goes immediately to
another molecule (reduction)

When energy is released (oxidation) it goes to
another molecule (reduction)

Combination = oxidation-reduction reaction
or Redox reaction

Cells keep some molecules around just to accept
H, electrons & energy from oxidation reaction
(to be reduced)

Adding H, electrons & energy to these
molecules would be a reduction reaction

One common group of these molecules are the
coenzymes
Two examples are NAD
+
and

FAD

Coenzymes
NAD
+
+ H
+
+ 2 electrons + Energy NADH

Identify the reduced coenzyme?
Identify the oxidized coenzyme?
Which form of coenzyme has more energy?

FAD + 2H
+
+ 2 electrons + Energy FADH
2

Identify the reduced coenzyme?
Identify the oxidized coenzyme?
Which form of coenzyme has more energy?
ENERGY FLOW

Glucose Coenzyme ATP
Oxidation Reduction Oxidation Phosphorylation
ENERGY ENERGY


ALL Reactions are controlled by ENZYMES
Gut-Brain Peptides
(only a few out of many)
Chemical signals from the G.I. Tract to the Brain

Short-term Regulators
Last for minutes to hours
Make us want to start eating and stop eating

Long-term Regulators
Work over periods of weeks to years
Regulate our caloric intake & energy spent and
amount of adipose tissue
Short-Term Regulators
Ghrelin
Secreted from parietal cells when stomach empty
& stops within an hour of eating
Produces sensation of hunger & starts up eating
Causes hypothalamus to release GHRH ( hGH)

Peptide YY
Secreted by ileum & colon in response to food in
the stomach, in proportion to calories consumed
Signals satiety & stops eating

Cholecystokinin
Secreted by duodenum & jejunum
Produces appetite-suppressing effect via Vagus N.
Long-Term Regulators

Leptin
Secreted by adipocytes in proportion to amount of
stored fat
Primary way brain knows how much body fat is
stored
Obesity is related to receptor unresponsiveness

Insulin
Secreted by beta cells in pancreas
Stimulates glucose & amino acid uptake
Promotes glycogen & fat synthesis
Additional way brain knows how much body fat is
stored (effect weaker than leptin)
The Arcuate Nucleus of the Hypothalamus is the
primary appetite regulation center in the brain
Secretes Neuropeptide Y = Appetite Stimulant
Ghrelin stimulates secretion
Peptide YY, leptin & insulin inhibit secretion

Secretes Melanocortin = Appetite Suppressant
Leptin stimulates secretion

Carbohydrate Metabolism
Monosaccharides absorbed;
Glucose
Fructose
Galactose
Fructose & Galactose are converted to glucose
in the liver
Carbohydrate metabolism =
Glucose metabolism
1) Glucose enters cells & is oxidized for energy
= Cellular Respiration
Aerobic or Anaerobic

Aerobic Cellular Respiration
C
6
H
12
O
6
+ 6O
2
6CO
2
+ 6H
2
O
Glycolysis

Net Production of Energy
Molecules

Per Glucose;
2 ATP
2 NADH

p 1014
Transition Reaction
Per Glucose;
2 NADH

Krebs (Citric Aid) Cycle
Per Glucose;
2 ATP
6 NADH
2 FADH
2

Per Acetyl CoA ??
p 1016
ENERGY FLOW

Glucose Coenzyme ATP
Oxidation Reduction Oxidation Phosphorylation
ENERGY ENERGY


ALL Reactions are controlled by ENZYMES
Electron Transport System
p 1018
p 1017
Oxidize NADH = 3 ATP
Oxidize FADH2 = 2 ATP
Electron Transport System
Oxidize NADH = 3 ATP
Oxidize FADH
2
= 2 ATP

Glycolysis 2 NADH X 3 = 6 ATP
Trans Rx 2 NADH X 3 = 6 ATP
Krebs 6 NADH X 3 = 18 ATP
2 FADH
2
X 2 = 4 ATP

TOTAL 34 ATP
p 1019
Only 2 ATP per Glucose

What happened to
2 NADH ?
p 1014
Anaerobic Cellular Respiration
= Glycolysis only
2) Excess glucose is stored as glycogen
Most (~80%) in skeletal muscle
Remainder in liver
Anabolic Rx: glucose glycogen = glycogenesis
Catabolic Rx: glycogen glucose = glycogenolysis
p 1020
3) If glycogen storage is full, glucose stored
as lipids (triglycerides) in adipose tissue
Triglyceride
Triglyceride
Glucose transformed into Triglyceride

Glucose PGAL Glycerol

Acetyl CoA Fatty Acids (beta reduction Rx)


Glycerol + 3 Fatty Acids Triglyceride
p 1022
4) Excess glucose may be excreted in urine

Glucose is considered an abnormal component of
urine, but with very high concentrations in blood
the kidneys cannot keep some glucose from
leaving the body

Sodium-glucose transport proteins get overwhelmed

Diabetes Mellitus = cells cant uptake glucose, so
concentrations remain very high in blood, causing
glucose to end up in the urine
Lipid Metabolism
p 1009
CHYLOMICRON PATHWAY: Chylomicrons absorbed from intestines
into lymphatic system & ultimately the bloodstream. Endothelial cell
surface enzyme, lipoprotein lipase, hydrolyzes triglycerides into
monoglycerides & free fatty acids.
p 1009
VLDL/LDL PATHWAY: Very low-density lipoproteins
(VLDL) transport lipids from liver to adipose for storage.
Triglycerides are stored in adipose, leaving low-density
lipoproteins (LDL) that contain mostly cholesterol.
LDLs enter cells that need cholesterol.
p 1009
HDL PATHWAY: High-density lipoproteins (HDL) leave
liver as empty protein shells that pick up cholesterol &
phospholipids. As HDLs pass through liver, cholesterol is
removed & liver removes as cholesterol and bile acids.
Chylomicron Pathway =
triglycerides from intestine to body cells


VLDL / LDL Pathway =
1st STOP: triglycerides from liver to adipose
2nd STOP: cholesterol from liver to body cells


HDL Pathway =
cholesterol from blood to liver
1) Lipids are taken up by the body cells for non-energy
uses
Cell membrane phospholipids, steroid hormones, etc.
Delivered by chylomicrons & VLDL/LDLs from liver

2) Much of the lipids are stored as triglycerides in
adipose tissue & the liver.
Delivered by chylomicrons & VLDL/LDLs from liver
p 1022
3) If blood glucose is low, triglycerides can be released
from the adipose to be oxidized for energy.

Beta-oxidation
of fatty acids
p 1022
Each beta oxidation reaction
releases enough free energy
to produce
5 ATPs

An 18-carbon fatty acid can
produce nine
2-carbon Acetyl CoA

How many beta oxidations
does it take ?
A beta oxidation reaction removes one acetyl group
(-COCH
3
) from a fatty acid to make one Acetyl CoA
p 1022
Each Acetyl CoA can
then enter into the
Citric Acid Cycle


How many energy
molecules will be
produced for each
Acetyl CoA?
p 1022
The liver can combine two
acetyl groups into one of
three compounds called
ketone bodies, which are
released into the blood.

Cells in heart and brain use
ketone bodies
to make Acetyl CoA which
then enter the
Citric Acid Cycle.
Protein Metabolism
Amino acids are absorbed
from the small intestine

About 50% from diet
About 25% from dead epithelial cells
About 25% from digested enzymes
1) Amino acids used for protein synthesis

Amino acids can be actively transported
into body cells & used to build proteins
What are some
examples of proteins?
20 different amino acids are used to synthesize
proteins

About half are called essential amino acids
because they must come from the diet

Foods that contain all the essential amino acids
are called complete proteins, for example;
eggs, milk, meat.

The nonessential amino acids can be produced by
the body through a process called
transamination

Transamination = transfer of an amino group (NH
2
)
from an abundant amino acid to a keto acid to
make a new amino acid

Keto acid + amino group (NH
2
) amino acid
2) Amino acids can be used as fuel, or a source of
energy

First step is deamination, which is removal of an
amino group (NH
2
) from an amino acid creating a
keto acid

Amino acid Keto acid + amino group (NH
2
)

Depending on which amino
acid is deaminated,

the keto acid may be
converted to;
Pyruvic acid
Acetyl CoA
One of the acids of citric
acid cycle

p 1023
Pyruvic acid could be
converted back into glucose
by cells in the kidney or liver

This is an example of
gluconeogenesis, which is
making glucose from a non-
carbohydrate source
p 1023
The amino group is transferred to
ketoglutaric acid, making
glutamic acid, that travels to the
liver & is converted back to
ketoglutaric acid


Left over ammonia (NH
3
) is
converted to urea
p 1023
p 1025
Absorptive State = 4 hours during & after a meal
Nutrients are being absorbed & then immediately used
or stored

Postabsorptive State = stomach & intestine are empty
Stored fuel molecules are used for energy