Download Metabolism of Glucose C6H12O6+6O2 1 unit of Glucose 38 ATP

BIOCHEMISTRY – DR. WONG
2/19/2006 10:26:00 AM
Metabolism of Glucose C6H12O6+6O2
 1 unit of Glucose
 38 ATP
 need 6 unit of O2
 6 unit CO2
NAOH=3ATP
FADH2=2ATP
Net Chemical
1. Glycolysis
2. Intermediate
3. Kreb cycle
We have many tiny steps to extract the energy, otherwise the 38 ATP would
kill the cell.
Recap of Glycolysis (9 steps):
 Glucose –you bring the glucose to the mitochondria, you have to


provide ATP energy to the glucose to activate it (Glucose-6Phosphate. ‘6’ refers to the carbon atom). Phosphate is from ATP.
We have to modify the structure into Fructose-6-Phosphate.
Then into Fructose-1,6-diPhosphate
Why do we have to change the glucose into Fructose? We need the
second carbon to come off the ring to be available to react with the
phosphate. (check recording on this)
When they have enough energy, they split into two identical
molecules*.  into BPG Bisphosphoglycerate [DI for short, from DPG]
BPG is so important because it has a special function, it is the one that
gets the oxygen out of the hemoglobin.
o Temperature
o PH
o CO2 level
These all help BPG get O2 out of hemoglobin.
Note: *Should be 2 identical reactions.
*One 6C molecule turns into two 3C molecules. C6H12O6
o 3C molecule is small enough to pass through the outer
membrane of the mitochondria, that’s why it splits.
  Pyruvate (3C)
How much ATP can you extract from glycolysis only? 8 ATP
Body lost 1 ATP from first step.
Lost 1 more at the next step.
-ATP
-ATP
+ATP
+3ATP
+ATP
-2 ATP
x210 ATP
NET 8ATP
We always chose 8 ATP as the answer to how much APT is gained from
glycolysis.
Pyruvate (3C)
(Lack O2)
Anaerobic
NADH
Aerobic (O2)
2 x CO2
C02 out
Acetyl-CoA (2C) acetyl-coenzymeA
This acetyl-CoA goes into the Kreb’s Cycle (citric acid cycle)
This process enables the Glucose to pass through the inner membrane
of the mitochondria.
Matrix is called Matrix because it is very viscous/sticky. It’s filled with the
intermediate chemicals and enzymes.
At first two stages of the Kreb cycle, one CO2 is lost. It picks up 2C’s from
the acetyl-c.A  at 6C gives up one CO2 (and NADH) at 5C gives up CO2
(and NADH). It then gives up ATP, NADH, and FADH2.
We need to know that the Kreb cycle is continuous until the mitochondria
dies/stops. Also, the cycle will pick up 2 Carbon molecules from the acetylcoenzymeA.
 It gives up 2 carbon molecules each complete Kreb cycle.
 It gives up:
o 3NADH
9
1
2
12 ATP
o 1ATP
o 1FADH2
“12 ATP”
1 Glucose
2x Kreb Cycle
2x 12ATP/cycle
=2xATP
To better understand this, look at the link Dr. Wong sent out on the e-mail.
NOTES: Study where you see the Kreb cycle, the intermediate step. 2C can
pass through the membrane? Pyruvate is intermediate step? Inside, outside
of membrane?
How many CO2 comes out per cycle? 2
Glycolysis
Outer membrane
Pyruvate
Inner membrane
1C
2C
Pyruvate 3C  O2  Loss NADH (equivalent to ATP) Loss CO2 acetyl.cA
O2
No O2
38 ATP
“? ATP”
1 unit of Glucose in anaerobic pathway
Gly 8 ATP. Lost 6 ATP.
Body gains “2ATP”
From Pyruvate to Lactate (lose 3ATP).
Mental activity
O2/anaerobic
38
Blood supply provides more O2 to skeletal muscle,
giving more energy to you.
2ATP
Stop
So far, we’ve not seen oxygen really participate/get involved.
Now we will see it in the Electron Transport System (ETS): the job of
which is to convert e(-) acceptor into Energy
Lipid
Protein
Glucose
e(-) acceptors  ETS/Oxidative Phosphorylation
½ O2 (one O atom)
e(-)
O2 molecules
ETS is a chain reaction:
O2+
NADH, FADH2
H20
Every electron needs 1 oxygen atom.
The longer the distance the electron travels, the more energy that’s created.
e.g. ABCDE, etc, this is a chain reaction. The line above is a chain
reaction.
How many electrons are generated during the metabolism of glucose?
How many electron receptors are produced? 2. After the split they produce
one NADH.
x2=8
12 e(O2
Glycolysis
2 NADH
Intermediate
2 NADH
Kreb’s cycle
3 NADH
1 FADH2
4 e(-)acceptors
) acceptors  12 o-atoms  6
molecules
e(-)
NADHETS 
acetyl-c.A
Free NADH 
lactate
Note: Baroreceptors monitor how far the blood vessels are stretching.
If you eat more, you have to break down more O2 atom. Not stable (not
octet), it has to pick up e(-)/H+ from H2O to become stable. This leaves
more free radicals in the body and causes chaos in the body. Eating more
creates more free radicals.
BIOCHEMISTRY – DR. WONG
2/19/2006 10:26:00 AM
Nucleic Acids:


I. DNA – deoxyribonucleic acid
o Remove oxygen atom from ribose (a 5C sugar-carbohydrate)
II. RNA – ribonucleic acid
DNA
RNA
Double helix
3 different forms
One-form
MRNA (single strand)
tRNA – anti-codon
a.a.
tRNA ribosomal  ribosomes
Located inside the nucleus
Found anywhere inside the cell
DNA to RNA  transcription
NUCLEUS to RER  genetic materials
Structure of nucleic acid:
Polymer’s are combined monomers in a particular pattern
Polymer (many)
Monomer (single unit)
Protein
Amino acid
Carbohydrate: Starch (less soluble)
Glycogen (more soluble)
Glucose
Nucleic acid
Nucleotide – 3 chemicals
i) sugar - ribose (RNA) or
deoxyribose (DNA)
ii) phosphate – PO43iii) nitrogenous bases adenine A
 thymine T  replaced by Uracil U
 guanine G
 cytosine C
Double helix is governed by the Law of Complimentary Bases:
 If you have A on one side you must have T on the other side; etc.
Pairing is based on two considerations:
o Size of N-Bases
o Orientation – hydrogen bonding (intermolecular attraction
forces). No electron sharing; hence, not true bond.
A & G are Double Ring Structures (“Purines”) OO
T/U & C are Single Ring Structures (“pyridmidines”) O
Pairs occur between O (pyridmidines) and OO (purines)
BIOCHEMISTRY – DR. WONG
BIOCHEMISTRY – WONG
WEEK 9 – March 5th, 2006
Nucleic acid – Polymer
i) P
ii) Sugar
iii) N- bases
Repeating themselves in the same pattern
DNA – take out 1 O atom from the ribose.  Double helix  More room to
place the N-bases inside.
One would think that DNA is less stable than RNA, but DNA is actually more
stable.
Law of Complimentary Bases
Purines OO Pyrimidines O
Adenine
Thumine (Uracil)
Guanine
Cytosine
This maintains the width of the DNA double helix. If you have a single ring
on one side, there must be a double ring on the other side.
Hydrogen Bonding - Intermolecular attraction forces which are weaker
than ionic or covalent bond)
H-------N
H-------O
a-a-a-a-a-a-a-a-a-a-a-a-a
Hydrogen bonds between the alpha helix maintain strength of bond.
Consider the size of structure when evaluating the strength of hydrogen
bond. You aren’t responsible for this diagram, but in DNA this bond might
look like this:
N
C
C
N C
NH2
C
N
N C H
Adenine
Thymine
LIPIDS
I. Triglycerides (fat/oil)
1:3 ratio
Glycerol + Fatty Acids (Carboxylic acids + at least 12 carbon long)
C OH
C OH
C OH
O
HO-C-C-C-C-C-C-C-C-C-C-C-C
O
HO-C-C-C-C-C-C-C-C-C-C-C-C
O
HO-C-C-C-C-C-C-C-C-C-C-C-C
You don’t have to put all the hydrogen’s on the molecules any more.
However, put the bond marks on there.
Condensation bond
Glycolysis revisted:
1 glucose = “36 ATP”
NAOH=3ATP
FADH2=2ATP
O22ATP
Cristae is where the ETS is taking place. When Kreb cycle is
producing NAOH/FADH2 in the matrix and during glycolysis.
Glycolysis
Outer membrane
NADH
Pyruvate
NADH
Inner membrane
1C
2C
The longer the carbon chain you have, the more energy.
Fatty acid could have 12c, 14c, 16c, 18c, 20c, 22c, 24c…. etc.
even number.
Always an
II. Phospholipids - Major component of cell membrane
1glycerol:2fattyacid:1phosphate
 Glycerol: 2 F.A.
and one of the F.A. is replaced by Phosphate.
F.A. P PO43OH FA
OH FA
OH P
Amphipathic compound- partially in water, partially in non-water
molecule. Phospholipids are one of the few compounds that can do this.
This special criteria is necessary for forming a cell membrane like ours.
III. Wax - a long carbon chain. Alchohol + Fatty Acid (F.A.). Also form
condensation – esther bond (they have smell). Water insulation is property
of wax (for H20 insulation).
1:1 ratio
IV. Lipid Vitamins- not all vitamins are fat soluble. Some are water
soluble.
 H20 soluble:
o Bo C
Lipid soluble:
o A - Retinol (for vision); body converts carotene to retinol
because the body cannot eat Retinol directly (the liver breaks
it down and prevents its absorption).
o D - Calciferol
o E – Trocopherol (anti-oxidant; captures free radicals)
o K – this one has different forms. Sometimes it is given as an
injection – affects blood clots.
V. Steroids – OOOO four ring structure. 3 are hexagon, 1 is pentagon.
Don’t worry about learning how to draw this. This is a broad class;
including:
 cholestorol
 sex hormones
o estrogen
o testosterone
o androgen
aldostenone
BIOCHEMISTRY – Dr. Wong
3/12/06
Three components of Nucleic Acid:
 Phosphate
 Sugar
 Nitrogenous Base
Triglycerides (Fat/Oil):
 Glycerol + Fatty Acids (1:3)
(Glycerine)
Structural – manufactory of some other organic compound.
Gluconeogenesis…
Glycerol isn’t used for energy. The fatty acid IS used for energy.
H+ (water soluble). Acids are water soluble.
Carboxylic Acid is hydrophilic, atleast 12c or longer and of an even
number.
Name of Fatty Acid: 16:0 (The 16 means the number of C’s)(the 0
represents a saturated, single bond).
O
HO-C-C-C-C-C-C-C-C-C-C-C-C-C-C-C-C
1 2 3 4 5 6 7 8 9 (carbon molecules are numbered)
When labeled with Greek letters, it skips the fx grp.
Draw ALL the bonds
Draw: 18:1∆15
15th
(15)
The 1 refers to one double bond
-oxidation process
O
HO-C-C-C-C-C-C-C-C-C-C-C-C-C-C-C-C-C-C

Remove bonds from the bottom.
Don’t forget to put the functional group in here.
Put triple bonds on last carbon
If it is 18:3∆9,12,15, then the double bond is on the carbon’s between
9-10, 12-13, 15-16.
When there is more than one double bond, it is called Polyunsaturated
Fatty Acid (PUFA).
In order of Best to Worse FA:
 Unsaturated


Polyunsaturated (creates a lot of free radicals from the broken
double bonds)
Saturated
12:2∆7,10
Most Omega Fatty Acids are W3, W6, W9, W12, W15.
Metabolism of Triglycerides (Fatty Acids)
 I. -Oxidation (cutting process)
o Cutting occurs between  and  carbon. This is the oxidative

degradation of saturated fatty acids in which two-carbon units
are sequentially removed from the molecule with each turn of
the cycle.
II. Product acety-CoA 
This occurs within the Mitochondria.


I) 16c/2 – 1 = (7)x5 (1 NADH, 1 FADH2) = 35 ATP
II) 16/2 8 acety-CoA x 12 ATP = 96 ATP
I + II: 131 ATP – 2 ATP (two subtracted for the energy required to
push the fatty acid to the mitochondrial matrix) = 129.
Biochemistry
Lectures by Dr. Wong
3/19/06
Diabetes:
 Type I. Type II.
o Insulin causes the blood glucose level to go down.
 Brings glucose into the cells for metabolism
 Convert glucose (monosaccharide)  glycogen
(polysaccharide).
 Compare and contrast different kinds of sugars:
Starch
vs.
Glycogen
Straight Chain
Branched, globular




H2O insoluble
H2O soluble
Body can convert glycogen to glucose.
It can use:
 Glucagons
 Adrenaline/Epinephrine
B-cells in the Pancreas are responsible for producing
insulin.
A-cells in the Pancreas are responsible for producing
glucagons
Adrenal (medulla portion) glands are responsible for
producing epinephrine.
Potentiation and synergism mean the same thing:
 A-1
 B-1
 A+B2>more.
Drug-Drug interaction.
Liver Glycogen  Glucose
 Maintain blood sugar (glucose) level to provide enough glucose to
the brain.
Muscle Glycogen  Glucose
 Provide fuel to generate energy.
In exercise, first you burn off muscle glycogen, then liver glycogen, then
lipid. If you only exercise
In Diabetes, the cells cannot use glucose for energy. Only lipids. It depends
on lipids, but the the Fatty Acids produce much more acetyl-CoA that kreb
cycle cannot handle. This results in an accumulation of acetyl-CoA. The
body does NOT like this.
With too much acetyl-CoA, the body finds a way to get rid of it. It comes
out in the urine and in the breath. Every 2 acetyl-CoA combines together
forming a 4C molecule. This is called acetoacetic acid. There are two
functional groups in this: Ketone, Carboxylic Acid. The Ketone is liver toxic.
The Carboxylic acid is acidic. This can produce “acidosis”.
Down-regulation = glucose receptors turn inward and ignore insulin.
In the respiratory system, the acetoacetic acid is removed of O=C-O (CO2).
It results in propanone (acetone). This causes the loss of NADH
(“3ATP”)Acetone is the second component of the Ketone bodies. The ketone
is converted to alcohol by placing a Hydrogen next to it. With the addition of
another Hydrogen, it becomes octet. This is called -hydroxybutyric acid
(butanoic acid). Butyric and Butanoic is the same thing. It is called 
because it’s on the second carbon molecule. Clinical testing of urine (with
strip) measures the butanoic acid in the urine.
Ketone Bodies:
 Acetoacetic Acid (found in blood and urine)


Acetone (breath)
-hydroxybutyric acid (urine)
Neurotransmitter – GABA affects the CNS. It has an inhibitory effect on
CNS. For patients with convulsions. These convulsions could be caused by:
 Not produce enough GABA
 GABA receptors are/have been damaged
GABA stands for (gama)-amino-butyric-acid.
Acetyl choline is an excitatory neurotransmitter in the CNS. FYI.
TYPE I
TYPE II
Juvenile on-set
Adult on-set
IDDM – Insulin depedent diabetes
mellitus
NIDDM – Non-insulin dependant
diabetes mellitus
Insulin dependent
Insulin independent
Moderate genetic predisposition
Strong genetic predisposition
Prevalence 10-20%
>80%
Nutritional status undernourished
Obesity
Ketosis
Type I. Common
Type II. Rare
Oral hypoglycemic
Responsive
Unresponsive
Insulin level
Low (damaged on bcells)
Normal to high
(down regulation on
receptors)
BIOCHEMISTRY
Dr. Wong
3/26/06
Class of Chemicals:
Glycosaminoglycans (GAGs) – combination of protein and carbohydrate
together. Composed of:

Glucosamine

Glucouronic Acid – provide flexibility for the joints. Metabolism
occurs in the liver for detoxification (to make the chemical more
hydrophilic):
o Phase I – Oxidation; cytochrome P450
o Phase II – Conjugation (coupling); glucuronic acid
Phase II makes it hydrophilic. When drugs go through
phaze II metabolism, the drug is considered inactive.
Functions
o For body ground substance
 Connective tissues
 Cartilage


Ligament
Bone matrix
Examples made up of Glycosaminoglycans:
 Keratin (nails, cornea)
 Dermatan (skin; valves in circulatory system)
 Hyaluronic acid (shockabsorber)
 Heparin (anti-coagulating agent)
Metabolism of Protein (a.a)
 Peptide bond
 Protein to individual a.a.
Metabolism:
 I. Anabolism (build up)
 2. Abdomen (break downs)
-NH2
 NH3 + CO2 Urea (hydrophilic) in urine.
O
H2N – C –NH2
Urea + H2O