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Essential Biochemistry

The Basics...
1. Food and water is the basis of where we get energy from. Ö biochemistry is involved in
the chemical rxns that are required to be able to complete these processes.
2. How food turns into AT energy and water is important to !now. The food we eat must
first be converted to basic chemicals that the cell can use li!e sugars or carbohydrates
"accomplished by digestion#. These are bro!en down by en$ymes that split them into the
simplest form of sugar called glucose. %lucose then enters the cell by special molecules
in the membrane called glucose transporters "proteins#.
1. &ertain rxn steps are almost universal throughout body  'x. %lycolysis
2. (ther rxns are more confined to particular organs  'x. Thyroxine production
a. )hen a chemical rxn is organ*specific+ a lab test can detect the abnormal
production
b. 'x. , A-T . liver en$yme elevation can indicate presence of some !ind of liver
in/ury
0. AT "Adenosine Triphosphate# molecules 1 main energy source for biochemical rxns
a. 2t is used up quic!ly after being formed
b. Ö not a good form of storage
c. Better storage forms 1 %lycogen+ triglycerides
d. )hen necessary+ these storage molecules can be bro!en down and used to
regenerate AT or if not utili$ed it can be synthesi$ed into storage molecules
4. hosphorylation 1 transfer of a phosphate group. A3 4 → AT
a. hosphate groups contribute significant amounts of energy
b. 'x. ' is a very high energy molecule supplying a phosphate group in glycolysis
5. 6educing agents 1 supply H4 "electrons# in rnxs
a. 'x. 7A3H+ 7A3H+ FA3H2
b. 6elease energy "H4# upon reaction and become 7A3+ FA3
c. 7A3H is important and it differs from 7A3H cu$ it also gives off 4 H
8. (xidi$ing agents 1 receive H4 or electrons in rnxs
9. :ome chemical rxns transfer certain molecular groups in order for another rxn to
complete
a. 'x. %lucose ;"AT;A3#;%lucose*8* .transferring a H(:H(6<- group
=. 6ole of 'n$ymes. They do not supply additional energy or change the direction of a rxn.
2t merely speeds up a rxn that ordinarily ta!e a long time. 7ormally+ a substrate in a given
rxn requires a certain level of energy "a!a. energy of activation# for the rxn to ta!e place.
Therefore+ the rate of rxn is facilitated by en$ymes.
>. 'n$ymes facilitate brea!down and different en$ymes facilitate synthesis
a. 'x. %lycolysis. %lucose ;"%luco!inase# ;%lucose*8*
b. 'x. %luconeogenesis. %lucose*8*;"%luc*8*phosphatase# ;%lucose
10. Ö factors affecting rate of rxn are important to consider. 2ncreased Temperature
increases rate of rxn+ as molecules move faster+ thereby dispersing , concentration of
substrate and product of substrate are also important factors.
Glycolysis: Brea!down of glucose. 2 AT produced
(ccurs in cytoplasm
?. %lycogen stored in liver (6 active supply of glucose enters cell "that includes in 6B&@sA#
2. Brea! down via %lycolysis in the cytoplasm outside the mitochondria
0. 2f no (2 present. then only 2 AT is generatedBglucose molecule via anaerobic glycolysis
a. %lucose is bro!en down into pyruvate then converted to lactate "a!a. lactic acid#
b. However+ in muscles cells this leads to build up of lactic acid "a!a lactic acidosis#
c. 6emember. 6B&s have no mitochondria Ö this is normal AT generat@n
C. 2f (2 is present. 08 AT molecules generatedB? molecule of glucose bro!en down via
Dreb cycle and oxidative phosphorylation "'T&#
a. That is why mitochondria and oxygen are so important.
b. )e need to continue the brea!down process with the Drebs cycle inside the
mitochondria in order to get enough AT to run all the cell functions.
%lycogen -iver storage is used if no active supply avail.
E
%lucose*?*
E
%lucose*8*
F
%lucose 2f active supply avail. 'n$yme. %luco!inase "%D#
E
Fructose*8*
E
'n$yme. FD*?
Fructose*?+8*B
E
%lyceraldehyde*0*
E
E
hosphoenolpyruvate "'#
E
'n$yme. yruvate Dinase "D#
yruvate
;
-actate 2f no (2 presentG ex. Higorous exercise
E
if (2 present proceed to acetyl co*a in mitochond.
Acetyl &oA ?
st
step in progression to Dreb cycle stats with
0*& pyruvate  2*& "acetyl &oA#+ giving off &(2
Kreb Cycle & ETC
A!a. &itric Acid &ycleB(xidative hosphorylation. 08 AT produced
yruvate through to !reb cycle occurs in mitochondria
1. (xidation is stimulated by presence of A3 Ö in absence of A3+ oxidation slows+
providing a control mechanism with rate of oxidation matching need for AT Ö oxidation ,
when AT is low "and A3 high# and E when AT is high "and A3 low#
2. 'T&B(xidative phosphorylation restores 7A34
yruvate ; ? & is removed from 0*&
E
pyruvate therefore &(2 dispersed
Acetyl &oA
?# Acetyl &oA4(AA&itrate
(xaloacetate
I J
&itrate 'n$. &itrate synthas
, E
-eft side 'n$. Kalase
Kalate 2socitrate
, E
'n$. 2socitrate dehy.
Fumarate L*!etoglutarate -eft side 'n$. Fumarase
, E
'n$yme. L*!etoglu. 3ehydrogenase
:uccinate :uccinyl &oA -eft side 'n$. :uccinase

'n$. :uccinate thio!inase
%T %3 4 :ubstrate level phosphorylation
The whole idea behind respiration in the mitochondria is to use the Drebs cycle "a!a citric acid
cycle# to get as many electrons out of the food we eat as possible.
These electrons "in the form of H4 ions# are then used to drive pumps that produce AT. The
energy carried by AT is then used for all !inds of cellular functions li!e movement+ transport+
entry and exit of products+ division+ production of heme+ etc.
First+ pyruvate is required+ which is made by glycolysis from glucose. 7ext+ a carrier molecule is
required for the electrons.
There are two types. 7icotinamide Adenine 3inucleotide "7A34# and the other is called Flavin
Adenine 3inucleotide "FA34#. The third molecule+ of course+ is oxygen.
yruvate is a 0 carbon molecule. After it enters the mitochondria+ it is bro!en down to a 2 carbon
molecule. This releases carbon dioxide. The 2 carbon molecule is now called Acetyl &oA and it
enters the Dreb cycle by /oining to a C carbon molecule called oxaloacetate. (nce the two
molecules are /oined+ they ma!e a 8 carbon molecule called citric acid "2 carbons 4 C carbons 1
8 carbons#. That is where the &itric acid cycle got its name....from that first reaction that ma!es
citric acid. &itric acid is then bro!en down and modified in a stepwise fashion and+ as this
happens+ H4 ions and carbon molecules are released.
The carbon molecules are used to ma!e more &(2 and H4 ions are pic!ed up by 7A3 and
FA3. 'ventually+ the process produces the C carbon oxaloacetate again. The reason the
process is called a cycle+ is because it ends up always where it started....with oxaloacetate
available to combine with more acetyl coA.
OXIDATIVE PHOSPHORYLATION
6emember we said above. )hen you ta!e H4 ions "a!a electrons# away from a molecule+ you
oxidi$e that molecule. )hen you give H4 ions "a!a electrons# to a molecule+ you reduce that
molecule. )hen you give phosphate molecules to a molecule+ you phosphorylate that
molecule.
:o+ oxidative phosphorylation very simply means the process that couples the removal of H4
ions from one molecule and giving phosphate molecules to another molecule. :o how does
this apply to mitochondria nowM
As the Drebs cycle runs+ H4 ions "or electrons# are donated to the two carrier molecules in C of
the steps. They are pic!ed up by either 7A3 or FA3 and these carrier molecules become
7A3H and FA3H "because they now are carrying a hydrogen ion#.
These electrons are carried chemically to the electron transport chain found in the mitochondrial
cristae. The 7A3H and FA3H essentially serve as a ferry in the lateral plane of the membrane
diffusing from one complex to the next. At each site is a proton pump which transfers hydrogen
from one side of the membrane to the other. This creates a gradient across the inner
membrane with a higher concentration of H4 ions in the intercristae space "betBn inner 4 outer
membranes#.
There are individual complexes in the electron transport chain. The electrons are carried from
complex to complex by theseG they are !nown as  ubiquinone and cytochrome &.
The third pump in the series cataly$es the transfer of the H4 electrons to (2 to ma!e water.
This chemiosmotic pumping creates an electrochemical proton gradient across the membrane
which is used to drive the Nenergy producing machineN  AT synthase. This molecule is found
in small particles that pro/ect from the base of the cristae.
This process requires (2 which is why it is called Naerobic metabolismN. The AT synthase uses
the energy of the H4 ion gradient to form AT from A3 and hosphate. 2t also produces water
from the H4 and the (2. Thus+ each compartment in the mitochondrion is speciali$ed for one
phase of these rxn.
So, how is oxidation coupld to phospho!"lation#
6eview. 7A3 and FA3 remove the electrons that are donated during some of the steps of the
Dreb cycle. Then+ they carry the electrons to the electron transport pumps and donate them to
the pumps. :o+ 7A3 and FA3 are “oxidi$ed” bBc they lose the H4 ions to the pumps. The
pumps then transport the H4 ions to the space betBn the two membranes where they
accumulate in a high enough concentration to fuel the ATase pumps. )ith sufficient fuel+ they
“phosphorylate” the A3. That is how “oxidation” is coupled to “phosphorylation”.
The hydrogens that get pumped bac! into the matrix by the ATase pump then combine with
(2 to ma!e water "H2(#. And that is very important bBc+ without (2+ the H4 will accumulate and
the concentration gradient needed to run the ATase pumps will lac! and not allow the pumps
to wor!.
So, wh" do w nd $itochond!ia%
The whole idea behind this process is to get as much AT out of glucose "or other food
products# as possible. 2f we have no (2+ we get only 2 molecules of AT energy for each
glucose molecule "in anaerobic glycolysis#. However+ if we have oxygen+ then we get to run the
Dreb’s cycle to produce many more H4 ions that can run those AT pumps. From the Dreb’s
cycle we get 08 AT molecules out of one molecule of glucose converted to pyruvate "plus the 2
molecules we got out of glycolysis#. :o+ you can see how much more energy we can get out of
a molecule of glucose if our mitochondria are wor!ing and if we have oxygen.
? 2
0
C
5
Remember: 6B&@s do not have mitochondria therefore
are only capable of undergoing anaerobic glycosis. 'very
other cell in the body "muscle+ etc# have mitochondria
therefore are able to undergo aerobic glycolysis.
roblems occur when there isn@t enough (2 present to the
tissue cells  causing hypoxia  not allowing the tissue
to normally go thru glycolysis and !reb cycleA
Another process we need to !now is gluconeogenesis.
The reverse of glycolysis. forming glucose for storage
purposesA
Also. Heme productionO only possible via Dreb cycle as
production of :uccinyl &oA is the first step to production of
heme. Thin! about this  if no (2+ then no !reb cycle
then that means less production of heme that will mean
that there is decreased (2 being delivered to tissues
causing hypoxia and lead to necrosis of tissue cellsA That
means. B2% 6(B-'K if no (2AAAA
Gluconeogenesis
Formation of glucose "and subsequent glycogen#
(ccurs in cytoplasmG %lucose*8* thru to glycogen occurs in liver
%lycogen
,
'n$yme. %lycogen synthase
%lucose*?*
,
%lucose
,
'n$yme. %lucose phosphatase "%luco!inase "%D##
%lucose*8*
,
Fructose*8*
,
'n$yme. Fructose diphosphatase "Fru 2+8+B#
Fructose*?+8*B * activates FD*?
,
%lyceraldehyde*0*
,
,
hosphoenolpyruvate "'#
yruvate
6xn. yruvate  oxaloacetate  '
'n$yme. yruvate carboxylase
Acetyl &oA
P
(AA
• Process starts at Pyruvate coverting to PEP and up
• Opposite of glycolysis
Porphoryin: Heme Synthesis
?. orphobilinogen contains a single pyrrol ring
2. &overts to a quadruple*ringed porphyrinogen and prophyrin containing C pyrrhol rings
3. rotoporphyrin 4 iron "Fe24#  heme is produced+ with a central iron molecule "Fe24#
a. (ther molecules li!e Hitamin B?2 also get produced but with a central cobalt+
cytochromes+ catalase+ etc are formed as well
C. Hemoglobin"Hb# is formed by combination of heme 4 globin protein
5. Heme is a prosthetic group for a number of important molecules "Hb+ myoglobin+
cytochromes+ en$ymes such as catalase+ peroxidase "H2(2#+ etc#
8. Hemoglobin carries (2 in the blood "6B&#
a. Adult. Have C polypeptide chains. 2 alpha+ 2 beta  a!a HbA
b. Fetus. Have C polypeptide chains. 2 alpha+ 2 gamma  a!a HbF
9. Kyoglobin carries (2 in the muscles
=. (xidation of heme will lead to formation of bilirubin Q that will be discussed later