Download 24,7 Loctic Fermentotion

24.7 LacticFermentation 74,
of
AerobicCatabolism
from Complete
Table24.2ATPProduction
Molecule
OneGlucose
Pathway
Burning a mole of glucoseto
form CO2and H2Oproduces686
kcal of energy. Whenwe oxidize
a mole of glucose,the 38 mol of
AIP represents 277 kcal of stored
enelgy. Our bodies, then, are
about277kcal/686kcalx 100:
407oefficient.
glycolysis (4ATPgeneratedminus 2 invested)
citric acid cycle (2 acetyl groups of aceryl CoA
oxidized to carbon dioxide)
oxidative phosphorylation:
2NADH from glycolysis
2NADH from acetyl CoAformation
6NADH from the citric acid cycle
2FADH2from the citric acid cycle
AIPyield
2
2
6
6
1B
4
38
results.The data show that enough of the energyreleasedin the complete
oxidation of I molecule of glucoseis trapped by aerobic cells to generate
38 ATP molecules.
24,7 LocticFermentotion
AIM: To exploin why cells sometimesuse loctic fermentotionfor
energyProduction.
Focus
Aerobic cells switch to lactic or
alcoholic fermentation in the
absenceofoxygen.
So far our discussion of glucose metabolism has assumed that the cell
'vl/hatif it does not?
doing the metabolism has plenty of oxygen available.
We know that the mitochondria of aerobic cells need oxygen so that the
electron transport chain can operate.lVhen there is no oxygen available
to drain electrons from NADH and FADH2 in respiration, the electron
carriers of the electron transport chain become completely reduced.
More electrons cannot be passed down the chain, and oxidative phosphorylation stops. However, the levels of NADH and FADH2 in the mitochondrion increase as the citric acid cycle continues to operate. Soon,
not enough NAD* and FAD are regeneratedby respiration to sustain the
operation of the citric acid cycle, and the mitochondrial power plgnt
,/
shuts dor,rrn.
Now the only place that ATP is being produced is in the cytoplasm'
Here, two molecules of ATP are produced for every glucosemolecule converted to two molecules of pyruvate in glycolysis' Cytoplasmic NAD* is
also being reduced to NADH, and NAD* is needed for glycolysisto continue. (It is needed to changeglyceraldehyde3-phosphateto 1,3-bisphosphoglycerate.)If there were no way to regenerateNAD+, glycolysis too
would stop.With no energyproduction, the cell would die.
In such an emergency,the cells of many aerobic organismsregenerate
NAD* from the NADH formed in glycolysis by using the NADH to reduce
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CHAPTER
24 Carbohydrates
in LivingOrganisms
pyruvate to lactate.
o.o
o.o
\,/
l
,
CH.
\,/
C
-Z=\-+
NADH+ H'
H-C-OH
NAD.
Plruvate
I
CH,
Lactate
The reduction of pyruuate to lctctateis calledlactic fermentation. (For more
information, seeA closer Look Monitoring Heart Attackswith Serum LDH
Tests.)Lacticfermentation keepsglycolysisgoing.since aerobiccatabolism
produces 38 ArP moleculesfrom I molecule of glucoseand lactic fermentation produces only 2, the aerobic catabolismof glucoseis rg times more
efflcient than lactic fermentation. Nevertheless,considering the choices
between death and life at a lower level of AIP production, lactic fermentation is not a bad bargain for the cell.
'
Monitoring Heart Attacks
with SerumLDH Tests
Many clinical laboratorytestsin hospitalsmeasure
the amount of a criticalen4rmein the bloodstream.
One such enzlirne, lactate dehydrogenase(LDH), is
an important catalyst,promoting the reducfion of
p),r'uvateto lactatein your body.Consistingof four
polypeptide chains or tetramer subunits, LDH
exhibits multiple molecular forms called isozymes.
LDH is composedof two principal kinds of subunits, H and M, that differ slightty in their primary
strucl.ures.The five isoz).'rnesof LDH, H4, H3M.
HzMz, HM3, and Ma, are various combinations of
thesesubunits.Heart and liver LDH is rich in H
subunits;muscleLDH is rich in M subunits.
Becausedamaged tissuesoften releaseLDH
into the bloodstream, certain diseasescan be
detected by a clinical laboratory test that measures serum IDH levels. ln this procedure, a
patienl'sblood sample is analyzed,and the rate at
which the serum converts pyruvate to lactate is
obtained.This rate,in turn, determinesthe level of
LDH that may ind-icate a general abnormaliry.
Often it is useful to track the course of diseasein
specific tissues.A diagnosiscan be refined by
using another technique called electrophoresis
to
separatethe total LDH in a blood sampleinto its
variousisozymes(seefigure).Abnormal amounts
o
o
Direction of migration
ffiffi
€,# '@ffi
€
)
M4
HMs
HzMz
HsM
H4
Origin
Electrophoresisof serum LDH isozymesat pH 8.6: patte-rn4 belongsto a heartattackpatient;patternI is that
of a normalindividual.
Leakage
of cellcontentsof damagedheart musclein the heartattackpatienthassubstantiallyincreasedthe serumlevetof ihe Ho isozyme,
of a given isozyme can, in turn, narrow the search
for diseaseto specific organs or help monitor the
magnitude and courseof diseasein the body.
During a heart attack, for example, damaged
heart muscle releases LDH, mainly the H4
isoz],.rne.
Within 24 hours of the heart attack
episode, serum LDH reaches a peak; it then
returns to a normal level within 5 or 6 days. A
physicianoften can get a good idea ofthe extent of
a patient's heart damage by carefully monitoring
the amount of Hn isozl.rneover this pbriod of time.
24.8 OxygenDebt
745
The product of fermentation processesis not always lactate' Some
organisms-brewer's yeast is a particularly well-knor,rmexample-oxtdize
the pyruvate formed in glycolysisto acetaldehyde.
oo-
\,/
C
I
c:o
o\
-..---
rl
c
.1H
+co2
CH:
CHS
Pyruvate
Acetaldehyde
'
The reduction of acetaldehyderegeneratesNAD to keep glycolysisgoing.
The reduced product ofacetaldehyde reduction is ethanol.
H
o
\/
C
I
I
----Z---NADH+H
H-C-OH
NAD*
|
CH.
CHs
Acetaldehyde
Ethanol
The processby which glucoseis degradedto ethanol is called alcoholic fermentation.
24.5
EXERCISE
PRACTICE
Aerobic catabolism of glucose is much more efficient than fermentation.\.^/hat does this statement mean?
24.8 Oxygendebt
AIMS: Todescribethe conditionsthot could couseo stoteof
oxygendebt. To outline two possiblefates of loctote once
cellular respirotionis returned to normol.
Lactate is oxidized to carbon
dioxide or made into glucose.
Your respiratory system supplies the mitochondria of your body cells with
enough oxygen to operate their respiratory chains efficiently at normal levels of activity. If you undertake vigorous exercise,such as spdnting or longdistance running, your cells step up respiration to make AIP to megl/their
increased energy needs. You breathe more rapidly and more deeply, but
eventuallyyou may develop an oxygen debt-that is, not enough oxygenis
auailable for cellular respiration. At this point, your muscle cells begin to
use the much less efficient lactic fermentation route to make AIP
Lactate butldup
Lactate builds up as your cells regenerateNAD+ from NADH by lactic fermentation. If you have an oxygen debt and do not stop to rest, the lactic
acid concentration in your muscles continues to build. Lactic acid is toxic
to muscle cells in high concentrations and results in muscle cramps and
soreness.(Rememberhow you felt the day after a long-distance run oI
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24 Carbohydrates
CHAPTER
in LivingOrganisms
swim?)If you push on much further, you will soon collapse,becauselactic
fermentation cannot supply enough ArP to take care of your body's heavy
demands.
If you do stop to rest, you will pant as your respiratory system supplies
the oxygen necessaryto pay the oxygen debt. your cellular respiration is
soon restored to normal, but body cells must still deal with the lactate built
up during lactic fermentation.
Lactate
disposal
some of the lactate is oxidized babk to pyruvate by a reversal of the lactic
dehydrogenase-catalyzed reactions.
o.
o-
oo-
\,/
C
I
H-C-OH
I
CHu
\,/
C
NAD-
I
I
C:O
\
NADH + H
CH.
Lactate
Pyruvate
The NADH that is formed enters the respiratory chain, where AIp is produced by oxidative phosphorylation. The pyruvate is converted to acetyl
CoA,which enters the citric acid cycle.There the acetyl group of acetyl CoA
undergoes complete oxidation to carbon dioxide.
Some of the lactic acid formed in your muscles is not oxidized. It drains
from the muscle cells and enters the bloodstream, where it could give you a
severecase of acidosis.As we learned in Chapter 22, however,blood is
buffered. Your blood buffers, mainly the HCO3- /H2C03 system,will absorb
the extra protons added to your bloodstream by the lactic acid. And if need
be, your kidneys will generate new bicarbonate buffer ions that are lost as
carbon dioxide through breathing. Your kidneys also will expel excessprotons in your urine.
Gluconeogenesis
The lactic acid in your bloodstream is absorbed by your liver. Liver cells,but
not muscle cells, can convert lactate back to glucose in severalsteps.
\//
C
i
H-C-OH
oo\
,,,
C
I
I
2 H-C-OH
CH.
Severalsteps
-z---6ATP
6ADP
I
I
HO-C-H
H-C-OH
I
H-C-OH
I
cH2oH
Lactate
Glucose
24.8 OxygenDebt
Gluconeogenesis
gluco (Greek): sweet,glucose
neo (Greek): new
genesis(Greek); creation
747
The pathway by which lactate is conuerted to glucose is called gluconeogenesis. Gluconeogenesis,which is the synthesis of glucose from
startingmaterials that are not carbohydrates,is an exampleof an anabolic
(synthetic) pathway. Like most anabolic pathways, it requires the expenditure of ATP Six molecules of ATP are required to convert two molecules
of lactate to one molecule of glucose.However,only two molecules of ATP
were gained by converting one molecule of glucose to two molecules of
lactate in lactic fermentation. Your liver cells must pay for this deficit of
ATP They do so with the abundantATP produced in oxidative phosphorylation.
We will not be studying gluconeogenesisin detail. Nevertheless,the
first step of the pathway is partidularly interesting becauseit is also relevant to the citric acid cycle. It involves the chemical combination of
pyruvate and carbon dioxide, a carboxylation reaction, to give oxaloacetate.
corI
C:O
I
+
corI
CO:
ATP
\
ADP + P,
CH.
C:O
I
I
CH,
Cor$'ruvate
Carbon
dioxide
Oxaloacetate
The carboxylation of pyruvate is energetically unfavorable and
requires the expenditure of one of the sixAIP molecules invested in gluconeogenesis.Pyruvate carboxylase,the enzyme that catalyzes the reaction, requires the B-complex vitamin biotin as the coenzyrne.The biotin
servesas a carrier of carbon dioxide in this and other biological carboxylation reactions in the form of carboxybiotin. It is attached to the sidechain terminal amino group (not the alpha amino group) of a lysine
residue of the protein through an amide bond.
Carboxybiotin
The oxaloacetateproduced in the reaction meets one of two fates: It is
converted to glucosein the remainder of the reactions of gluconeogenesis, or alternatively, it may enter the citric acid cycle. Indeed, the carboxylation of pyruvate is the major source of oxaloacetatefor the citric acid
cycle.