Photosynthesis

1

• Photosynthesis
• Light reaction non cyclic pathway
• (Photosystem I and II)
• 2 H2O 2 NADP
• O2 2 NADPH 2 H

8 h?
2

• Photosynthesis
• Light reaction cyclic pathway (photosystem I)
  (photophosphorylation)
• ADP Pi ATP
• No H2O is consumed
• No NADPH or O2 is produced.
• Only ADP is phosphorylated.

Proton gradient
3

• Photosynthesis
• Dark reaction Calvin cycle
• 6 CO2 12 NADPH 12H 18 ATP 12 H2O
• C6H12O6 12 NADP 18 ADP 18 Pi

Rubisco and
Phtophorespiration RuBP O2 ? ? ? CO2
Rubisco
4
Metabolism of Lipids   I. Triacylglycerols   Tria
cylglycerol molecule from diet or fat cells can
be hydrolyzed by lipases to yield one glycerol
and three fatty acids.
Fatty acids can be oxidized to produce energy
glycerol can be converted to dihydroxyacetone to
enter the mainstream of carbohydrate
metabolism.
5
Lipolysis Fat (triglyceride)
glycerol fatty acids
(Lipase)
  Glycerol ? dihydroxyacetone phosphate ? G3P ?
? pyruvate ? TCA cycle Fatty acids ? ? oxydation
? (Acetyl-CoA)n ? TCA cycle.
6
Activation of fatty acids Before entering
?-oxidation pathway, fatty acids must be first
activated and labeled for degradation.
Fatty acids are activated by combining with CoA
and forming fatty acyl CoA (fatty acid CoA).
7

• Activation of fatty acids requires energy.

CoA-SH
O
O


R-CH2-CH2-C-S-CoA
R-CH2-CH2-C-OH
fatty acyl CoA
fatty acid
ATP
AMPPPi
The enzyme involved are acyl CoA synthase.
8
Activation of fatty acids is a two step
reaction Fatty acids Fatty acyl AMP
Fatty acyl CoA Pi AMP Fig. 18.4
ATP CoASH
(1) (2)
9
Fatty acids in muscle cells

• Fatty acids are delivered to muscle cells by
  blood stream.

• Upon entering the cell, fatty acids are
• immediately activated by linking to CoASH.
• Activation of fatty acids is coupled with their
  transport into mitochondria where the
  enzymes
• for fatty acid oxidation (?-oxidation) are
  located.

10
Transport of fatty acids across the inner
membrane of mitochondria is aided by the
molecule, carnitine. The long chain acyl group
is linked to carnitine. (carnitine
transferase). Acyl carnitine is transported
across the membrane by acyl carnitine
translocase. In the matrix, Acyl group is
cleaved from carnitine and recombined to
CoASH. Fig. 18.6
11
?-oxidation

• Fatty acids are recycled through the same five
  step cycles.
• Two carbons are removed in each cycle.
• The product, acetyl CoA then goes on to the
• citric acid cycle for energy production.

12
Why call it ? oxidation?
In this process, the ? carbon on the fatty acid
is oxidized.
O
? carbon
CoASH
C
C
C
C
CoA
C
C
C
C
S
O
C
C
C
C
C
CoA
O
C
C
C
C
C
S
C
CoA
C
S
? carbon
13
Four steps of ?-oxidation 1). Oxidation of C-C
to form CC double bond
2). Addition of H2O to form a -OH group on one of
the carbons 3). Oxidation of the -OH to
form a keto group 4). C-C bond cleavage,
releasing acetyl CoA, in the mean time another
CoA is added to the fatty acid chain resulting a
new fatty acyl CoA with two carbon shorter.
The new polymer is ready to enter another round
of ?-oxidation
14
?-Oxidation
acyl SCoA from activation step
FAD
acyl SCoA dehydrogenase
(1)
FADH2

(4)
H2O
(2)
CoA-SH
(3)
NADH H NAD
15
net reaction of ?-oxidation
O
CH3(CH2)16C-S-CoA 8 FAD
8 NAD 8 H2O 8 CoA-SH
O 9
CH3C-S-CoA 8 FADH2 8 NADH 8 H
Acetyl CoA is further oxidized by the citric acid
cycle. Energy from FADH2 and NADH is then
converted to ATP via the electron transport
chain and oxidative phosphorylation. Study Fig.
18.9 !
16
Significance of ?-oxidation Fatty acids are
degraded into many 2C units acetyl CoA that is
ready to enter TCA cycle.
Since the location of both ?-oxidation and TCA
cycle is in mitochondria, there is no need for
transport between different compartments of
cell.
17
?-oxidation of palmitate, a 16C FA can generate
8 acetyl CoA, 7 NADH , and 7 FADH2.  
Each A-CoA can generate 12 ATP through TCA cycle
and ETS. NADH and FADH2 can be oxidized through
ETS. After complete oxidation, a 16C palmic
acid can generate 129 ATP.
18
After complete oxidation, a 16C palmic acid can
generate 129 ATP.

• Step ATP/Unit Total ATP
• Activation step -2
• 7 acetyl CoA 12 96
• 7 FADH2 2
  14
• 7 (NADH H ) 3
  21
• Total ATP 129

19
  Direct comparison can be made between one 18C
FA and three 6C glucose. 18C FA ? 155 ATP 3
Glucose ? 114 ATP
20
Why lipid is not the first choice for cells to
get energy from? Fat molecule is a good
energy stock, but when the fat droplets are too
big, it is hard for the water- soluble enzymes to
work on them.
Also, the rate of ? oxidation is limited by the
O2 supply in mitochondria. As a result,
lipids cannot provide large amount of ATP in
short time.
21
Metabolism of ketone bodies Under normal
condition, carbohydrates is the major fuel
source, and produce gt 50 energy.
Under abnormal condition such as starvation or
uncontrolled diabetes, cells are unable to
obtain glucose, which makes fatty acids the major
energy source.
22
Problem some organs (brain cells) cannot use
fatty acids as energy source. When carbohydrate
is not available, glucose has to be synthesized
from oxaloacetate through gluconeogenesis.  
23

• First step in the citric acid cycle
• acetyl CoA oxaloacetate
  citrate
• (starvation)

gluconeogenesis
glucose
24
When there is lack of glucose supply a),
Excessive A-CoA are produced from excessive
?-oxidation b), Oxaloacetate level is
decreased, due to the synthesis of glucose
(to supply energy to brain).
The result is that acetyl CoA cannot be all
metabolized through TCA cycle due to the
deficiency of oxaloacetate. Excess A-CoA has
to enter anaerobic metabolism to produce ketone
bodies.
25
Ketogenesis

• Pathway for the production of ketone bodies.

O

2 CH3 -C S-CoA
acetyl CoA
O
O
CoA

CH3-C-CH2-C S-CoA
acetoacetyl CoA
26
O

(2C)
2 CH3 -C S-CoA
acetyl CoA
CoA
(6C)
?-hydroxy-?- methylglutaryl CoA
Acetoacetyl CoA
(4C)
(HMG CoA)
acetyl CoA CoA H2O
acetyl CoA
(4C)
acetoacetate
NADH H
H
NAD
(3C)
(4C)
?-hydroxybutyrate
acetone
CO2
27
(HMG CoA)
Acetone odor like rotten apple in breath
and urine
28
Ketosis (Ketoacidosis)

• Abnormally high concentration of ketone bodies in
  the blood from starvation, low carbohydrate
  diet, and diabetes mellitus ketoacidosis
• Two of the ketone bodies (acetoacetate and
• ? -hydroxybutyrate) are acidic which causes
  lowering of blood pH.

29
(No Transcript)
30
May 7, 2002
Triacylglyceral Glyceral ? dihydroxyacetone ?
G3-P Fatty acids Fatty acyl CoA -----
? ?-oxidation Lipolysis occurs in the cytoplasm,
where as ?-oxidation occurs in mitochondria.
31
Carnitine is being used in weight control
products to enhance utilization of fatty acids.
32
?-Oxidation
acyl SCoA from activation step
FAD
acyl SCoA dehydrogenase
(1)
FADH2

(4)
H2O
(2)
CoA-SH
(3)
NADH H NAD
33
After complete oxidation, a 16C palmic acid can
generate 129 ATP.

• Step ATP/Unit Total ATP
• Activation step -2
• 8 acetyl CoA 12 96
• 7 FADH2 2
  14
• 7 (NADH H ) 3
  21
• Total ATP 129
• Calculation of ATP yield through electron
  transport
• system is not consistent. Therefore, a 16C 129
  ATP
• or 106 ATP, 18C can be counted as 155 or 144 ATP)

34

• First step in the citric acid cycle
• acetyl CoA oxaloacetate
  citrate
• (starvation)

gluconeogenesis
glucose
35
O

Ketogenesis
(2C)
2 CH3 -C S-CoA
acetyl CoA
CoA
(6C)
?-hydroxy-?- methylglutaryl CoA
Acetoacetyl CoA
(4C)
(HMG CoA)
acetyl CoA CoA H2O
acetyl CoA
(4C)
acetoacetate
NADH H
H
NAD
(3C)
(4C)
?-hydroxybutyrate
acetone
CO2
36
Starvation andketone bodies
Blood Concentration (millimolar)
Weeks of Starvation
37
The brain
Glucose is primary energy source. Accounts for
about 60 of all glucose used by the body. If
glucose drops, it will use ketone bodies. Will
not use fatty acids They cant pass the
blood-brain barrier.
38
Biosynthesis of fatty acids

• Food is not our only source of fat.
• All organisms can synthesize fatty acids for long
  term energy storage and use in membrane
  structures.
• In humans, excess acetyl CoA is converted to
  fatty acids
• Occurs in cytoplasm, catalyzed by fatty acid
  synthase.
• A C3 precursor, malonyl CoA, is used to add
• carbon units to a growing chain.

39
The raw material for fatty acid synthesis is
acetyl CoA. All Acetyl CoA is synthesized
inside of the mitochondria, and has to be
transported to cytoplasm for the synthesis of
fatty acids.
40
Transcarboxylate translocase
41
Activation of acetyl CoA formation of malonyl
CoA CH3CSCoA CO2 ATP
CH2CSCoA ADP Pi O COO- . Acetyl
CoA and malonyl COA are then linked to acyl
carrier proteins (ACP) (a component of fatty acid
synthase).
O
CoA carboxylase
Acetyl CoA Malonyl CoA
42
Steps infatty acid synthesis
O
O


ACP CO2

H3C-C-S-ACP
-OOC-CH2-C-S-ACP
malonyl-ACP
acetyl-ACP
O
O


H3C-C-CH2-C-S-ACP
repeat
O
acetoacetyl-ACP

H3C-CH2-CH2-C-S-ACP
NADPH H
butyryl-ACP
NADP
H2O
H
O
NADP


O
H3C-C-CH2-C-S-ACP

NADPH H

H3C-CHCH-C-S-ACP
HO
?-hydroxybutyryl-ACP
crotonyl-ACP
43
Differences Between Fatty Acid Synthesis and
Degradation

• Synthesis of fatty acids occurs in cytoplasm
• degradation happens only in the mitochondria
• NADH and FADH2 are produced with degradation
  (oxidation)
• NADPH is used for synthesis (reduction).

44
Role of the liver in fat regulation

• The liver plays a major role in controlling fat
  usage and production.
• Regulates blood glucose levels by conversion to
  and from glycogen.
• Will make fatty acids if there is an excess of
  glucose and glycogen.

45
The liver
Glycogen Glucose-6-phosphate
Glucose
Used as fuel
Fatty acid synthesis
Glucose from blood
After a meal
VLDL sent to adipose tissue
46
The liver
Fatty acid used as a fuel
Glucose to blood
After fasting
Fatty acids sent from adipose tissue
47

• Adipose tissue is the major storage site for
  fatty acids.
• Fatty acids are transported from liver to adipose
  tissue as VLDL complexes.
• Fatty acids are then reconverted to
  triacylglycerols in the adipose cell for storage.

48
II. Cholesterol

• Cholesterol was first isolated from gall stones
  in 1784.
• This 27 carbon species is synthesized entirely
  from acetate (acetyl CoA).

49

• Cholesterol has bad reputation, but is also
  essential to all animal life

• Animal cell membranes structure.
• Precursor of steroid hormones, bile salts and
  vitamin D.  
• The key is to control cholesterol levels in
  normal
• range.
• Cholesterol can be from diet and can also be
• synthesized in the liver.

HO
50
Cholesterol biosynthesis a four stage process

• Stage 1 Synthesis of mevalonate
• Three acetyl CoA are condensed into the 6C
• mevalonate.
• One important intermediate in the first stage is
• HMG CoA (3-hydroxy-3-methylglutaryl CoA),
• which is then reduced to become mevalonate.
• The reactions occur in the cytoplasm of liver
• cells.

51
O
Fig. 18.20 on p508.

(2C)
2 CH3-C S-CoA
acetyl CoA
CoA
(6C)
3-hydroxy-3- methylglutaryl CoA
Acetoacetyl CoA
(4C)
(HMG CoA)
acetyl CoA CoA H2O
NADPH
First two steps are identical to reactions for
the production of ketone bodies.
NADP CoASH
L-Mevalonate (6C)
52
O

(2C)
2 CH3 -C S-CoA
acetyl CoA
CoA
(6C)
3-hydroxy- 3- methylglutaryl CoA
Acetoacetyl CoA
(4C)
(HMG CoA)
acetyl CoA CoA H2O
acetyl CoA
(4C)
acetoacetate
NADH H
H
NAD
(3C)
(4C)
?-hydroxybutyrate
acetone
CO2
53
O

2 CH3 -C S-CoA
acetyl CoA
CoA
Acetoacetyl CoA
HMG CoA
(4C)
acetyl CoA CoA H2O
HMG CoA reductase
NADPH
NADP CoASH
L-Mevalonate
54
HMG-CoA reductase catalyzes the convertion of HMG
CoA to mevalonate and is allosterically
regulated by diet cholesterol and other
cholesterol compounds.  
High diet cholesterol inhibits HMG-CoA
reductase, so that blood cholesterol level will
be balanced. Lipitor HMG-CoA reductase
inhibitor.
55

• Stage 2. C6 mevalonate converted to to C5
  intermediates.
• Mevalonate is phosphorylated and decarboxylated.
• The end products are two activated isoprenes,
• isopentenyl pyrophosphate and dimethylallyl
• pyrophosphate.

56
Dimethylallyl pyrophosphate.
57

• Stage 3. Synthesis of squalene.
• C30 hydrocarbon produced by successive
• condensations of isoprene units.
• isopentenyl pyrophosphate dimethylallyl
  pyrophosphate
• Geranyl pyrophosphate (10C)
• isopentenyl pyrophosphate
• PPi
• Farnesyl pyrophosphate (15C)
• Farnesyl pyrophosphate
• Squalene (30C)

(5C) (5C)
58
(No Transcript)
59
(No Transcript)
60
Stage 4 Cyclization of squalene and formation
of cholesterol. Squalene Squalene
2,3-epoxide Lanosterol Cholestrol
61
several steps
lanosterol
many reactions
cholesterol
squalene
62
Cholesterol is the precursor of other
steroids(Fig. 18.25)
Cholesterol
Bile salts
Vitamin D
Progesterone
Glucocorticoids
Androgens
Mineralocorticoids
Glycogen synthesis Na and water retention
Estrogens
63
(No Transcript)
64
Transport of cholesterol Cholesterol is a
water-insoluble molecule that is difficult to
dissolve and transport. Transport of lipids in
blood relies on lipoproteins - nonpolar lipids
are carried in the blood as lipoprotein
complex. Apolipoprotein lipids lipoprotein
65
Chylomicrons triacylglyceride cholesterol
proteins phospholipids Spherical
structure with proteins and polar lipids lined
outside and nonpolar lipids inside.
66
Structure of a chylomicron
apolipoprotein
triacylglycerol
cholesterol
phospholipid
67

• Four major classes of lipoproteins are used to
  transport lipids in the blood.
• Chylomicrons
• Very low-density lipoproteins (VLDL)
• Low-density lipoproteins (LDL)
• High-density lipoproteins (HDL)
• Each differs in types of apolipoprotein and the
  content of lipids.

68
Lipoproteins are classified according to their
density in centrifugation. The higher the
content of lipids the lower the density of the
complex.
69
Composition of complex lipoproteins
Chylomicron VLDL
triacylglycerol
phospholipid
cholesteryl ester
protein
cholesterol
other materials
LDL HDL
70
Function of lipoproteins

• Chylomicrons
• Transport triacylglycerols from intestines to
  other tissues. Account for most lipids in blood.

• VLDL
• Bind triacylglycerols in liver and carry them
• to fat tissue.
• LDL
• Carry cholesterol to peripheral tissues
• HDL (55 protein)
• Bound to plasma cholesterol. Transport
• cholesterol to liver (reverse transport).

71
Transport of lipoproteins
LDL transfers cholesterol to tissues from liver.
VLDL moves triacylglycerols from liver to tissues.
HDL carry cholesterol from tissues to liver.
Dietary fat
72
  LDL synthesized in liver, move cholesterol
from liver to peripheral tissues.
In tissues, LDL binds to LDL receptor and is
uptaken by the cells through endocytosis.
Inside the cells cholesterol is stripped from
LDL, and is used for membrane construction.
  Some times LDL may attach to vessel wall to
form cholesterol plaques.
73
Regulation of LDL

• Large number of receptors in liver allows rapid
  removal of LDL
• Genetic defect in LDL receptors
• Allows cholesterol to accumulate in the plasma -
  hypercholesterolemia.
• Excess cholesterol is then deposited in artery
  walls - atherosclerosis.
• Treatment in trial gene therapy

74
HDL (good cholesterol) Synthesized in the
liver, move in blood stream to peripheral tissue,
bind with cholesterol and bring it back to the
liver. Once inside liver cells, cholesterol is
used to produce bile salt or simply be excreted
in bile juice to the intestines.
 
75
The health problems related with cholesterol is
probably more due to the abnormality in
cholesterol transport.