continuation of bioenernetics

1. CHE 214: Biochemistry
Lecture Three
•BIOENERGETICS
Lecturer: Dr. G. Kattam Maiyoh
GKM/CHE 214/LEC 04/SEM 02/2013

2. The Brain Will Make Ketone Bodies If It’s Starving For
Glucose
Acetyl-CoA
Acetoacetyl CoA synthase
HMG CoA synthase
HMG CoAlyase
GKM/MLS2119/LEC 05/SEM 02/2013

3. Ketosis
• Blood ketone levels are usually very low
– many tissues use ketone bodies for ATP production
• Fasting, starving or high fat meal with few
carbohydrates results in excessive beta oxidation
& ketone production
– acidosis (ketoacidosis) is abnormally low blood pH
– sweet smell of ketone body acetone on breath
– occurs in diabetic since triglycerides are used for ATP
production instead of glucose & insulin inhibits
lipolysis
GKM/CHE 214/LEC 04/SEM 02/2013
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4. The Brain Will
Use Amino
Acids
To Make
Glucose If It
Has To
GKM/MLS2119/LEC 05/SEM 02/2013

5. Gluconeogenesis:
Synthesis
Of Glucose From
Pyruvate
Gluconeogenesis is not just
glycolysis in reverse--the
enzymes in green print
catalyze irreversible reactions
It requires cleavage of 6
phosphoanhydride bonds to
synthesize one molecule of
glucose from pyruvate--
4 from ATP and 2 from GTP
GKM/MLS2119/LEC 05/SEM 02/2013

6. Your Body has Several Sources of Pyruvate
Lactate from anaerobic respiration (ex. red blood cells,
working skeletal
muscle)
Amino acid breakdown
Glycerol from triglyceride breakdown
GKM/MLS2119/LEC 05/SEM 02/2013

7. Phosphofructokinase
and Fructose-1,6-
Bisphosphate are Glucose -6- phosphatase
Reciprocally Controlled
This is the primary means by
which the balance between
glycolysis and gluconeogenesis
is maintained
PFK is stimulated and F-1,6-B
is inhibited by
NAD+, ADP, and AMP
NADH and ATP have the
opposite effects
GKM/MLS2119/LEC 05/SEM 02/2013

8. Glucose-6-Phosphatase
Takes the Phosphate
Group off Glucose-6- Glucose -6- phosphatase
Phosphate to Make
Glucose
GKM/MLS2119/LEC 05/SEM 02/2013

9. Glycogenesis—Storing
The Energy for Later
Monosaccharides are activated by
linking them to
diphosphonucleotides
Ex. Glucose  glucose-6-P
glucose-6-p  glucose-1-p
Glucose-1-phosphate + UTP 
UDP-glucose + PPi
UTP is uracil triphosphate—another
phosphorylated nucleotide like ATP
GKM/MLS2119/LEC 05/SEM 02/2013

10. Glycogenesis—Storing the Energy for Later
The activated glucoses are chained together
to make the backbone of
glycogen by glycogen synthase—it makes
alpha-1,4 O-glycosidic bonds
The glycogen branching enzyme makes the
alpha-1,6 linkages that allow branches to
develop, making glycogen highly branched
GKM/MLS2119/LEC 05/SEM 02/2013

11. Glycogenesis & Glycogenolysis
• Glycogenesis
– glucose storage as glycogen
– 4 steps to glycogen
formation in liver or
skeletal muscle
– stimulated by insulin
• Glycogenolysis
– glucose release is not a simple
reversal of steps
– enzyme phosphorylase splits off a glucose molecule by
phosphorylation to form glucose 1-phosphate
– The enzyme is only in hepatocytes so muscle can’t release
glucose
– It is activated by glucagon 214/LEC 04/SEM 02/2013 epinephrine (adrenal)
GKM/CHE
(pancreas) &
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12. Gluconeogenesis
• Liver glycogen runs low if fasting, starving or not eating carbohydrates forcing
formation from other substances
– lactic acid, glycerol & certain amino
• Stimulated by cortisol (adrenal) & glucagon (pancreas)
– cortisol stimulates breakdown of proteins freeing amino acids
– thyroid mobilizes triglycerides from adipose tissue
GKM/CHE 214/LEC 03/SEM 02/2011
04/SEM 02/2013
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13. Transport of Lipids by Lipoproteins
• Most lipids are nonpolar and must be combined with
protein to be tranported in blood
• Lipoproteins are spheres containing hundreds of
molecules
– outer shell polar proteins
(apoproteins) & phospholipids
– inner core of triglyceride &
cholesterol esters
• Lipoprotein are categorized by
function & density
• 4 major classes of lipoproteins
– chylomicrons, very low-density, low-density & high-density
lipoproteins
GKM/CHE 214/LEC 03/SEM
GKM/CHE 214/LEC 04/SEM 02/2013
02/2011 25-13

14. Classes of Lipoproteins
• Chylomicrons (2 % protein)
– form in intestinal epithelial cells to transport dietary fat
• apo C-2 activates enzyme that releases the fatty acids from the
chylomicron for absorption by adipose & muscle cells
• liver processes what is left
• VLDLs (10% protein)
– transport triglycerides formed in liver to fat cells
• LDLs (25% protein) --- “bad cholesterol”
– carry 75% of blood cholesterol to body cells
– apo B100 is docking protein for receptor-mediated endocytosis
of the LDL into a body cell
• if cells have insufficient receptors, remains in blood and more likely to
deposit cholesterol in artery walls (plaque)
• HDLs (40% protein) --- “good cholesterol”
– carry cholesterol from cells to liver for elimination
GKM/CHE 214/LEC 03/SEM
GKM/CHE 214/LEC 04/SEM 02/2013
02/2011 25-14

15. Blood Cholesterol
• Sources of cholesterol in the body
– food (eggs, dairy, organ meats, meat)
– synthesized by the liver
• All fatty foods still raise blood cholesterol
– liver uses them to create cholesterol
– stimulate reuptake of cholesterol containing bile normally lost
in the feces
• Desirable readings for adults
– total cholesterol under 200 mg/dL; triglycerides 10-190 mg/dL
– LDL under 130 mg/dL; HDL over 40 mg/dL
– cholesterol/HDL ratio above 4 is undesirable risk
• Raising HDL & lowering cholesterol can be accomplished
by exercise, diet & drugs
GKM/CHE 214/LEC 03/SEM
GKM/CHE 214/LEC 04/SEM 02/2013
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16. Fate of Lipids
• Oxidized to produce ATP
• Excess stored in adipose tissue or liver
• Synthesize structural or other important
molecules e.g.
– phospholipids of plasma membranes
– lipoproteins that transport cholesterol
– thromboplastin for blood clotting
– myelin sheaths to speed up nerve conduction
– cholesterol used to synthesize bile salts and
steroid hormones.
GKM/CHE 214/LEC 03/SEM
GKM/CHE 214/LEC 04/SEM 02/2013
02/2011 25-16

17. Triglyceride Storage
• Adipose tissue removes triglycerides from
chylomicrons and VLDL and stores it.
– 50% subcutaneous, 12% near kidneys, 15% in omenta,
15% in genital area, 8% between muscles
• Fats in adipose tissue are ever-changing
– released, transported & deposited in other adipose
• Triglycerides store more easily than glycogen
– do not exert osmotic pressure on cell membranes
– are hydrophobic
GKM/CHE 214/LEC 03/SEM
GKM/CHE 214/LEC 04/SEM 02/2013
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18. Lipid Catabolism: Lipolysis
• Triglycerides are split into fatty acids & glycerol by lipase
– glycerol
• if cell ATP levels are high, converted into glucose
• if cell ATP levels are low, converted into pyruvic acid which enters
aerobic pathway to ATP production
GKM/CHE 214/LEC 03/SEM 02/2011
04/SEM 02/2013
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19. Lipolysis & Fatty acids
Liver cells
• Beta oxidation in mitochondria removes 2 carbon units from fatty
acid & forms acetyl coenzyme A
• Liver cells form acetoacetic acid from 2 carbon units & ketone
bodies from acetoacetic acid (ketogenesis)
– heart muscle & kidney cortex prefer to use acetoacetic acid for ATP
production
GKM/CHE 214/LEC 03/SEM 02/2011
04/SEM 02/2013
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20. Lipid Anabolism: Lipogenesis
• Synthesis of lipids by liver cells = lipogenesis
– from amino acids
• converted to acetyl CoA & then to triglycerides
– from glucose
• from glyceraldehyde 3-phosphate to triglycerides
• Stimulated by insulin when we eat excess calories
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