Lecture 17: Energy Balance and Metabolism I Flashcards
Define free energy and relate to exergonic and endergonic reactions.
> deltaG = standard free energy difference.
= difference in free energy when 1 mole of each reactant is converted to 1 mole of each product at 1 atm pressure at 25 C.
> negative deltaG = exergonic reaction
positive delta G = endergonic reaction
> ATP -> ADP + Pi delta G = -7300 cal/mole (at 25 C)
ATP -> ADP + Pi delta G = -12,000 cal/mole (at 37 C)
What does galactose, glucose, and fructose get converted to to enter the glycolytic pathway?
Fructose-6-Phosphate
List the multiple transport of glucose into tissue cells.
> Active sodium-glucose co-transport (active transport of sodium provides energy for absorbing glucose against a concentration gradient)
> Facilitated Transport (higher to lower concentration)
In the uptake of glucose, what does the presence of insulin do?
increases glucose transport x10
In the uptake of glucose, what does the phosphorylation of glucose do?
prevents diffusion out of cell
phosphorylation can be reversed in liver, renal, and intestinal cells
What factors can activate phosphorylase?
> epinephrine (from adrenal gland)
> glucagon (from alpha cells of pancreas)
In glycogenesis and glycogenolysis, what are the effects of phosphorylase?
> promotes conversion of glycogen to glucose
> glucose can then be released into blood
What enzyme does glycogen -> glucose-1-phosphate?
phosphorylase
What enzyme does glucose-6-phosphate -> blood glucose?
phosphatase
What enzyme does blood glucose -> glucose-6-phosphate?
glucokinase
What are the end products of glycolysis?
> Pyruvic acid (2 molecules)
Hydrogens (4)
ATP (2 molecules)
In the end of glycolysis, what enzyme catalyses the release of the 4 hydrogens produced?
dehydrogenase
Which steps in glycolysis is ATP used?
> glucose -> glucose-6-phosphate
> fructose-6-phosphate -> fructose-1,6-diphosphate
Which steps in glycolysis produces ATP?
1,3-diphosphoglyceric acid -> 3-phosphoglyceric acid
phosphoenolpyruvic acid -> pyruvic acid
What are the end products of pyruvic acid -> acetyl-CoA?
> acetyl-coa (2 molecules)
hydrogens (4)
carbon dioxide (2 molecules)
What enzyme catalyzes lactic acid formation from pyruvic acid?
lactic dehydrogenase
pyruvic acid + NADH + H -> lactic acid + NAD
fate of pyruvic acid when oxygen is not present
Where does the citric acid cycle occur?
mitochondrial matrix
What are the end products of the citric acid cycle?
> hydrogens (16)
ATP (2 molecules)
carbon dioxide (4 molecules)
What is the net reaction of the citric acid cycle?
2 acetyl-coa + 6 H20 + 2 ADP —>
4 CO2 + 16 H + 2 CoA + 2 ATP
Where does oxidative phosphorylation occur?
on mitrochondrial cristae
What is the fate of hydrogen atoms from glycolysis and citric acid cycle?
> Note that hydrogens are removed in pairs.
One member of each pair becomes a hydrogen ion.
The other member of a pair combines with NAD -> NADH
What is the fate of electrons removed from hydrogen ions?
enter electron transport chain
What are the major components of the electron transport chain?
> flavoprotein
> several iron sulfide proteins
> ubiquinone (Q)
> cytochrome A3 (cytochrome oxidase)
- located on inner membrane
- can give up electrons to oxygenList the steps of the chemiosmotic mechanism.
> electrons pass through chain, releasing large amounts of energy
> energy is used to pump hydrogen ions from inner matrix into outer chamber between inner and outer membranes
> high concentration of hydrogen ions created in chamber
> strong negative potential created in inner matrix
> hydrogen ions flow from high to low concentration through ATP synthetase
> energy derived from hydrogen ion flow is used by ATPase to convert ADP to ATP
> fore each 2 electrons that pass through electron transport chain, up to 3 ATP molecules are synthesized
> note that the 2 pairs of hydrogens derived from the citric acid cycle enter the electron transport chain at a later point and provide energy for 2 ATP molecules per pair
After oxidative phosphorylation, what is the number of ATPs formed per glucose molecule in each pathway?
Glycolysis - 2 ATPs
CAC - 2 ATPs
Oxidative Phosphorylation - 34 ATPs
What is the maximum number of ATPs that can be produced per glucose molecule?
38
How many calories are produced from 38 ATP molecules?
38 x 12,000 cal/mole = 456,000 calories/mole glucose
456,000/686,000 = 66% efficiency
What is the pentose phosphate pathway?
> The PPP is a cyclical pathway in which one molecule of glucose is metabolized for each revolution of the cycle.
-for every 6 glucose that enter pathway, 5 glucose are resynthesized.
> This pathway is mostly used for the synthesis of fats and other substances.
> Hydrogens generated from this pathway are bound to NADP instead of NAD.
What molecule from the PPP can be used in the synthesis of fats from carbohydrates?
NADP+ (as NADPH)
NOT NAD+ can be used in the synthesis of fats from carbohydrates
Where is excess glucose broken down by PPP?
liver
producing excess NADPH
What conversion does NADPH participate in?
Conversion of actyl-coa into fatty acid chains.
- glucose is preferentially stored as glycogen until the storage cells (liver and muscle) are saturated*
- excess glucose is then converted into fat (liver and fat cells) and stored in fat cells*
What is the net reaction of PPP?
glucose + 12 NADP + 6 H20 –> 6CO2 + 12H + 12 NADPH
What are the 3 most common fatty acids in the human body?
- steric acid (18 C)
- oleic acid (18 C)
- palmitic acid (16 C)
How are triglycerides absorbed from the intestinal lumen?
> Most triglycerides are digested into monoglycerides and fatty acid.
> Intestinal epithelial cells resynthesize these into triglycerides that enter the lymph as chylomicrons.
> Apoprotein B is adsorbed to the chylomicron surfaces.
How are chylomicrons transported to the venous system?
Via the thoracic duct.
What various tissues in the body remove chylomicrons?
> adipose tissue
skeletal muscle
heart
What tissues synthesize lipoprotein lipase?
- adipose tissue
- skeletal muscle
- heart
What does lipoprotein lipase do?
> is transported to surface of capillary epithelial cells
> hydrolyzes chylomicron triglycerides, releasing fatty acids and glycerol
What can fatty acids be used for?
Fuel or again synthesized into triglycerides.
What percentage of plasma fatty acids are replaced very 2-3 minutes?
50%
True or False:
All normal energy requirements of the body can be provided by the oxidation of fatty acids without using carbohydrates or proteins as an energy source.
True
What conditions increase utilization of fat for energy?
> starvation
> diabetes mellitus
Where are lipoproteins synethesized?
> by intestinal cells
-chylomicrons
> by liver
- VLDLs
- IDLs
- LDLs
- HDLs
What is the function of lipoproteins?
transport lipids in the blood
VLDL
> high concentration of triglycerides and moderate amounts of cholesterol and phospholipids
> transport lipids mainly from liver to adipose tissue
LDL
high concentration of cholesterol and moderate concentration of phospholipids
HDL
high concentration of proteins and low concentration of cholesterol and fatty acids
What two cell types don’t use fatty acids for energy?
- brain cells
- red blood cells
What are triglycerides hydrolyzed into?
fatty acids + glycerol
which are transported in blood to tissues
What are the principal functions of the liver in lipid metabolism?
1) degrade fatty acids into small compounds that can be used for energy
2) synthesize triglycerides, mainly from carbohydrates, but to a lesser extent from proteins too
3) synthesize other lipids from fatty acids, especially cholesterol and phospholipids
Under what conditions do large quantities of triglycerides appear in the liver?
1) during early stages of starvation
2) diabetes mellitus
3) in any other conditino in which fat instead of carbohydrates is being used for energy
in these conditions, large quantities of triglycerides are mobilized from the adipose tissue, transported as free fatty acids in the blood, and redeposited as triglycerides in the liver, where the initial stages of much of fat degradation begin
When triglycerides are hydrolyzed into fatty acids and glycerol, what is glycerol converted into?
glycerol-3-phosphate
Where are fatty acids converted to acetly-coa at?
mitochondria
Fatty acids are converted to acetyl-coa in the mitochondria.
> process = Beta-oxidation
Carnitine is used as a carrier molecule into the mitochondria
Acetyl-CoA enters the citric acid cycle by binding to oxaloacetic acid
hydrogens enter the chemiosmotic oxidative system
What are the products of beta-oxidation of one molecule of steric acid?
9 acetyl-CoA molecules
146 molecules of ATP
Degradation of fatty acids in the liver releases many acetyl-CoA’s not used for metabolism.
> 2 acetyl-CoA’s condense to form acetoacetic acid
> some of the acetoacetic acid is converted to:
- B-hydroxybutyric acid
- acetone
List the 3 ketone bodies we are covering.
> acetoacetic acid
Beta-hydroxybutyric acid
acetone
True of False:
Ketone bodies diffuse back into cells and are convert into acetyl-CoA.
True
What happens if the concentrations of ketone bodies increase above normal in the blood?
ketosis occurs
What conditions favor ketosis?
> starvation
diabetes
diet composed almost entirely of fat
How many step process is the synthesis of fatty acids?
2 step process
involves malonyl-CoA and NADPH
What is fat synthesis important?
> more fat can be stored in tissues than carbohydrates
> weight-for-weight, fat contains 2.5X the energy of carbohydrates
Explain why fats are poorly synthesized during insulin insufficiency.
1) when insulin is not available, glucose does not enter the fat and liver cells satisfactorily, so little of the acetly-CoA and NADPH needed for fat synthesis can be derived from glucose.
2) lack of glucose in the fat cells greatly reduces the availability of alpha-glycerophosphate, which also makes it difficult for the tissues to form triglycerides.
Explain why carbohydrates are preferred over fats for energy.
1) fats in adipose tissue cells are present in two forms - stored triglycerides and small quantities of free fatty acids. They are inconstant equilibrium with each other. When excess quantities of alpha-glycerophosphate are present (which occurs when excess carbohydrates are available), the excess alpha-glycerophosphate binds the free fatty acids in the form of stored triglycerides. As a result, the equilibrium between free fatty acids and triglycerides shifts toward the stored triglycerides; consequently, only minute quantities of fatty acids are available to be used for energy. Because alpha-glycerophosphate is an important product of glucose metabolism, the availability of large amounts of glucose automatically inhibits the use of fatty acids for energy.
2) when carbohydrates are available in excess, fatty acids are synthesized more rapidly than they are degraded. This effect is caused partially by the large quantities of acetyl-CoA formed from the carbohydrates and by the low concentration of free fatty acids in the adipose tissue, thus creating conditions appropriate for the conversion of acetyl-CoA into fatty acids.
Development of Atherosclerotic Plaque.
> damage to vascular endothelium
- increases the expression of adhesion molecules
- decreases release of NO andother substances that prevent adhesion of macromolecules and cells
circulating monocytes and LDLs accumulate at injury site
> monocytes - cross endothelium - enter intima - become macrophages > macrophages - ingest lipoproteins - become foam cells - form visible fatty streaks > fatty streaks - grow larger - coalesce > surrounding fibrous and smooth muscle tissues - proliferate - form large plaques
What can large plaques do?
> occlude lumen
become sclerotic or fibrotic
become calcified
What are the basic causes of atheroscelerosis?
> increased LDLs
> familial hypercholesterolemia (defective LDL receptor)
True or False:
HDLs may be able to absorb cholesterol crystals that are beginning to be deposited in arterial walls.
True
