LIPID METABOLISM

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LIPID METABOLISM BLOOD LIPIDS

• During digestion, lipids are hydrolyzed to
  glycerol, fatty acids, and monoglycerides.
• For transport in the lymph and blood, the cells
  of the small intestines produce lipoprotein
  aggregates called chylomicrons.

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LIPID METABOLISM BLOOD LIPIDS (continued)

• Behavior of blood lipids parallels that of blood
  sugar.
• The concentrations of both increase after a meal.
• The concentrations of both return to normal as a
  result of
• storage in fat depots.
• oxidation to provide energy.
• Plasma lipids concentrations
• rise within 2 hours of a meal.
• reach a peak in 4-6 hours.
• drop rapidly to a normal level.

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BLOOD LIPID CLASSIFICATION

• Lipids are less dense than proteins.
• The classification of blood lipids is based on
  density.
• The higher the lipid concentration of a
  lipoprotein aggregate, the lower the density.

VLDL very low density lipoprotein LDL low
density lipoprotein HDL high density
lipoprotein
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SCHEMATIC MODEL OF LDL
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FAT MOBILIZATION (continued)

• Fatty acids stored in triglycerides are called on
  as energy sources
• after a few hours of fasting.
• even when glycogen supplies are adequate by
  resting muscle and liver cells, because it
• conserves the bodys glycogen stores and glucose
  for brain cells and red blood cells.
• Brain cells do not obtain nutrients from blood.
• Red blood cells do not have mitochondria
  therefore, red blood cells do not have fatty acid
  oxidation.

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FAT MOBILIZATION (continued)

• Triglycerides are stored in adipose tissue.
• Several hormones, including epinephrine,
  stimulate fat mobilization when body cells need
  fatty acids for energy.
• Fat mobilization entails the hydrolysis of stored
  triglycerides into fatty acids and glycerol which
  then enter the bloodstream.
• In blood, mobilized fatty acids form a
  lipoprotein with the plasma protein called serum
  albumin.
• Fatty acids transported to tissue cells that need
  them in this form.
• Glycerol produced from triglyceride hydrolysis is
  water soluble.
• Glycerol dissolves in blood.
• Glycerol is transported to cells that need it.

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GLYCEROL METABOLISM

• Glycerol can be converted to dihydroxyacetone
  phosphate, an intermediate of glycolysis.
• Glycerol can be converted to pyruvate and
  contribute to cellular energy production.
• Pyruvate can be converted to glucose through
  gluconeogenesis.

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FATTY ACID OXIDATION

• Activation Step
• Before fatty acids can be catabolized, they must
  be activated by conversion to fatty acyl CoA.
  
• The conversion to fatty acyl CoA is catalyzed by
  acyl CoA synthetase.

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FATTY ACID OXIDATION (continued)

• After activation, the fatty acid enters
  mitochondria and is degraded in the fatty acid
  spiral via ?-oxidation.
• In the final step of ?-oxidation, the chain is
  broken between the ?- and ?-carbons by the
  reaction with coenzyme A.

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FATTY ACID OXIDATION (continued)
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FATTY ACID OXIDATION (continued)
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FATTY ACID OXIDATION (continued)

• Stearic acid
• makes eight passes through ?-oxidation sequence.
• produces nine molecules of acetyl CoA.
• produces eight molecules FADH2.
• produces eight molecules of NADH.

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FATTY ACID OXIDATION (continued)

• During ?-oxidation, the second carbon of the
  fatty acyl CoA molecule is oxidized to a ketone.
• Each pass through the fatty acid spiral produces
• one molecule acetyl CoA
• one molecule NADH
• and one molecule FADH2.

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FATTY ACID OXIDATION (continued)

• In the last spiral, the four-carbon chain of
  butyryl CoA passed through the ?-oxidation
  sequence, and produces
• one molecule FADH2,
• one molecule NADH,
• and two molecules of acetyl CoA.

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KEY NUMBERS FOR ATP CALCULATIONS

• Determine the number of acetyl CoA molecules
• Determine the number of trips through the fatty
  acid spiral (one less than the number of acetyl
  CoA molecules)
• Multipliers
• every acetyl CoA 10 ATP molecules
• every NADH 2.5 ATP molecules
• every FADH2 1.5 ATP molecules

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KEY NUMBERS FOR ATP CALCULATIONS (continued)

• Example for 10-carbon fatty acid (five acetyl CoA
  molecules, four trips through fatty acid spiral)

(5 acetyl CoA) 10 50 ATP (4 NADH H) 2.5
10 ATP (4 FADH2) 1.5 6 ATP Activation
step -2 ATP Total ATP 64 ATP
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ENERGY FROM FATTY ACIDS

• To obtain energy from stearic acid
• it is activated by a reaction with coenzyme A to
  form stearoyl CoA, which requires the hydrolysis
  of ATP to AMP and PPi and PPi to 2 Pi
• stearoyl CoA passes through the ?-oxidation
  spiral to form
• 9 molecules of acetyl CoA, which can enter citric
  acid cycle and electron transport chain to
  produce 10 ATP molecules per acetyl CoA
• 8 molecules FADH2, which can enter the electron
  transport chain to produce 1.5 ATP molecules per
  FADH2
• and 8 molecules NADH, which can enter the
  electron transport chain to produce 2.5 ATP
  molecules per NADH
• One molecule of stearic acid yields 120 molecules
  of ATP upon complete degredation.

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ENERGY FROM FATTY ACIDS (continued)

• The amount of energy produced from stearic acid
  (C18)

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ENERGY FROM FATTY ACIDS (continued)

• Fatty acids are more energy dense than
  carbohydrates.
• On basis of equal numbers of carbons, lipids are
  nearly 25 more efficient than carbohydrates as
  energy-storage systems.
• On an equal-mass basis, lipids contain more than
  twice the energy of carbohydrates.
• Lipids are more reduced than glucose (partially
  oxidized).

Compound Mass ATP Produced
1 mol stearic acid (C18) 284g 120 mol
3 mol glucose (C18) 540g 96 mol
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AMINO ACID METABOLISM

• The most important function of amino acids
• is to provide building blocks for the synthesis
  of proteins in the body.
• uses 75 of amino acids in normal, healthy
  adults.
• The amino acid pool is the total supply of amino
  acids in the body coming from digestion of food,
  degradation of tissue, and synthesis in the
  liver.
• Protein turnover is when body proteins are
  hydrolyzed and resynthesized.
• Turnover rate of proteins is measured as a
  half-life.
• Amino acids in excess of immediate body
  requirements are not stored for later use, but
  degraded and the nitrogen atoms are converted and
  excreted, while carbon skeletons are used for
  energy production, synthesis of glucose, or
  conversion to triglycerides.

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AMINO ACID METABOLISM (continued)
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AMINO ACID METABOLISM (continued)
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AMINO ACID CATABOLISM

• The nitrogen of amino acids is either excreted or
  used to synthesize other compounds.
• There are three stages to nitrogen
  catabolism 1. Transamination 2.
  Deamination 3. Urea formation

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AMINO ACID CATABOLISM (continued)

• Step 1 Transamination is the enzyme-catalyzed
  (transaminase) transfer of an amino group to a
  keto acid.
• This process is also an important method in the
  biosynthesis of nonessential amino acids
  (glutamate and aspartate) from a variety of amino
  acids.

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AMINO ACID CATABOLISM (continued)

• The following equations are specific examples of
  the transfer of amino groups to ?-ketoglutarate.
  The carbon skeleton remains behind and is
  transformed into a new ?-keto acid

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AMINO ACID CATABOLISM (continued)

• Step 2 Deamination is an oxidative process
  resulting in a removal of an amino group.
• This reaction is the principle source of NH4 in
  humans.
• This reaction is called oxidative deamination.
• This reaction is catalyzed by enzymes in the
  liver (amino acid oxidases).

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AMINO ACID CATABOLISM (continued)

• Step 3 Urea Formation via a metabolic pathway
  (urea cycle) in which ammonia is converted to
  urea.

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UREA CYCLE
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UREA CYCLE (continued)

• After urea is formed, it diffuses out of liver
  cells into the blood, the kidneys filter it out,
  and it is excreted in the urine.
• Normal urine from an adult contains 25-30 g of
  urea daily, but exact amount varies with protein
  content of the diet.
• The direct excretion of NH4 accounts for a small
  but important amount of the total urinary
  nitrogen.
• It can be excreted with acidic ions, which helps
  kidneys control the acid-base balance of body
  fluids.

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FATE OF THE CARBON SKELETON

• The carbon skeletons of amino acids fall into two
  categories
• glucogenic amino acids, which have a carbon
  skeleton that can be metabolically converted to
  an intermediate of glucose synthesis.
• ketogenic amino acids, which have a carbon
  skeleton that can be metabolically converted to
  acetyl CoA or acetoacetyl CoA.

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AMINO ACID CATABOLISM (continued)

• The fates of ketogenic (green) amino acid carbon
  skeletons and glucogenic (purple) amino acids

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ESSENTIAL AND NONESSENTIAL AMINO ACIDS

• Note Essential amino acids cannot be
  synthesized by the body nonessential amino acids
  can be synthesized by the body.

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AMINO ACID BIOSYNTHESIS

• A summary of amino acid biosynthesis

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AMINO ACID BIOSYNTHESIS (continued)

• The liver produces most of the amino acids the
  body can synthesize (nonessential amino acids).
• The synthesis occurs from intermediates of the
  glycolysis pathway and citric acid cycle.
• Tryosine is produced from the essential amino
  acid phenylalanine

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AMINO ACID BIOSYNTHESIS (continued)

• Glutamate, alanine, and aspartate are synthesized
  from ?-keto acids via reactions catalyzed by
  transaminases.
• Alanine is produced from pyruvate and glutamate

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AMINO ACID BIOSYNTHESIS (continued)

• Asparagine and glutamine are formed from
  aspartate and glutamate by reaction of the
  side-chain carboxylate groups with ammonium ions