Ch. 24 - Lipid and Amino Acid Metabolism

Lipid Metabolism

During digestion:

• Triglycerides are hydrolyzed to glycerol, fatty acids, and monoglycerides

• Phosphoglycerides are hydrolyzed to their component substances

Triglycerides and phosphoglycerides are resynthesized in…

the cells of intestinal mucosa

Chylomicron

are lipoproteins formed from the combination of insoluble lipids and proteins

• made for the transport of insoluble lipids within the lymph and blood

• Modified by the liver into smaller lipoprotein particles

Behavior of Blood and Plasma Lipids

Behavior of blood lipids parallels the behavior of blood sugar

Concentration of Blood Lipids and Blood Sugar

• Increases after a meal

• Returns to normal as a result of storage in fat depots and oxidation to provide energy

Concentration of Plasma Lipids:

• Rises within 2 hours of a meal

• peaks in 4–6 hours

• Drops rapidly to a normal level

Classification of Lipoproteins

Based on density

• Lipids are less dense than proteins

• Higher the lipid concentration of a lipoprotein, the lower the density

• VLDL - Very low density lipoprotein

• LDL - Low density lipoprotein

• HDL - High density lipoprotein

Energy from Fat Mobilization

When the body’s stores of glycogen are depleted, fatty acids are used as energy sources

• Helps conserve glycogen storage and glucose for:

  • Brain cells, which cannot directly obtain nutrients from the blood because of the blood-brain barrier

  • RBCs, which do not have mitochondria and therefore cannot oxidize fatty acids

• When body cells need fatty acids for energy, the endocrine system produces hormones that interact with adipose tissue

Fat Mobilization

Hydrolysis of stored triglycerides, followed by the entry of fatty acids and glycerol into the bloodstream

• In blood, mobilized fatty acids form a lipoprotein with the plasma protein called serum albumin and are transported to tissue cells in this form

Is glycerol water soluble or insoluble?

Glycerol is water-soluble

• Dissolves in blood and is transported to cells that need it

Glycerol Metabolism

Glycerol is converted in the cytoplasm to dihydroxyacetone phosphate, a chemical needed for glycolysis

• By entering glycolysis, glycerol can be converted to pyruvate and can help in cellular energy production

Oxidation of Fatty Acids: Step 1

Before fatty acids can be catabolized, they must be activated

• Activation involves converting from fatty acid to fatty acyl CoA

  • catalyzed by acyl CoA synthetase

• Energy is provided by the hydrolysis of ATP to AMP and PPi and the hydrolysis of PPi to 2Pi

Oxidation of Fatty Acids: Step 2

After activation, the fatty acyl CoA molecules that enter the mitochondria are degraded in the fatty acid spiral by β-oxidation

• the second (beta) carbon is oxidized to a ketone

Oxidation of Fatty Acids: Step 3

then, the chain is broken between the α- and β-carbons by the reaction with coenzyme A

• produces a new fatty acyl CoA and an acetyl CoA

Oxidation of Fatty Acids: Step 4

New fatty acyl compound enters the β-oxidation process at step 1

• Sequence is repeated until the fatty acyl CoA is completely degraded to acetyl CoA

• β-oxidation pathway is called the fatty acid spiral

  • Each pass through the fatty acid spiral reduces the fatty acyl CoA by 2 carbons and produces one molecule each of acetyl CoA, NADH, and FADH 2

Breakdown of Stearic Acid

Requires eight passes through the β-oxidation sequence

• Produces:

  • 9 molecules of acetyl CoA

  • 8 molecules of FADH2

  • 8 molecules of NADH

Energy from Fatty Acids

• Energy of fatty acids is more dense than carbs

• lipids are nearly 25% more efficient than carbs as energy-storage systems

• lipids contain more than twice the energy of carbs

• Lipids are a more reduced form of energy compared to glucose, which is partially oxidized

Ketone Bodies

Created in the liver when excess acetyl CoA is produced by fatty acid oxidation than can be processed by the citric acid cycle

• During a fast, the amount of glycolysis decreases and less oxaloacetate is synthesized

• Lack of oxaloacetate reduces the activity of CAC

• Includes acetoacetate, β-hydroxybutyrate, and acetone

• Carried by the blood to body tissues where they are oxidized to

  meet energy needs

• concentration of ketone bodies in the blood averages at 0.5 mg/100mL

Ketonemia

Presence of elevated level of ketone bodies (higher than 20 mg/100 mL) in the blood

Ketonuria

Presence of ketone bodies in the urine

• Occurs at a level of about 70 mg/100 mL when the renal threshold for ketones is exceeded and ketone bodies are excreted

Acetone Breath

Condition in which acetone can be detected in the breath

Ketosis

Condition in which ketonemia, ketonuria, and acetone breath exist together

• Can lead to a condition called ketoacidosis, where blood pH lowers because of elevated levels of ketone bodies

Treatment of Conditions Related to Ketone Bodies

• Diabetes-related ketosis can be treated with insulin

  • Insulin restores normal glucose metabolism and reduces the rate of formation of ketone bodies

• Ketosis accompanied by severe dehydration is treated by administering intravenous solutions that contain sodium bicarbonate

  • Returns fluid and acid–base balance

Number of acetyl CoA molecules can be determined using:

Number of trips through the fatty acid spiral can be determined using:

number of trips = molecules NADH = molecules FADH

• number of trips is also one less than the number of acetyl CoA molecules

Every acetyl CoA =

10 ATP

Every NADH =

2.5 ATP

Every FADH2 =

1.5 ATP

Summary for a 10-carbon fatty acid:

Fatty Acid Synthesis versus Fatty Acid

Degradation

These 2 pathways are not simply the reverse of each other

• Degradation occurs in the mitochondria

• Biosynthesis occurs in the cytoplasm

• Both processes require units of 2 carbon atoms from acetyl CoA, which is made in the mitochondria and must be transported to the cytoplasm for biosynthesis

• Transportation occurs by reacting acetyl CoA with oxaloacetate

acetyl CoA + oxaloacetate + H2O → citrate + CoA — SΗ

• Citrate reacts to regenerate acetyl CoA and oxaloacetate once in the cytoplasm

Fatty Acid Synthesis

• Occurs by a series of reactions that are catalyzed by fatty acid synthetase system

  • Made up of six enzymes and acyl carrier protein (ACP)

• After synthesis, the fatty acids are incorporated into triglycerides and stored in fat in adipose tissues

• Some plants and bacteria possess enzymes to convert fats to carbs as part of their normal metabolism

Liver in Fatty Acid Synthesis

The liver modifies body fats by lengthening or shortening and saturating or unsaturating fatty acid chains

Can the human body synthesize polyunsaturated fatty acids?

No, the human body cannot synthesize polyunsaturated fatty acids

• but it can convert linoleic acid and linolenic acid from the diet into other polyunsaturated fatty acids

Can the human body convert glucose to fatty acids?

Yes, it can convert glucose to fatty acids

• Cannot convert fatty acids to glucose

Amino Acid Metabolism

About 75% of amino acids in normal, healthy adults are used to provide building blocks for the synthesis of proteins

• Amino acid pool is continually used for the synthesis of other nitrogen-containing biomolecules

• Amino acids in excess are not stored for later use, they are degraded

Amino Acid Pool

Total supply of amino acids in the body

• comes from:

  • the digestion of food

  • the body’s own degraded tissue

  • the synthesis of some amino acids in the liver

Protein Turnover

Continuing process in which body proteins are

hydrolyzed and resynthesized

• Rate is expressed as a half-life

• Frequent turnover rate enables the body to:

  • Continually renew important molecules

  • Respond quickly to its own changing needs

Amino Acid Catabolism

Nitrogen of amino acids is either excreted or used to synthesize other compounds

• Stages in nitrogen catabolism

  • Transamination

  • Deamination

  • Urea formation

Stage 1 - Transamination

• transfer of an amino group to a keto acid

  • Influenced by transaminases

• In the transfer of amino groups to α-ketoglutarate, the carbon skeleton remains behind and is transformed into a new α-keto acid

• Key reactions

  • Transfer of amino groups to α-ketoglutarate to form a new α-keto acid

  • Production of aspartate

Stage 2 - Deamination

• Removal of NH3+

• Uses the glutamate produced in Stage 1

  • Glutamate dehydrogenase catalyzes the removal of the amino group from an ammonium ion and regenerates α-ketoglutarate

• main source of NH4+ in humans

Oxidative Deamination

Reactions are catalyzed by amino acid oxidases found in the liver

Stage 3 - Urea Formation

• Urea cycle takes place

  • Metabolic pathway where ammonium ions are converted to urea

  • Processes NH4+ in the form of carbamoyl phosphate, which is made in the mitochondria from ammonium ions and bicarbonate ions

• uses 2 ATP

Urea Cycle

After urea is formed, it diffuses out of liver cells into the blood, kidneys filter it out, and it is excreted in the urine

• Normal urine from an adult contains 25–30 g of urea daily

  • Exact amount varies with protein content of the diet

• Direct excretion of NH4+ accounts for a small but important amount of the total urinary nitrogen

  • NH4+ can be excreted with acidic ions, which help kidneys control the acid–base balance of body fluids

Fate of the Carbon Skeleton

Once a carbon skeleton is catabolized into pyruvate, it has two possible uses

• Production of energy

• Synthesis of glucose

Glucogenic Amino Acids

• Have carbon skeletons that can be metabolically converted to materials used in glucose synthesis

• Helps synthesize glucose through gluconeogenesis after glycogen stores are used up

Ketogenic Amino Acids

Have carbon skeletons that can be metabolically converted to acetyl CoA or acetoacetyl CoA

Amino Acid Biosynthesis

Nonessential amino acids can be synthesized by the body

• Initiated by components of the glycolysis pathway and citric acid cycle

• Glutamate, alanine, and aspartate are synthesized from α-keto acids via reactions catalyzed by transaminases

  • Helps adjust proportions of amino acids to meet the body’s needs by taking part in biosynthesis

  • Alanine is produced from pyruvate and glutamate

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

Amino Acid Biosynthesis Cont.