protein metabolism. protein digestion protein breakdown begins in the stomach. no protein...

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Protein Metabolism

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Page 1: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Protein Metabolism

Page 2: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Protein DigestionProtein breakdown begins in the stomach.

No protein hydrolyzing enzymes are found in saliva.

Hydrolysis (10% of peptide bonds) & denaturization by pepsin enzyme & HCl acid produce short chain polypeptides in the stomach.

Trypsin, chymotrypsin, & carboxypeptidasefrom Pancreatic juices,

and Aminopeptidase from cells in the small intestine Brush Zone create “free” amino acids.

Page 3: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Free amino acids are absorbed thru intestinal wall via active transport.

Enter bloodstream and are brought to cells.

The total supply of free amino acids available is called: the Amino Acid Pool.

3 sources of “free” amino acids:1. Dietary protein breakdown2. Biosynthesis of amino acids in the Liver3. Protein turnover (I prefer apple turnovers)

Protein turnover is the breakdown & re-synthesis of body protein:• Old tissues• Damage• Recycling enzymes & hormones

Page 4: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Summary of protein digestion in the human body.Possible fates for amino acid

degradation products.

Page 5: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Transamination and Oxidative Deamination:

Two steps in degrading amino acids1) remove -amino group2) breakdown & process carbon skeleton

Release of an amino group is also two steps:1) Transamination2) Oxidative deamination

Page 6: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Central role of glutamate:Amino acids:

Glutamate, aspartate, alanine & glutamine present in higher concentrations in mammalian cells. Have metabolic functions as well as roles in proteins.

Glutamate is the most important, metabolically.

Page 7: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Some transaminases are used for diagnosing disorders:enzyme alanine aminotransferase

Escapes in large amounts from dead or dying liver tissue. Measured in blood samples for diagnostic purposes.

Page 8: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Transaminase enzyme aspartate aminotransferase very active enzyme inside heart cells.

Also escapes in large amounts from dead or dying heart tissues & enters bloodstream.

Measured in blood for diagnosing myocardial infarction.

Page 9: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Trans-deamination (sum it up)Most transaminases share a common substrate and product (oxoglutarate and glutamate) with the

enzyme glutamate dehydrogenase.

This permits a combined N excretion pathway for individual amino acids: "trans-deamination.”

Glutamate has a central role in the overall control of nitrogen metabolism.

a.k.a.-ketoglutarate

Page 10: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Oxidative DeaminationThe glutamate produced from the transamination

step is then deaminated by oxidative deamination using the enzyme glutamate dehydrogenase:

And away I go!

Recycles back to a ketodiacid & releases ammonia

Page 11: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Glutamate dehydrogenase [GluDH] will reversibly convert

glutamate to -ketoglutarate and -ketoglutarate to glutamate.

Deamination reaction

uses NAD+ reverse reaction uses NADPH

Uses both NAD+ and NADPH – how to regulate it?

Page 12: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Urea cycle:Urea cycle:Ammonium salts (NH4

+) are toxic compounds.

Oxidative deamination converting glutamate to -ketoglutarate is an easily shifted

equilibrium reaction.

Ammonium ions building up favors the synthesis of excessive amounts of glutamate,

decreasing the Krebs cycle intermediate

-ketoglutarate.

This in turn decreases ATP production, and that affects the nervous system.

The answer is Urea:

Page 13: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

The inputs to the urea cycle are NH3, CO2 and aspartic acid and ATP.

The outputs are urea, ADP and fumaric acid.

The carbonyl group of urea is derived from CO2 Ammonia contributes one of the amine groups on urea

Page 14: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

The four-step urea cycle in which carbamoyl phosphate is converted to urea.

Page 15: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

The nitrogen content of the various compounds that participate in the urea cycle.

Does it remind you of the

Krebs cycle in any way?

Page 16: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Fumarate from the urea cycle enters the Krebs cycle. Aspartate produced from oxaloacetate of

the Krebs cycle enters the urea cycle.

Oxaloacetate has 4 potential fates: transamination; conversion to glucose; formation of citrate; conversion to pyruvate

Page 17: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Summary:Transamination takes off amine groups from amino acids and forms

glutamate (ionized glutamic acid)

Amine groups form ammonia when removed

in deamination

This combines with CO2 & Aspartate.

Forms ureaurea, Arginine,& Fumarate

Page 18: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Alternative methods of nitrogen excretionAquatic species excrete free ammonia through gills. Terrestrial critters produce Urea - very soluble - still

needs water for removal via kidneys. Imposes a minimum daily water requirement.

Spiders excrete guanine, 5 nitrogen atoms in a small molecule.

Page 19: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Reptiles & birds excrete uric acid – very insoluble purine compound – forms supersaturated solutions. Concentrated urine, supersaturated with uric acid,

goes from cloaca into hindgut – uric acid crystalizes & water is reabsorbed.

In humans uric acid deposits crystals & causes gout.

Page 20: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Processing Amino Acid Carbon SkeletonsTransamination or Oxidative deamination both

produce -keto acidsDegradation of these carbon skeletons may take several

different pathways:

Amino acid C skeletons that degrade to form a Krebs cycle intermediate can then be used to make glucose

via gluconeogenesis. These are called Glucogenic Amino Acids.

Amino acid C skeletons that degrade to form acetyl CoA or Acetoacetyl CoA

can form fatty acids or ketone bodies. These are called Ketogenic Amino Acids.

Page 21: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

F ates of C skeletons of 20 amino acids. Two are ketogenic: leucine &

lysine.Nine are

glucogenic.Nine are

both because they

form pyruvate or have two different

degradation products.

Page 22: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Amino Acid Biosynthesis

Essential amino acids can be made by plants & bacteria in 7 to 10 steps.

We obtain these amino acids by eating plants.

11 Non-essential amino acids synthesized in 1 to 3 steps.

Use glycolysis intermediates:3-phosphoglycerate & pyruvate

Krebs cycle intermediates:Oxaloacetate & -ketoglutarate

Page 23: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Starting materials for biosynthesis of 11 nonessential amino acids: 1 step, 2 steps, or 3 steps

Alanine, aspartate, & glutamate use transamination

Page 24: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Phenylalanine & tyrosine degradation:Degradation of phenylalanine starts with conversion to tyrosine catalyzed by phenylalanine hydroxylase.Fumarate & acetoacetate are formed. Fumarate is converted to oxaloacetate for TCA cycle & acetoacetate is converted to acetyl CoA.

Page 25: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Phenylketonuria (PKU): Defective phenylalanine hydroxylase – phenylalanine accumulates in body.

Phenylalanine is transaminated to phenylpyruvate.Accumulation of phenylpyruvate leads to severe

mental retardation in infants.Persons suffering from phenylketonuria should not

consume foods containing high levels of phenylalanine, such as aspartame.

Page 26: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Hemoglobin catabolism

Red blood cells contain oxygen carrying pigments of a conjugated protein:Protein part is Globin

Non-protein prosthetic group is HemeHeme contains four pyrrole (tetrapyrrole) groups

held together by an iron atom

Old red blood cells degraded in the spleen.Globin is hydrolyzed into amino acids.Iron atom stored in a protein (ferritin)

Tetrapyrrole degraded to bile pigments

Page 27: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Formation of Bile Pigments

Heme BiliverdinUses molecular O2, loses

1 C as CO which fuses to 1% of

hemoglobin.Fe3+ grabbed by ferritin to make new hemoglobin

Ring opens up

Page 28: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Central methylene bridge of Biliverdin is

reduced creating Bilirubin.

Bilirubin found to be the major antioxidant in

blood

Page 29: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Bilirubin transported to liver. Becomes more water soluble with attachment of glucoronide sugars to propionate side chains.

(Glucose + COO- group attached to 6th C)

Solubilized bilirubin is excreted in Bile.

Page 30: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Intestinal bacteria help change Bilirubin into Stercobilin and urobilinurobilin for excretion.

Page 31: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Jaundice: when bilirubin accumulates in the blood. Spleen is degrading heme, but liver isn’t removing the products.

Changing color of a bruise shows dominant degradation

product of heme: either biliverdin or bilirubin

Page 32: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Follow each

pathway to its various products.All are highly inter-

related.

Page 33: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

ATP production

Page 34: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

The human body’s response to feasting.

Page 35: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

The human body’s response to fasting

Remember: the Brain uses Glucose or Ketone bodies for fuel.

Page 36: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

The human body’s response to starvation

Everything is used to feed the brain Glucose or Ketone bodies.

Page 37: Protein Metabolism. Protein Digestion Protein breakdown begins in the stomach. No protein hydrolyzing enzymes are found in saliva. Hydrolysis (10% of

Review: can you…• Describe the steps in Protein digestion & absorption• Explain how Amino Acids are utilized in the body• Explain Transamination and Oxidative De-amination • Describe The Urea Cycle – purpose and steps• Describe how a.a. Carbon Skeletons are processed • Define and explain Amino Acid Biosynthesis.• Describe the chemical composition of urine.• Explain the relationship and importance of Arginine, Citrulline, and Nitric Oxide. • Give a detailed description of Hemoglobin Catabolism • Give an overview of the interrelationships among Carbohydrate, Lipid, and Protein Metabolic Pathways.