• When daily nitrogen intake is equivilant to daily nitrogen loses.

• Result of a DNA point mutation (snip) causing glutamic acid to be replaced by valine
• More altered configuration of Hb molecule - low oxygen carrying capacity
• Morphology and function of RBC affected by Hb polymerization and formation of sickled cells (stick together to form long rigid rods)
• Cycle of sickling and reversal until > irreversibly sickled cells (ISC)
• Greater vaso-occlusion in small and large blood vessels
• ISCs are fragile, constantly hemolyzed and destroyed
• Greater low life span of RBC
• All organs of body affected (hypoxia)

Patients with sickle cell have this.

•  
  •  
    • Shorter, leaner, than normal
    • BMI much lower
    • Adolescent growth was retarded (low testosterone)
    • Bone density of wrist of HbSS (left) lower, bone age ~12 years
    • Seems like PEM is a part of the HbSS syndrome
    • All organs of the body and immune status affected

• Dietary protein.
• Digested in stomach by small intestine by Gastric and Pancreatic and Intestinal enzymes.
• Need all enzymes to complete digestion
• Free amino acids enter portal vein.

Pepsinogen→ Pepsin (H+)

Trypsinogen→ Trypsin (enteropeptidase)

Trypsinogen→ Trypsin (trypsin)

Chemotrypsinogen→ Chemotrypsin (trypsin)

Proelastase→ Elastase (trypsin)

Procarboxypeptidase→ Carboxypeptidase

• Genetic lack of pancratic enzymes.
• Protein mal-absorption
• Bulky foil smelling oily stools.
• Poor growth and mal-nutrition
• Similiar symptoms for pancreatitis and pancreatic
• treat with oral pancreatic enzymes.

• Gets in the cell through a Na cotransporter.
• Gets from the cell to the Portal Vein through AA specific facilitated transporters. Also have neutral ones that can transport many things.

• Common genetic error of AA transport.
• Poor reabsorption of cystein (arg, lys, + orn)
• Cystein precipitates to form kidney stones that block the urine tract, causes bleeding, and severe pain.
• Treat with large water intake and alkaline drugs to increase urin pH.

• relatively rare genetic error in AA transport.
• Defective transport of neutral AA.
• Loss of Tryptophan (precursor of niacin)
• Pellegra-like rash and some neurological symptoms.
• Treat with niacin.

Fate of absorbed amino acids?

57% oxidized in the liver

23% pass through liver intact to muscle.(branched chain neutral AA)

14% to synthesis of liver proteins

6 % to synthesis of plasma proteins.

-excess AA not stored. It is rapidly degraded.

Glutamate dehydrogenase reaction. And regulation of it.

• α-ketoglutarate binds free NH₄+ and becomes Glutamate.
• NADPH is used in the reaction.
• Only α-ketoglutarate and glutamate bind NH₄+
• Forward reaction is stimulated by ATP and GTP
• Backward reaction is stimulated by ADP and GDP
• this reaction Transfers NH₄+

• Liberation of amino group as free ammonia.
• The reverse part of the Glutamate Dehydrogenase reaction.

• Glutamate reacts with NH₄ to produce Glutamine.
• Requires ATP
• 50% of NH₄+ is transferred as Glutamine.

• The reversal of Glutamine synthase reaction.
• Glutamine + H20 → Glutamate + NH₃
• Free ammonium will be excreted in urin

• Transfers amino group from Amino Acid → α-Keto Acid.
• Happens at the beginning of every synthesis and breakdown of an Amino Acid 

Pyruvate + Glutamate→ Alanine + α-ketoglutamate

• Alanine is the main glucogenic substrate.

Oxaloacetate + Glutamate→ Aspartate + α-ketoglutamate

later on Aspartate→ Asparagine

Valine

Leucine

Isoleucine

Phenylalynine

Valine

Threonine

Tryptophan

Isoleucine

Methionine

Histadine

Arginine*

Leucine

Lysine

Leucine

Lysine

Phenylalynine

Isoleucine

Tryptophan

Threonine

Tyrosine

Asparagine

Aspartate

Glutamate

-Glutamine

-Proline

-Arginine

-Histidine

• Use Histidine
• will have a build up of FIGLU which is an intermediate before it is converted to Glutamate.

Propionyl CoA

-Isoleucine

-Methionine

-Threonine

-Valine

Phenylalanine

Tyrosine

Tryptophan

Isoleucine

Leucine

Threonine

Leucine

Lysine

Phenlyalanine

Tyrosine

Tryptophan

Alanine

Cysteine

Glycine

Hydroxyproline

Serine

Threonine

Tryptophan