CHEM 30B   Dr. R. Rinehart

CHAPTERS 23 & 22.7-22.9: 

 I.  Fat digestion, absorption, and transport 
         A.  Digestion: requires emulsification by bile salts and hydrolysis by pancreatic lipase
B.  Products: monoglycerides, diglycerides, fatty acids, glycerol
         C.  Absorbed as mixed micelles; triglycerides resynthesized in mucosal cells and packaged
as chylomicra; released into lymphatic circulation; eventually enter blood;
                  blood levels of TG peak ~4 hr after meal, remain elevated > 10 hrs        

D.  Plasma lipoproteins: classified by behavior when centrifuged [also by electrophoresis]                       

            CLASS à






diameter, Å





flotation constant

Sf > 400

Sf  20-400

Sf  0-20


density, g/mL





% triglyceride





% phospholipid





% cholesterol





% protein





apoprotein types

A-I, AII, 








where made


liver, intestine, blood




deliver dietary fat to muscle, heart, adipose tissues

deliver triglycerides & cholesterol

deliver cholesterol to other tissues

return cholesterol to liver


Defects in cholesterol and lipoprotein metabolism by Michael W. King at Indiana State U Medical School 

Heart and Stroke Encyclopedia by the American Heart Association®

             E.  Fat mobilization: epinephrine and other hormones stimulate  “hormone-sensitive lipase” in
adipose tissue; the resulting glycerol and “free” (unesterified) fatty acids enter the blood,
where the fatty acids are carried by serum albumin to muscle, heart, liver, kidney, etc.
Glycerol taken up by cells is converted to DHAP, which can then be catabolized by
                     glycolysis or used to yield glucose via gluconeogenesis

II.  Fatty acid oxidation [fats yield 9 kcal/g] 
         A.  Activation: further metabolism requires attachment to CoA -- this process
requires the equivalent of 2 ATP per fatty acid. This is a cytoplasmic reaction, but further
degradation of the fatty acid occurs in the mitochondrial matrix.  Transport of the fatty
                     acyl group across the mitochondrial inner membrane involves a carrier called carnitine,
                      a derivative of lysine, and two membrane-bound molecules of carnitine acyltransferase. 

            B.  Beta-oxidation is the major catabolic pathway for fatty acids. It is a pseudo-cyclic or “spiral”
pathway in which a sequence of four reactions is repeated until the entire molecule has
                      been split into acetyl-CoA. The pathway occurs in the mitochondrial matrix 

1.  Dehydrogenation of RCH2CH2CH2 CO~SCoA with FAD to give FADH2 and
RCH2CH=CHCO~SCoA  (a,b-unsaturated fatty acyl CoA). This reaction is
analogous to the succinate à fumarate reaction of the Krebs cycle. 

2.  Hydration of the a,b double bond to give a b-hydroxy fatty acyl CoA
RCH2CH=CHCO~SCoA  + H2O  à  RCH2CHOHCH2CO~SCoA. This reaction
is analogous to the fumarate à malate reaction of the Krebs cycle. 

3.  Dehydrogenation of the b 2o alcohol  with to give a b-ketoacyl CoA
Analogous to malate à oxaloacetate. 

4.  Cleavage of the first two carbons with HSCoA, yielding acetyl-CoA and a shorter 
        fatty acyl CoA
ready to go through the cycle again.
        RCH2COCH2CO~SCoA + HSCoA  à  RCH2CO~SCoA +  CH3CO~SCoA 

 The reactions of b-oxidation. Each cycle shortens the chain by 2C
Initial activation
   pyrophosphatase hydrolyzes PPi to 2 Pi, so net energy loss for this reaction is 2 ~

In the last cycle, butyryl-CoA
à 2 AcCoA. Hence, C2n à n AcCoA in (n-1) cycles
Each AcCoA gives 12 ATP from Krebs cycle and oxidative phosphorylation
Each cycle yields 1 NADH and 1 FADH2  or 5 ATP/cycle

overall process including Krebs cycle and oxidative phosphorylation:
C2nH4nO2  +   (3n-1) O2
à 2n CO2 + 2n H2O
, with net formation of (17n-7) ATP

                        5.  For a typical fatty acid containing 2n carbon atoms:
            n molecules of AcCoA are produced; 12n ATP after they go through the Krebs cycle;
            (n-1) cycles are required; each cycle produces one FADH2 and one NADH
            FADH2  yields 2 ATP and NADH yields 3 ATP  after electron transport
       The net energy yield for our C2n fatty acid is thus:
            12n  [AcCoA/Krebs+ETS]  +  5(n-1)  [ETS per cycle]   -  2 [activation rxn]
            or   17n – 7  ATP  [other books using lower ATP from ETS may state this as 14n-6] 

Errors in mitochondrial fatty acid oxidation by Michael W. King at Indiana State U School of Medicine

            C.  Ketogenesis:  under conditions of starvation, diabetes mellitus, or carbohydrate deprivation,
b-oxidation and amino acid oxidation increase.  In the liver, excess AcCoA  is converted
                        to acetoacetate,  a b-ketoacid which can be reduced with NADH to b-hydroxybutyrate;
                        Both of these molecules are water-soluble fuels for aerobic tissues (brain, heart, muscle)
However, they are also acids, and overproduction, as in diabetes, leads to “ketoacidosis”.
Excess acetoacetate gives rise to acetone via spontaneous decarboxylation; it is volatile
                        enough to be expelled by the lungs and can be detected in the exhalation of uncontrolled
                        diabetics. The three compounds (acetoacetate, b-hydroxybutyrate, acetone) are 
                        collectively known as
  “ketone bodies” . 
            [KB] > 20 mg%  =  ketonemia;   > 70 mg%
produces ketonuria
            ketosis  =  ketonemia + ketonuria + acetone breath

            ketoacidosis = ketosis with a plasma pH below 7.35; causes loss of minerals,
                        dehydration, coma, and death. 

            D.  Ethanol metabolism [I should have covered this when we did aerobic metabolism].
                        An aerobic process, occurs in the liver; net energy yield: 16 ATP/mole EtOH, 7 kcal/g

                    Ethanol catabolism increases the cellular NADH/NAD+ ratio, thus inhibiting glycolysis and
b-oxidation. As little as 6 weeks of heavy drinking causes fatty infiltration of the liver, which is
                     reversible in the early stages, but which can progress to irreversible cirrhosis of the liver. 
                    Prolonged heavy drinking also induces a "microsomal ethanol-oxidizing system" [MEOS],
                    which, although it does lead to an increased capacity to metabolize ethanol, causes other
                    alterations in liver metabolism that are also deleterious.

III.  Fatty acid synthesis: occurs in adipose tissue and liver when  carbohydrates are plentiful.
A.  Occurs in cytosol; uses a multienzyme fatty acid synthase complex with acyl carrier protein
B.  2C from AcCoA leave mitochondrial matrix as citrate and AcCoA is regenerated in cytosol
C.  Energy from ATP and reducing power from NADPH (a modified form of NADH produced in
                  the “pentose pathway”) and the vitamin biotin and CO2 are also required
D.  The actual reactions look pretty much like a reversal of  b-oxidation
E.  Newly-synthesized fatty acids are converted to triglycerides. 

PowerPoint slides on lipid, amino acid, drug, and alcohol metabolism by James Hardy at U Akron 
Lipid metabolism by James Blair at Oklahoma State 
Animations of fat digestion, cytoplasmic activation of fatty acids,
and transport across the inner mitochondrial membrane by carnitine

from Harcourt Brace, publishers of Interactive Biochemistry by Garrett & Grisham
Lipid metabolism by Michael W. King at Indiana State U Medical School 
Metabolic Pathways of Biochemistry by Karl J. Miller at George Washington U
  > Lipid Metabolism

IV.   Amino acid metabolism 
A.   Protein digestion and absorption
stomach: pepsin;  intestine: trypsin, chymotrypsin, carboxypeptidases, aminopeptidases,
                          elastase, di- and tri-peptidases. Absorption
is a complex process requiring a Na+ gradient and
an additional 3 ATP/AA;  as a result, the body will net 2.8 kcal/g instead of the theoretical 4-4.5 kcal/g

            B.  Amino acid pool: from diet, recovery of AA from degraded proteins, and synthesis (nonessential)
  ~75% of pool used for protein synthesis;  protein turnover:  continuous synthesis &
hydrolysis of body proteins; different proteins have different turnover rates.

            C.  Specialized products from amino acids:
TYR:  dopamine, norepinephrine, epinephrine, thyroxine, melanin
TRP:   serotonin, melatonin
            HIS:   histamine
SER:  ethanolamine, cephalins
CYS:  taurine,
b-mercaptoethylamine in HSCoA
LYS:  carnitine

GLY, TRP, MET, ARG, etc:  
                                    feed the “one-carbon pool” used in all sorts of processes including
            synthesis of  thymine, choline, carnitine, creatine, ……
a neurotransmitter
GLN:  NH3 for urine buffering, N donor for purine & pyrimidine synthesis
ASP:   converted to NMDA, a neurotransmitter

See more on specialized products from amino acids by Michael W. King at Indiana State U Medical School 

            D.   Catabolism: 20 AA with >1 pathway each; we’ll just hit the high points;  first, remove the
a-amino group by transamination and deamination and convert the nitrogen to urea;
then, transform the carbon skeleton to useful goodies like Krebs intermediates, glucose
                     and ketone bodies. Most steps occur in mitochondrial matrix of the liver

            E.   Transamination:  requires pyridoxal phosphate (a vit. B6 derivative) and a-KG or OAA (from
the Krebs cycle), yielding an a-keto carbon skeleton and GLU or ASP.

            E.   (Oxidative) deamination:  GLU + NAD+  à   aKG + NADH +  NH4+

            F.   The urea cycle converts CO2, NH4+ and the a-NH2 group of ASP to urea, a neutral water-
                    soluble molecule excreted in the urine. Net energy requirement 4 ATP / urea made
            Works in conjunction with the Krebs cycle

            G.  Carbon skeleton fates:
                        1.   If catabolism yields AcCoA and/or AcAcCoA, the amino acid is ketogenic

             ILE, LEU*, TRP, LYS, PHE, TYR are ketogenic  [* = exclusively ketogenic]

2.  If  catabolism yields Krebs intermediates and/ or pyruvate or other C3 compounds,
the amino acid is glucogenic [ = exclusively glucogenic]

            ALA†, GLY†, CYS†, SER†, THR, TRP, ASP†, ASN†, GLU†, GLN†, HIS†,
         PRO†, ARG†, ILE, MET†, VAL†, PHE, TYR, LYS

            H.  Biosynthesis of nonessential amino acids: usually glycolysis intermediates or Krebs intermediates
provide the C-skeleton and transamination delivers the N;  PHE à  TYR; defect in this
process causes phenylketonuria (PKU), a very serious inborn error of metabolism.

            I.   There are plenty of other, but much rarer, hereditary disorders of amino acid metabolism that
your book doesn’t mention!

See inborn disorders of amino acid metabolism by Michael W. King at Indiana State U Medical School
Nitrogen metabolism by Michael W. King at Indiana State U Medical School 
Amino acid metabolism [all 20 of 'em] by Michael W. King at Indiana State U Medical School 
Amino acid metabolism by James Blair at Oklahoma State U
and don't forget the ultimate: Biochemical Pathways from Boehringer Mannheim via ExPASy 

 © Ronald W. Rinehart, 2002-2007  Structures drawn with MDL IsisDraw®