CARBOHYDRATE METABOLISM

CARBOHYDRATE DIGESTION FATES OF PYRUVATE

GENERATED BY GLYCOLYSIS
1. Mouth
Salivary a-Amylase – Hydrolysis of some
Aerobic conditions (Humans, animals, micro)
a-glycosidic linkages
= Acetyl CoA (goes to Krebs)
2. Stomach
Anaerobic conditions (Humans, animals, micro)
Gastric juice – No effect on digestion
= Lactate (recycling of NADH)
3. Small intestine
Anaerobic conditions (microorganisms)
Pancreatic digestive enzymes – Hydrolysis of
= Ethanol (Beer and wine)
polysaccharides to disaccharides.

FERMENTATION PROCESS
4. Intestinal mucosal cells
Is a biochemical process by which NADH is
Maltase, Sucrase, Lactase - Hydrolysis of
oxidized to NAD+ without the need for oxygen.
disaccharides into monosaccharides.

5. Intestinal lining – Active transport of sugars ANAEROBIC LACTATE FORMATION

to bloodstream.

ENZYMES IN CARBOHYDRATE DIGESTION

Salivary a-Amylase – Catalyzes the hydrolysis of
a-glycosidic linkages in starch.

Pancreatic a-amylase – Breaks down

polysaccharide into shorter segments.

Maltase, Sucrase, & Lactase – Enzyme involved

in the final step in carbohydrate digestion.

The Substance needed for monosaccharides to

enter the bloodstream = ATP

GLYCOLYSIS
 The metabolic pathway by which
glucose is converted into 2 PYRUVATE,
and NADH-.
 Pyruvate – Chemical energy in the form
of atp.
 NADH – Reduced coenzymes.
GLYCOLYSIS
1. HEXOKINASE (Glucose)
Glucose 6-Phosphate
2. PHOSPOGLUCOISOMERASE
Fructose 6-Phosphate
3. PHOSPOFRUCTOKINASE
Fructose 1,6-BisPhosphate
PENTOSE PHOSPHATE PATHWAY
4. ALDOLASE
Is the pathway by which glucose 6-phosphate is
Glyceraldehyde 3-Phosphate (G3P)
used to produce NADPH, ribose 5-phosphate
Dehydroxyacetone phosphate (DHAP)
and numerous other sugar phosphate

5. G3P  ISOMERASE
GOAL OF PPP
 Synthesis of the coenzyme NADPH
6. TRIOSE PHOSPHATE DEHYDROGENASE
needed in lipid biosynthesis
1,3-BisPhosphoGlycerate
 Production of ribose 5-Phosphate
IMPORTANCE OF PPP
7. PHOSPOGYLCEROKINASE
 When ATP demand is high, Pathway
3-Phospoglycerate
continues to its end product.
 When NADPH demand is high,
8. PHOSPOGLYCEROMUTASE
intermediates are recycled into glucose
2-Phospogylycerate
6-phosphate
 When ribose 5-phosphate demand is
9. ENOLASE
high, most of the nonoxidative stage is
Phosphoenolpyruvate (PEP)
nonfunctional

10. PYRUVATE KINASE

B VITAMINS AND THEIR COENZYMES
Pyruvate
Vitamins Coenzyme (or just keywords)
Vit. B1 Thiamin Thiamin pyrophosphate (TPP)
GLYCOGEN SYNTHESIS AND DEGRADATION
Vit. B2 Riboflavin Flavin (FMN & FAD)
Vit. B3 Nicotinic acid Nicotinamide (NAD1 & NADP1)
Glycogenolysis = Glycogen -> Glucose
Vit. B5 Pantothenic acid Coenzyme A (CoA)
Vit. B6 Pyridoxine Pyridoxal (PLP, PNP, PMP)
Glycolysis = Glucose -> Pyruvate
Vit. B7 Biotin Biotin
Vit. B9 Folic acid Tetrahydrofolate (THF)
Gluconeogenesis = Pyruvate -> Glucose
Vit. B12 Methylcobalamine
Cyanocobalamin
Glycogenesis = Glucose -> Glycogen
CELLULAR RESPIRATION  Takes place in cytoplasm
chemical process that releases energy from  Anaerobic (Doesn’t Use Oxygen)
organic compounds (food), gradually converting  Requires input of 2 ATP
it into energy that is stored in ATP molecules  Glucose split into two molecules of
pyruvate
Involves three stages:  Also produces 2 NADH and 4 ATP
 Glycolysis
 Krebs cycle Formation of Acetyl CoA
 Electron Transport Chain 1. Junction between glycolysis and Krebs cycle
2. Oxidation of pyruvate to acetyl CoA
What is ATP? 3. Pyruvate molecules are translocated from
 Adenosine Triphosphate the cytosol into the mitochondrion by a
 Energy used by all cells carrier protein in the mitochondrial
 Organic molecule containing high-energy membrane
Phosphate bonds 4. A CO2 is removed from pyruvate – making a
2-carbon compound.
What does ATP do for you? 5. Coenzyme A is attached to the acetyl group.
It supplies YOU with ENERGY

By breaking the high-energy bonds between the

last two phosphates in ATP

Where Does Cellular Respiration Take Place?

in two parts of the cell:
 Glycolysis occurs in the Cytoplasm
 Krebs Cycle & ETC take place in the
Mitochondria

GLYCOLYSIS
1. Means “splitting of sugar” CITRIC ACID CYCLE (KREBS CYCLE)
2. occurs in the cytosol of the cell  Requires Oxygen (aerobic)
3. Partially oxidizes glucose (6C) into pyruvate  Turns twice per glucose molecule
(3C) molecules.  Produces 2 ATP
4. Occurs whether or not oxygen is present  Takes place in matrix of mitochondria

GLYCOLYSIS SUMMARY Pyruvate – Pyruvate dehydrogenase – Acetyl CoA

 3. Process produces 34 ATP or 90% of the ATP
in the body
4. Requires oxygen, the final electron acceptor
5. Every FADH2 = 2 ATP
6. Every NADH = 3 ATP
MNEMONICS 7. Chemiosmosis – The production of ATP
Citrate Citrate using the energy H+ gradients across
Is Isocitrate membranes to phosphorylate ADP
A a-ketoglutarate
Starting Succinyl CoA ETP FRIENDS
Substance Succinate Complex I (NADH Supplier)
For Fumarate NADH dehydrogenase
Making Malate
Oxaloacetate Oxaloacetate Complex II (FADH supplier) (no blowhole)
Succinate dehydrogenase
Enzymes
Citrate Synthase Citrate Complex III
Aconitase Isocitrate Cytochrome bc1
Isocitrate dehydrogenase a-ketoglutarate
a-ketoglutarate dehydrogenase succinyl CoA Complex IV
Succinyl CoA Synthetase Succinate Cytochrome c oxidase
Succinate dehydrogenase fumarate
Fumarase Malate ATP Synthase
Malate dehydrogenase Oxaloacetate  a protein in the inner membrane in the
mitochondria
KREB CYCLE SUMMARY  Uses energy of the ion gradient to
 Each turn of Krebs cycle also produces power ATP synthesis
3NADH, 1 FADH2, and 2CO2  For every H+ ion that flows through ATP
 Therefore, for each glucose molecule, the synthase, one ATP can be formed from
Krebs cycle produces 6NADH, 2FADH2, 4CO2, ADP
and 2ATP (Cuz its done twice)

ELECTRON TRANSPORT CHAIN LIPID METABOLISM

1. Located in the inner membrane of the Fatty acids – Are taken up by cells.
mitochondria They serve as:
2. Oxygen pulls the electrons from NADH and  Precursors in synthesis of other
FADH2 down the electron transport chain to compounds.
a lower energy state  Fuels for energy production
 Substrates for ketone body synthesis
  Digestion in the Stomach: causes a
TAG DIGESTION large physical change: - Churned into
1. Mouth droplets (Chyme)
Saliva – No effect on digestion  Chyme – Thick semi-liquid material
made up of partially digested food and
2. Stomach gastric secretions.
Churning Action – produces small fat
droplets (chyme) Gastric Lipase:
Gastric Lipases – Hydrolyze some (10%) Hydrolysis of lipids occurs
TAGS.  Chyme triggers cholecystokinin (CCK) to
release bile from gallbladder.
3. Small Intestine
Bile – Solubilizes “droplets” Pancreatic Lipase: Hydrolyze ester linkages
Pancreatic lipases – Produce between glycerol and Fatty acids units of TAGS
monoacylglycerols, which form fatty
acid micelles. MICELLES
Oil droplets will form spherical micelle shapes.
4. Intestinal cells – Micelles “repacked” Bile salts aid this process, clumping fatty acids
into TAGS, which form chylomicrons. and monoacylglycerols.
Chylomicrons – Bus of TAGS that
transport them to the lymphatic Micelles are small enough to penetrate
system. membrane of intestinal cells.

5. Lymphatic system – Transport TAGs to

CHYLOMICRONS
bloodstream.
TAGS are combined with membrane and water-
soluble proteins to form a chylomicron, a
6. Bloodstream – TAGS are hydrolyzed to
lipoprotein.
free fatty acids.

Chylomicrons carry TAGS from intestinal cells

into the bloodstream via the lymph system.

DIGESTION AND ABSORPTION OF

LIPIDS TAGS IN BLOODSTREAM
 98% of ingested lipids are Triacylglycerols reach the bloodstream and are
triacylglycerols (TAGS) hydrolyzed down to glycerol and fatty acids.
 Digestion in the Mouth: enzymes are
aqueous These are absorbed by cells and processed
further for energy by forming acetyl CoA.
or of acyl CoA into the mitochondrial
Stored as lipids in fat cells (adipose tissue) matrix.
TRIACYLGLYCEROL STORAGE AND
MOBILIZATION BETA OXIDATION PATHWAY
 Adipocytes are specialized cells that  Repetitive series of four biochemical
contain TAGS reactions that degrades acyl CoA to
 Adipose tissue contains large number acetyl CoA by removing two carbon
of adipocyte cells. atoms at a time
Adipocytes are found mostly in the abdominal  Produces FADH2 and NADH
and subcutaneous tissue.
They are used to store energy, insulation, and 1. Oxidation: Acyl CoA -> trans-Enoyl CoA
shock absorber for organs. Enzyme: Acyl CoA dehydrogenase
Adipocytes are metabolically very active
(Constantly hydrolyzed and re-synthesized) 2. Hydration:
trans-Enoyl CoA -> L-B-Hydroxyacyl CoA
OXIDATION OF FATTY ACIDS Enzyme: Enoyl CoA Hydratase
There are three parts to the process by which
fatty acids are broken down to obtain energy. 3. Oxidation:
1. The fatty acid must be Activated by L-B-Hydroxyacyl CoA -> B-Ketoacyl CoA
bonding to coenzyme A. Enzyme:
2. The fatty acid must be Transported into B-Hydroxyacyl CoA dehydrogenase
the mitochondrial matrix by a shuttle
mechanism. 4. Chain Cleavage:
3. The fatty acid must be repeatedly B-Ketoacyl CoA -> Acetyl CoA
Oxidized, cycling through a series of Enzyme: Thiolase
four reactions, to produce acetyl CoA,
FADH2, and NADH. Number of acetyl CoA is half of the total
FATTY ACID ACTIVATION carbons
 Fatty acid is converted to a high-energy
derivative of coenzyme A Number of repetitive sequences is one
 Site: mitochondria less than the number of acetyl CoA

Ex.
C18 FA – 9 Acetyl CoA – 8 RSequence
C14 FA – 7 Acetyl CoA – 6 RSequence
FATTY ACID TRANSPORT
 Fatty acids are transported across the BOP FOR UNSATURATED FATTY
inner mitochondrial membrane in the ACIDS
form of acyl carnitine
 A shuttle mechanism involving the D-B-Hydroxyacyl CoA -> L-B-Hydroxyacyl CoA
molecule carnitine effects the transport Enzyme: Epimerase
 3. The liver uses fatty acids as the
Cis-(3,4) -> Trans-(2,3) preferred fuel.
Enzyme: Cis-trans isomerase 4. The brain function is maintained by
glucose and ketone. Fatty acids cannot
BETA OXIDATION PATHWAY cross the blood-brain barrier and thus
 The acetyl CoA produced enters the are unavailable.
CITRIC ACID CYCLE
 The FADH2 and NADH+ enter the KETONE BODIES
respiratory system  Sufficient oxaloacetate must be present
for the acetyl CoA to react with.
FATTY ACID VS GLUCOSE OXIDATION  Oxaloacetate concentration depends on
pyruvate produced from glycolysis
COMPARISON ON ATP PRODUCTION
 When oxaloacetate supplies are too low
for all acetyl CoA to be processed
through the TCA cycle, ketogenesis
takes place.
 Ketogenesis – Excess acetyl CoA is
converted to ketone bodies.
 Synthesis of ketone bodies for acetyl
CoA is primarily in liver mitochondria.
 The three ketone bodies produced are:
Acetoacetic acid, B -hydroxybutyric
acid, and acetone

Ketosis – The overall accumulation of ketone

bodies in the blood and in urine.

Ketonemia – in the blood

Ketonuria – in the urine
KETOGENESIS
1. First Condensation
2 Acetyl CoA ->
Acetoacetyl CoA
Enzyme: Thiolase

2. Second Condensation
PREFERRED FUEL OF HUMAN BODY
Acetoacetyl CoA +
1. Skeletal muscle uses glucose when in
Acetyl CoA
active state. Fatty acids in resting state.
-> HMG-CoA
2. Cardiac muscle depends first on fatty
Enzyme: HMG-CoA
acids, and secondarily on ketone
Synthase
bodies, glucose, and lactate.
 - Dehydration: Water is removed from
3. Chain Cleavage alcohol to form an alkene
HMG-CoA -> Acetoacetate + Acetyl CoA - Hydrogenation: Hydrogen is added to
Enzyme: HMG CoA Lyase alkene 3 to form saturated butyryl ACP
from NADPH
4. Reduction
Acetoacetate -> B-Hydroxybutyrate
Enzyme: CHOLESTEROL
B-Hydroxybutyrate dehydrogenase  Secondary component of cell
membrane
LIPOGENESIS VS FA DEGRADATION  Precursor for bile salts, sex hormones,
and adrenal hormone.
 Acetyl CoA is the starting material for  synthesis of cholesterol occur in liver.
lipogenesis
 Acetyl CoA needed for lipogenesis is FATE OF FATTY-ACID GENERATED
generated in mitochondria, therefore it ACETYL CoA
must first be transported to the cytosol. Acety-CoA formed from fatty acids is further
 Citrate-malate transport system helps channeled in various different routes:
transport acetyl CoA to cytosol - Oxidation in the citric acid cycle: both
lipids and carbohydrates supply acetyl
CoA
- Ketone body formation: Very
important when imbalance between
carbohydrate and lipid metabolism
- Fatty acid biosynthesis: the buildup of
excess acetyl CoA when dietary intake
exceeds energy needs leads to
indirectly. accelerated fatty acid biosynthesis.
- Cholesterol biosynthesis: It occurs
when the body is in an acetyl CoA rich
state.

CHAIN ELONGATION PROTEIN

Four reactions constitute the steps of chain
 Not stored in the human body, they are
elongation process
constantly broken down in to their
- Condensation: Acetyl-ACP and malonyl-
constituent amino acids and then reused for
ACP condense together to form
protein synthesis.
Acetoacetyl-ACP
 Overall turn-over in adult man is equivalent
- Hydrogenation: The keto group of the
to replacement of 1-2% of the body protein
Acetoacetyl complex is reduced to
each day
alcohol to form by NADPH
 Degradation (catabolism of AA) = excess Protein turnover – Is the breakdown and re-
AA (amino acids) are not stored! But rapidly synthesis of body protein.
degraded for the synthesis of glucose and  Old tissue
lipids. Degradation of excess AA causes an  Damage
excess of nitrogen.  Recycling enzyme and hormones
 Waste = Nitrogen excess is transformed
into urea (80%) and ammonium (NH4+) in PROTEIN DIGESTION AND ABSORPTION
order to be thrown away in the urine. (Liver 1. Mouth:
and blood) Saliva – no effect on digestion

PROTEIN DIGESTION 2. Stomach:

 Protein breakdown begins in the HCl – denatures protein
stomach. Pepsin – Hydrolyzes peptide bonds
 No protein hydrolyzing enzymes are
found in saliva. 3. Small intestine:
Hydrolyze peptide bonds of large
Hydrolysis (10% of peptide bonds) and polypeptides
denaturation by pepsin enzyme & HCL acid  Trypsin
produce short chain polypeptides In the  Chymotrypsin
stomach.  Carboxypeptidase
 Aminopeptidase
ENZYMES THAT HYDROLYZE PEPTIDE BONDS
1. Trypsin (Pancreatic enzyme) 4. intestinal Lining:
2. Chymotrypsin (Pancreatic enzyme) Active transport of amino acids to the
3. Carboxypeptidase bloodstream.
4. Aminopeptidase

Polypeptides = 10 – 100
Oligopeptides = 1 – 10

Free amino acids are absorbed through

intestinal wall via active transport.

The total supply of free amino acids available is

called: The Amino Acid Pool

3 sources of “free” amino acids:

1. Dietary protein breakdown
2. Biosynthesis of amino acids in the liver
3. Protein turnover
TRANSAMINATION AND OXIDATIVE TRANSAMINATION
Some transaminases are used for diagnosing
DEAMINATION
disorders:
Enzyme: Alanine aminotransferase
- escapes in large amounts from dead or
dying liver tissue.
- measured in blood samples

Alanine + Oxoglutarate = Pyruvate + Glutamate

Enzyme: Aspartate aminotransferase

- Very active inside heart cells
- also escapes in large amounts from
dead or dying heart tissue and enters
bloodstream
- measured in blood

Aspartate + Oxoglutarate = Oxaloacetate +

Release of amino group is also two steps. Glutamate
1. Transamination
2. Oxidative deamination TRANS-DEAMINATION (SUM IT UP)
Most transaminases share a common substrate
and product (oxoglutarate and glutamate) with
AMINO ACIDS: the enzyme glutamate dehydrogenase.
Glutamate, Aspartate, Alanine, Glutamine
Glutamate has a central role in the overall
present in higher concentrations in
control of nitrogen metabolism.
mammalian cells. Have metabolic functions
as well as roles in proteins.
OXIDATIVE DEAMINATION
The glutamate produced from the
Glutamate is the most important, transamination step is then deaminated by
metabolically. oxidative deamination using the enzyme
glutamate dehydrogenase:

Glutamate dehydrogenase
Glutamate -> a-ketoglutarate
a-ketoglutarate -> Glutamate
UREA CYCLE ALTERNATIVE METHODS OF NITROGEN
- +
Ammonium salts (NH ) are toxic
4 EXCRETION
compounds - Aquatic species excrete free ammonia
- Oxidative deamination is an easily through gills.
shifted equilibrium reaction. - Terrestrial critters produce urea
- The inputs to the urea cycle are NH3, - Spiders excrete guanine
and CO2, and aspartic acid and ATP. - Reptiles and birds excrete uric acid
- The outputs are urea, ADP, and fumaric
acid. PROGESSING AMINO ACID CARBON
SKELETONS
Glucogenic Amino Acids – Amino acid C
NH3 skeletons that degrade to form a Krebs cycle
Urea
CO2 intermediate.
ADP
Aspartic acid Ketogenic Amino Acids – Amino acid C
Fumaric acid
ATP Skeletons that degrade to form acetyl CoA or
Acetoacetyl CoA.

THE FOUR-STEP UREA CYCLE 20 AMINO ACIDS

Carbamoyl phosphate is converted to urea 2 are ketogenic: Leucine and Lysine
9 are glucogenic
1. TRANSFER 9 are both
Carbamoyl phosphate
Ornithine -> Citrulline 11 non-essential amino acids.
Enzyme: Ornithine transcarbomoylase
PHENYLKETONURIA (PKU)
2. Condensation - Defective phenylalanine hydroxylase –
Citrulline -> Arginosuccinate phenylalanine accumulates in body.
Enzyme: Argininosuccinate synthase - leads to severe mental retardation in
infants.
3. Cleavage
Arginosuccinate -> Arginine HEMOGLOBIN CATABOLISM
Enzyme: Argininosuccinate lyase - Globin – Protein part of blood
- Heme – Non-protein group
4. Hydrolysis Heme contains four pyrrole (tetrapyrrole)
Arginine -> Ornithine groups held together by an iron atom.
Enzyme: Arginase
Ferritin – Iron atom stored in a protein
Fumarate from urea cycle enters Krebs cycle.
Bilirubin – major antioxidant in blood
Aspartate produced from oxaloacetate of the Stercobilin – bilirubin excreted via poop
Krebs cycle enters the urea cycle. Urobilin – bilirubin excreted via urine
Jaundice – when bilirubin accumulates in the
blood. Spleen is degrading heme, but liver isn’t
removing the products.

COLOR OF BRUISE
Green -Biliverdin
Red – Bilirubin