cho after midterm

Question 1

what is glutathione

Answer 1

Glutathione is a
tripeptide composed
of glutamate,
cystein, glycine.
Reduced glutathione
(GSH) maintains the
normal reduced
state of the cell.

Question 2

Glutothione functions

Answer 2

It serves as a reductant.
• Conjugates to drugs making them
water soluble.
• Involved in amino acid transport
across cell membranes.
• Cofactor in some enzymatic
reactions.
– rearrangement of protein disulfide
bonds.
The sulfhydryl of GSH is used to reduce
peroxides (ROS) formed during oxygen
transport.
– Reactive oxygen species (ROS) damage
macromolecules (DNA, RNA, and protein)
and ultimately lead to cell death.
• The resulting oxidized form of GSH is
two molecules linked by a disulfide
bridge (GSSG).

Question 3

what does the enzyme glutathione reductase use

Answer 3

uses
NADPH as a
cofactor to reduce
GSSG back to two
moles of GSH.
Thus, the pentose
pathway is linked
to the supply of
adequate amounts
of GSH.

Question 4

Regulation of Blood Glucose

Answer 4

1. obligate glu users: cannot use FAs, AAs for nrg
   eg, brain, nervous tissue, RBCs, WBCs, renal
   medulla
   - need to maintain blood glu levels (therefore, control on lower
   limit [fasting level])
   eg, human, pig, horse: 4-5.5 mmol/L (70-100 mg/dL)
   cat, dog (carnivores): 3 mmol/L (~60 mg/dL)
   cow, sheep (ruminants): 1.5-2 mmol/L (~35-40 mg/dL)
2. other NB requirements for glucose:
   a) lactose production in the mammary gland
   b) main energy source for the fetus

Question 5

UTILIZATION OF STORED CARBOHYDRATE

IN THE POST-ABSORPTIVE STATE

Answer 5

blood glucose ↓ to below fasting level (regulation)
[↑ glucagon from α cells, Islets of Langerhan, pancreas]
↓
↓ glucose uptake into cells
↓
↑ glycogenolysis and gluconeogenesis
(↑ glucose output from liver)
[muscle glycogen breakdown, no response to ↑ glucagon]

Question 6

5. Glycogenolysis

pathway to glucose and enzyme

Answer 6

glycogen → glu 1-P → glu 6-P → glu
- enzyme phosphorylase → break
glycogen bonds

Question 7

Remember Liver contains glucose 6-phosphatase.
• Muscle does not have this enzyme.
why?

Answer 7

The liver releases glucose to the blood to be taken
up by brain and active muscle. The liver
regulates blood glucose levels.
The muscle retains glucose 6-phosphate to be use
for energy. Phosphorylated glucose is not
transported out of muscle cells.

Question 8

Allosterism

Answer 8

A change in the activity and conformation of an enzyme resulting from the binding of a compound at a site on the enzyme other than the active binding site

Question 9

Epinephrine and Glucagon Stimulate

Glycogen breakdown

Answer 9

Muscle is responsive to epinephrine.
• Liver is responsive to glucagon and
somewhat responsive to epinephrine.
• Both signal a cascade of molecular
events leading to glycogen breakdown.

Question 10

Fed vs. Fast

glucagon vs insuling

Answer 10

Glucagon = starved state; stimulates
glycogen breakdown, inhibits glycogen
synthesis.
• High blood glucose levels = fed state;
insulin stimulates glycogen synthesis and
inhibits glycogen breakdown.

Question 11

Gluconeogenesis (GNG)
where does it happen
whate are the substrates (4)

Answer 11

glycolysis in reverse (sort of ?)
- mainly in liver (kidney in starvation)
- Converts pyruvate and related three- and four-carbon
compounds to glucose
Substrates: glycerol
lactate (Cori cycle)
pyruvate
part (if not all) of C-skeleton of most AAs
(ie, loss of NH2 by trans- or de-amination)
Essentially reversal of glycolysis except
that three reactions in glycolytic sequence
are not reversible: reactions catalyzed by
glucokinase and hexokinase,
phosphfructokinase, and pyruvate kinase
- GNG requires these reactions to be
bypassed by other enzymes

Question 12

Gluconeogenic enzymes (muscle/adipose lack
these):
glycolysis vs. GNG

Answer 12

Glycolysis Enzyme
Glucokinase
Phosphofructokinase-1
Pyruvate kinase

GNG Enzyme
Glucose 6-phosphatase
Fructose 1,6-bisphosphatase
Phosphoenolpyruvate
carboxykinase
Pyruvate carboxylase
(2 step reaction)

Question 13

Pyruvate Carboxylase

Answer 13

Pyruvate + CO2 + ATP + H2O 
oxaloacetate + ADP + Pi + 2 H+
• Pyruvate Carboxylase fixes CO2
. Enzymes
which fix CO2
. require the cofactor
BIOTIN. Biotin is a vitamin and is always
involved in CO2
fixation.
• This reaction takes place in the
mitochondrial matrix.

Question 14

Phosphoenolpyruvate

Carboxykinase

Answer 14

Oxaloacetate + GTP 
phosphoenolpyruvate + GDP + CO2
• This reaction takes place in the cytosol
• PEP is now synthesized and the sum of
the two reaction is:
• Pyruvate + ATP + GTP + H2O 
PEP + ADP + GDP + Pi + H+

Question 15

where is pyruvate carboxylated

Answer 15

Pyruvate is carboxylated in the mitochondria. by
Pyruvate Carboxylase

Oxaloacetate can’t pass out of
the mitochondria. and must become malate by malate DH

Question 16

what happens to oxaloacetate in the cytosol

Answer 16

Oxaloacetate decarboxylated and
phosphorylated in the cytosol. by
Phosphoenolpyruvate Carboxykinase

Question 17

Cori cycle

Answer 17

Cori cycle (removal of muscle lactate)
muscle lactate → blood → liver lactate → glu
Lactate from active muscle is converted to glucose in liver.

Question 18

Acetyl CoA

Answer 18

Acetyl CoA (or Cs from metabolite converted to acetyl
CoA, eg, FAs) cannot form net glucose
-2 Cs enter TCA at acetyl CoA
-2 CO2
lost with each turn of TCA

Question 19

what are the obligate glucose users

Answer 19

brain, nervous tissue, RBCs, WBCs, renal

medulla

Question 20

biotin where is it used

Answer 20

Biotin is a vitamin and is always
involved in CO2
fixation. is a cofactor in pyruvate carboxylase

Question 21

The importance of gluconeogenesis

Answer 21

Liver glycogen, in absence of CHO intake, lasts for 16h (in the human)
After this period, animal solely dependent on liver GNG to maintain
blood glucose
eg, prolonged fasting, nearly “0” CHO diet

Question 22

Anaerobic Glycolysis during

Intensive Exercise

Answer 22

glu / glycogen → pyruvate → lactate
• anaerobic, no O2
(in cytosol)
Intensive muscle exercise:
1. Up to 100x ATP requirement of resting or low-activity
- ATP generation is major limiting factor for
maintaining intensive activity
2. Lack of sufficient O2 to sustain e- transport chain
3. ATP derived from substrate-generated glycolysis
(glycogen, glucose)
4. Muscle anaerobic glycolysis “kept going” by:
a) lactate production
b) the Cori cycle
5. Stimulus to glycogenolysis is epinephrine (adrenal
medulla)
6. In muscle: glycogen → 2 lactate (yields 3 ATP / 6Cs)
glucose → 2 lactate (yields 2 ATP / 6Cs)
In liver: 2 lactate → glucose costs 6 ATP

Question 23

Anaerobic Glycolysis during
Intensive Exercise (Con’t)
in muscle, in liver

Answer 23

6. In muscle: glycogen → 2 lactate (yields 3 ATP / 6Cs)
   glucose → 2 lactate (yields 2 ATP / 6Cs)
   In liver: 2 lactate → glucose costs 6 ATP

Question 24

Acetate is not

Answer 24

glucogenic
Remember: Acetate is never converted
to glucose in animals.
Acetate in not glucogenic.
The free energy (ΔG°’=-33.4kJ/mol) derived
from the oxidative decarboxylation of pyruvate
is large.
The pyruvate DH reaction essentially
irreversible

Question 25

TOPICS RELATED TO | UTILIZATION OF CHO

Answer 25

1. Lactose Intolerance - lack / relative lack of digestive enzyme lactase - genetic versus acquired Lactose remains in small intestine: a. osmotic effect b. attacked by bacteria → lactic acid (irritant) → methane & H2 (bloating) c. symptoms: diarrhea, nausea, vomiting CHO 2. Zero Carbohydrate Diet for Weight Reduction (like Atkins, Zone, South Beach) - very restrictive food choices → nutrient deprivation - produces mild ketosis (reduces appetite) Risks: - ↑ risk of gout, osteoporosis, heart disease ? - produces dehydration 3. Glycogen Loading - used by athletes involved in endurance sports - can ↑ time of maximum performance 2 fold - reason: as 75-90% max O2 capacity reached, muscle metabolism → anaerobic

Question 26

Strategies to maximize glycogen stores

Answer 26

1. Consume a high carbohydrate diet on a daily basis 2. Take in sources of glucose during exercise - Beverages or foods 3. Carbohydrate loading – Days 7-4 before competition: moderate carbohydrate intake with training 1-2 hours per day – Days 3-1: high carbohydrate intake with limited training – Consuming a high carbohydrate meal within two hours after exercise has also been shown to increase muscle glycogen by 300%

Question 27

Strategies to maximize glycogen stores | Risks:

Answer 27

a. ↑ body wt / feeling of heaviness, stiff muscles b. accentuated hypoglycemia follows depletion of large glycogen load

Question 28

CHO TOPICS | 4. High Fibre Diets for Weight Control

Answer 28

- normal, desirable intake: 20-30 g/d If some is good, is more better? a. Hypothesis: ↑ fibre in food, ↑ satiety, ↓ energy density b. Properties of fibre in GI tract: i. attracts / holds H2O (pectins gums) → ↓ transit time ii. provides bulk (cellulose)→ stimulates peristalsis iii. binds cholesterol & bile acids (lignin, gums, pectins) iv. phytic acid found with fibre in seeds / grains binds divalent cations (Ca, Mg, Zn, Fe) v. bacteria in gut can attack fibre (energy source)

Question 29

5. Diabetes Mellitus

Answer 29

anomaly in carbohydrate metabolism

Question 30

6. Oral Health (Dental Caries)

Answer 30

free sugars | - DRI position on free sugars

Question 31

7. Galactose and Fructose Intolerance

Answer 31

- inborn error of metabolism - galactosaemia: mental retardation / cataracts in infants (avoid milk)

Question 32

8. Hepatic Glycogen-Storage Diseases (Glycogenoses)

Answer 32

``` - genetic disorders in carbohydrate metabolism LIVER: Type I - von Gierke's disease Type III - Cori's disease Type IV - Andersen's disease Type VI - Hers' disease MUSCLE: Type II - Pompe's disease Type V - McArdle's disease Type VII Type VIII ```

Question 33

Von Gierke Disease

Answer 33

Edgar Otto Conrad von Gierke, German pathologist,1877-1945 • Hereditary metabolic disorder with autosomal recessive inheritance • Due to an inborn lack of glucose-6-phosphatase • Consequently, glucose 6-phosphate can not be converted to glucose • This results in low blood sugar - hypoglycemia ``` Without glucose-6-phosphatase: • Levels of glucose 6-phosphate increase – Glycolysis increases • Levels of lactate and pyruvate in blood increase – Glycogen levels increase • Glycogen is deposited in liver and kidney cells. A child who has Von Gierke disease, would have an enlarged liver -- hepatomegaly. Treatment • Prevent hypoglycemia with frequent feedings of foods of high starch foods (broken down to glucose) •Avoid CHO that must be converted to G6P to be utilized (fructose and galactose) ```

Question 34

Pompe Disease | J.C. Pompe, 20th century Dutch pathologist

Answer 34

``` Autosomal recessive inheritance • Due to an inborn lack of alpha-1,4 glucosidase (acid maltase), an enzyme which cleaves 1,4 and 1,6 alpha-glycosidic linkages. • Absence of this enzyme leads to an accumulation of glycogen in lysosomes. ``` • Organs affected by accumulation of glycogen – skeletal muscles (mostly), CNS, heart, liver, • leading to: – bulky muscles including macroglossia (enlarged tongue) and cardiomegaly (enlarged heart) – hypotonia (loss of muscle tone) and muscle weakness, including congestive heart failure (from heart muscle weakness)

Question 35

McArdle Disease | Cori’s type V glycogenosis

Answer 35

Results from a defect in muscle glycogen phosphorylaseB . • More than 30 known mutations can produce the same clinical picture (phenotype). • In about half of patients, there is a single base change (R49X) in which the codon for Arg becomes a stop codon, resulting in a partially completed non-functional protein. • The remaining mutations are a mixture of nonsense (stop codons) and missense (changed amino acid) mutations that result in incorrect folding and/or loss of catalytic activity. Glycogen phosphorylase activity is lost. Notice the difference between normal pattern dark staining for phosphorylase (figure A) compared to the lack of dark staining (except in a few blood vessels) in a patient with McArdle disease (figure B). Occasional vacuoles are filled with glycogen (asterisks in figure C) since glycogen can not be broken down to glucose. • During normal exercise, O2 can not be transported to muscles cells fast enough. Thus, a stored reserve of glucose (glycogen) is used as fuel. • Since glycogen can not be broken down to glucose in patients with McArdle disease, lactate does not build up. • After several minutes of exercise, patients experience severe muscle pain, probably from increased ADP.

Question 36

McArdle Disease | Symptoms:

Answer 36

- muscular pain - fatigability - muscle cramping following exercise, which disappears with rest - later in life - severe cramps and myoglobinuria after exercise. - kidney failure can be associated with rhabdomyolysis (muscle breakdown)