cho after midterm Flashcards
what is glutathione
Glutathione is a tripeptide composed of glutamate, cystein, glycine. Reduced glutathione (GSH) maintains the normal reduced state of the cell.
Glutothione functions
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).
what does the enzyme glutathione reductase use
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.
Regulation of Blood Glucose
- 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) - other NB requirements for glucose:
a) lactose production in the mammary gland
b) main energy source for the fetus
UTILIZATION OF STORED CARBOHYDRATE
IN THE POST-ABSORPTIVE STATE
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]
- Glycogenolysis
pathway to glucose and enzyme
glycogen → glu 1-P → glu 6-P → glu
- enzyme phosphorylase → break
glycogen bonds
Remember Liver contains glucose 6-phosphatase.
• Muscle does not have this enzyme.
why?
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.
Allosterism
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
Epinephrine and Glucagon Stimulate
Glycogen breakdown
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.
Fed vs. Fast
glucagon vs insuling
Glucagon = starved state; stimulates glycogen breakdown, inhibits glycogen synthesis. • High blood glucose levels = fed state; insulin stimulates glycogen synthesis and inhibits glycogen breakdown.
Gluconeogenesis (GNG)
where does it happen
whate are the substrates (4)
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
Gluconeogenic enzymes (muscle/adipose lack
these):
glycolysis vs. GNG
Glycolysis Enzyme
Glucokinase
Phosphofructokinase-1
Pyruvate kinase
GNG Enzyme Glucose 6-phosphatase Fructose 1,6-bisphosphatase Phosphoenolpyruvate carboxykinase Pyruvate carboxylase (2 step reaction)
Pyruvate Carboxylase
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.
Phosphoenolpyruvate
Carboxykinase
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+
where is pyruvate carboxylated
Pyruvate is carboxylated in the mitochondria. by
Pyruvate Carboxylase
Oxaloacetate can’t pass out of
the mitochondria. and must become malate by malate DH
