2012-11-26 1&2: Intro to Carbs; Glycolysis in RBCs Flashcards
What f(x)s do carbs serve?
1) metab fuel, 2) protein components, 3) RNA/DNA components, 4) structure in plants, 4)
Which form of glucose is transported in the blood?
99% is cyclized; alpha-D-glucose is major (2/3) form
Is it glucose and oxidizing or reducing sugar? When is this important? What would the metab product be useful for?
it is a reducing sugar (i.e. it reduces other things will becoming OXIDATED itself); makes glucuronic acid which detoxifies things like heme by conjugating them
How does hyperglycemia cause neuro- and retin-opathy?
- Glucose—aldose reductase—>sorbitol
- lens, retina, kidney and nerve cells lack sorbitol DH
- sorbitol builds up—>cataracts, periph neurop, retinop, nephrop
Which of the following is NOT true regarding glucose?
a. It spontaneously forms a cyclic, hemiacetal in solution.
b. It is a diastereoisomer of ribulose.
c. It is the form in which carbohydrate is transported from the liver to skeletal muscle.
d. It reacts chemically to form a covalent bond! with hemoglogin.
B
What can glucose be metabolized to in humans?
lactate, CO2, pentoses or glycogen
What does the heart do with lactate?
sends it thru CAC to make ATP
What does liver do with lactate?
converts it to glucose via gluconeogenesis
What is made with the pentose phosphate pathway?
pentoses, NADPH, and ATP
Where does pentose phosphate pathway occur?
in RBCs
Which pathway(s) of glucose metab is(are) anaerobic?
glycolysis and pentose phosphate pathway
How can RBCs use glucose
glycolysis and pentose phosphate pathway ONLY
How and where do we make fructose?
glucose—reduced to alcohol—>sorbitol—oxidized—>fructose; occurs in seminal vesicles and liver
How is HbA1c formed?
glucose slowly reacts with NH2 groups on Hb
GAGs vs. proteoglycans
GAGs = glycosaminoglycans = polysaccs w/ carboxy, amino and sulfate groups (e.g. chondroitin, heparin, hyaluronic acid, keratan sulfate)
proteoglycans are proteins with GAGs added onto them; form joint lubes and c.t.
Which glycosidic linkages can humans digest? Not?
We can: α-1,4 glycosidic bond
We can’t digest: ß-1,4, glycosidic bonds (e.g. cellulose)
What is the first step glucose undergoes upon entering the cell?
glucose—>G6P
What is the next step for G6P headed to glycolysis?
G6P—>F6P
What is the next step for G6P headed to glycogen synthesis?
G6P—>G1P
What is the next step for G6P headed to pentose phosphate pathway?
6-phosphogluconate
Why phosphorylate glucose?
Phosphorylation of glucose lowers its intracellular concentration and promotes glucose influx.
Why do RBCs need ATP?
to maintain membrane potential w/ Na/K ATPase
How many ATP/glucose in glycolysis?
2
Which enzymes regulate glycolysis?
hexokinase, phosphofructokinase-1 and pyruvate kinase
What is the overall formula for anaerobic glycolysis in an RBC?
glucose + 2 ADP + 2Pi —> 2 lactate + 2 ATP
Where is glucokinase present?
liver and pancreas
Which has a higher Km, glucokinase or hexokinase? What does that mean?
Glucose kinase’s Km (10mM) is 100X higher than hexokinase; allows pancreatic ß cells to sense glucose amt AND high vMax allows it to allow liver to take up high amts of blood glucose
What inhibits hexokinase?
G6P
Draw glycolysis with important enzymes!
- glucose—gluco-/hexo-kinase—>G6P
- G-6-P—>F-6-P
- F-6-P—PFK-1—>F-1,6-BP
- F-1,6-BP—>G3P (and DHAP)
- G3P—>1,3-BPG
- 1,3,-BPG—>2-PG
- 2-PG—>3-PG
- 3-PG—>PEP
- PEP—>pyruvate kinase—>pyruvate
- pyruvate—LHD—>lactate
What regulates PFK-1?
stimulated by: AMP, ADP, and F-2,6-BP
inhibited by: ATP, citrate
What regulates pyruvate kinase?
inhibited by: glucagon, ATP
How is glucokinase regulated?
It’s not? at least it’s not inhibited by G6P like hexokinase is
What are the steps involved in insulin secretion?
- Glucose enters pancreatic ß cell via GLUT-2
- gluc—glucokinase—>G6P
- resultant higher ATP closes ATP-sensitive K+ channel
- K+ can no longer leak out, and the resulting depolarization opens Ca2+ channel
- incr intracell Ca causes exocytosis of insulin granules
Which steps of glycolysis are NOT reversible?
- glucose—gluco- or hexo-kinase—>G6P
- F6P—PFK-1—>F1,6BP
- PEP—pyruvate kinase—>pyruvate
(i. e. the steps w/ the important enzymes)
What is the deal w/ PFK-2?
PFK-2 is bifunctional with kinase and phosphatase sides
kinase side does: F6P—>F-2,6-BP
F-2,6-P activates PFK-1
inhibited by glucagon (via cAMP via PKA)
How does arsenic poisoning inhibit glycolysis?
arsenate subs for phosphate in G3P—>1,3-BPG
Where/how much ATP is req’d in glyoclysis?
Two total:
- 1 by the hexokinase rxn
- 1 by F-6-P—>F-1,6-P
What is 2,3-BPG?
made from 1,3-BPG
decr o2 affinity of hemoglobin
What are the isozymes of LDH?
- LDH is tetramer
- h4 in heart: lactate—>pyruvate
- m4 in SKM & liver: pyruvate—>lactate
High plasma [H4-LDH] is indicative of what pathology?
acute M.I. (recall that H4 is heart-specific isozyme)
In the conversion of glucose to lactate by glycolysis, how many of the enzymes involved exist as different “isozymes” in different tissues? 1, 2, 3 or 4?
3—pyruvate kinase, LDH and hexo-/gluco-kinase
Why bother making lactate?
need to oxidize NADH—> to NAD+
