QUIZ 1 (Carbohydrate Metabolism) Flashcards
When ATP needs outpace oxygen delivery, ___ is the primary source of energy.
Glycolysis
General reaction of Glycolysis
1 glucose —> 2 pyruvate + 2 ATP
*does NOT require oxygen = anaerobic reaction
Glycolysis is a critical source of ATP especially in ___ because __.
RBC - they don’t have mitochondria to use aerobic respiration
Glucose is the prefered source of fuel for ___ and ___.
RBC (because they lack mitochondria)
Brain (under non-starvation)
The ___ is the distribution center of glucose.
Liver
De novo synthesis of glucose is termed ___ and occurs in the ___.
Gluconeogenesis
Liver
GLUT Transportors
GLUT1 - brain and RBC = high affinity
GLUT2 - liver and kidneys = low affinity
GLUT3 - neurons = high affinity
GLUT4 - skeletal muscle, fat, heart = low affinity
*regulated by INSULIN!
Km is ____ proportional to ___.
Inversely
Affinity (of substrate binding)
Glucose transportor ___ is sequestered in vesicles, but inserted into the membrane in response to ____ which induces ___.
GLUT4
Insulin binding
Glucose uptake into the cell
Where does each occur?
Glycolysis
Gluconeogenesis
Glycolysis - cytoplasm of all cells
Gluconeogenesis - in liver / kidney / small intestine
___ in the liver and pancreas traps glucose within the cell by___.
Glucokinase / adding Po on glucose
Hexokinase traps it for all other cells
What enzyme is associated with the rate limiting step in glycolysis?
PK1 (Phosphofructokinase-1)
What reactions require ATP in glycolysis?
Trapping of glucose in cell by hexokinase /glucokinase
Conversion of Fructose 6P to Fructose 1,6-BP by Phosphofructokinase-1
*RLS!!
What enzymes are responsible for the generation of ATP in glycolysis?
Phosphoglycerate Kinase
Pyruvate Kinase
Explain how PFK-2 affects glycolysis
Works as a kinase when dephosphorylated (favored by INSULIN)
=promotes PFK-2 activity —> activates PFK-1
Works as a phosphatase when phosphorylated (favored by GLUCAGON)
=inhibits PFK-2 activity —> deactivates PFK-1
*PFK-1 is the RLS in glycolysis
Tarui Disease is due to a deficiency in ___, which causes ___.
PFK-1
Inhibition of ATP production via glycolysis
Pyruvate Kinase (PK) regulation
During fed state = insulin is high
—>activates phosphatase to de-phosphorylate PK = active PK
During starvation = glucagon is high
—> activates kinase to phosphorylate PK = inactive PK
Glycolysis is ___ during exercise to meet energy requirements.
Activated
Defective glycolytic enzymes (causing ineffective glycolysis) especially affects ___ resulting in ___.
RBCs
Hemolytic anemia
During extreme starvation, the brain “switches” from glucose to ___ as a fuel source.
Ketone bodies
Carbohydrate metabolism is orchestrated by ___ and ___ in blood.
Insulin / Glucagon
Fanconi-Bickel Syndrome
Mutation in GLUT2 transporter inhibits uptake of glucose/fructose/galactose in the liver and pancreas
Direct glucose reserves are sufficient to need glucose needs for ___.
About 1 day
*whole body need 160g / brain needs 120 g / glycogen in body stores 190g
Which 4 enzymes of gluconeogenesis bypass glycolysis?
Glucose 6 Phosphatase
—>bypasses Hexokinase/Glucokinase
Fructose 1,6 Biphosphatase
—>bypasses PK-1
PEP Carboxykinase + Pyruvate Carboxylase
—>bypass Pyruvate Kinase
When is glycolysis favored over gluconeogenesis?
High [glucose] / Insulin / [AMP] / [Fru 2,6-BP] / [Fru 1,6-BP]
Low Glucagon / [ATP] / [citrate] / [Glc 6-P] / [Fru 6-P]
Pyruvate Carboxylase is located where?
Mitochondria
What enzyme allows for the conversion and reconversion of OAA to Malate?
Malate Dehydrogenase
What is the rate limiting step of gluconeogenesis?
Conversion of Fructose 1,6 Biphosphate to Fructose 6P
—> by Fructose 1,6- Biphosphatase
___ is the enzyme that is associated with a GLUT transporter (___) and is responsible for converting G6P to glucose.
Glucose 6-Phosphatase
GLUT7
The Cori Cycle connects ___ produces from glycolysis in RBC/muscles to gluconeogenesis in the liver.
Lactate
Precursor of gluconeogenesis:
Carbs / lipids / proteins
Von Gierke Disease (____) is due to a deficiency in ____.
GSD1a
Glucose 6-Phosphatase
*causes inefficient release of free glucose into the bloodstream from the liver after gluconeogenesis and glyconeogenesis
Monosaccharides of:
- sucrose
- galactose
- sucrose = glucose + fructose
- galactose = glucose + lactose
Uptake of fructose, glucose, and galactose is done by…?
SGLT1 —> glucose / galactose / Na+
GLUT5 —> fructose
GLUT2 —> glucose / galactose / fructose
*into the bloodstream
Glucose is converted to ___ by ___ and then converted to fructose by___.
Sorbitol / Aldose Reductase / Sorbitol Dehydrogenase
Fructose can be directly converted to Fructose 6P by ___.
Hexokinase
Fructose can be converted to Fructose 1P by ___ which feeds into glycolysis/gluconeogenesis as Glyceraldehyde 3P.
Fructokinase
Fructose can either enter glycolysis or ___.
become fats (triacyglycerols)
Fructose metabolism is faster than glucose because it ___.
bypasses the RLS of glycolysis
*reason why high fructose corn syrup is NOT healthy; it leads to unregulated generation of Acetyl-CoA which is converted to fatty acids (excess fatty acids lead to obesity and fatty liver)
Galactose can be converted to Galactose 1P by ___.
Galactokinase
What is the rate limiting enzyme in Galactose metabolism?
GALT (glucose 1P uridyltransferase)
If Galactose is not converted to Glucose, what may occur?
It can be converted to Galactitol and accumulate in the eyes, giving rise to cataracts
*usually due to a deficiency in Galactokinase or GALT
Galactosemia is a result in a deficiency of ___ or ___.
Galactokinase / GALT (glucose 1P uridyltransferase)
What is the main products of the Pentose Phosphate Pathway?
NADPH / Ribulose 5P
In the PPP, conversion of G6P to Ribulose 5P is a ___ reaction.
Irreversible oxidative (catabolic)
What enzyme is associated with the RLS of the PPP?
G6P Dehydrogenase
G6P Dehydrogenase deficiency is characterized by…?
Hemolytic anemia
*the need for NADPH is high; NADPH can activate glutathione (antioxidant in RBC) during infections
NADPH regenerates ___ which is an important antioxidant that detoxifies hydrogen peroxide.
Glutathione
Rapidly dividing cells (including cancers) favor the production of ___ from the PPP.
Ribose 5P
*used in DNA/RNA synthesis
Glycogen is formed by ___ and ___ glycosidic bonds.
alpha-1,4 (linear) / alpha-1,6 (branching)
- Glycogen Synthase
- Glucosyl (4:6) Transferase
Glycogen is stored in the form of ___ in ___.
granules / liver and muscles
Function of glycogen:
Liver vs muscle
Liver glycogen = regulates blood glucose
Muscle glycogen = provides glucose/energy for physical activity
What is the rate limiting enzyme of glycogenesis? glycogenolysis?
Glycogen Synthase
*makes alpha-1,4 glycosidic bonds
Glycogen Phosphorylase
Glycogen phosphorylase requires ___ as a cofactor during glycogenolysis.
Pyridoxal Phosphate (Vitamin B6)
___ is the debranching enzyme in glycogenolysis.
Transferase
___ removes glucose in the form of ___ during glycogenolysis.
Glycogen Phosphorylase / Glucose 1P
Once Glucose 1P is converted into Glucose 6P, it will…
Be converted to glucose in the liver (by Glucose 6 Phosphatase)
Be used to make energy in muscles
____ is an enzyme found only in the liver.
Glucose 6 Phosphatase
*reason why muscles cannot reform glucose; gluconeogenesis only occurs in the liver!
Regulation of Glycogen Synthase and Glycogen Phosphorylase:
Glycogen Synthase:
-Po = ACTIVE (high insulin leads to dephosphorylation)
+Po = inactive
Glycogen Phosphorylase
-Po = inactive
+Po = ACTIVE (high glucagon leads to phosphorylation)
Glucagon does not act on ___.
Muscle
Insulin binds to ____ type receptor, while Glucagon binds to a ____ receptor.
GPCR / Tyrosine Kinase
Insulin binds receptor and then…
Glycogen synthesis or degradation?how?
Activates PkB
—> activates phosphatase
—> dephosphorylates Glycogen Synthase (active) and Glycogen Phosphatase (inactive)
—>Glycogenesis
Glucagon binds receptor and then…
Glycogen synthesis or degradation?how?
Activates PkA (a kinase)
—>phosphorylates Glycogen Synthase (inactive) and Glycogen Phosphorylase (active)
—>Glycogenolysis
Insulin causes ___ while Glucagon causes ___.
Dephosphorylation / phosphorylation
Glycogen Storage Disease (1-6) - enzymes involved
0 - Glycogen Synthase
1 - Glucose 6 Phosphatase
2 - Acid Maltase
3 - Alpha-1,6-glucosidease = debrancing enzyme
4- Glucosyl (4:6) transferase = branding enzyme
5 - Glucose Phosphorylase in muscle
6 - Glucose Phosphorylase in liver
