Carbohydrate Metabolism Flashcards
Anaerobic Carbohydrate Metabolism
- Glucose Transport
- Glycolysis
- Other Monosaccharides
- Pyruvate Dehydrogenase
- Glycogenesis and glycogenolysis
- Gluconeogenesis
- Pentose Phosphate Pathway
Glucose Transport
4 Types:
Glut 1
Glut 2
——– Specific to
1. pancreatic cells: sense high glucose
concentration and respond with insulin
release
2. hepatocytes: Store glucose as it travels
from intestine to the liver through hepatic portal
vein if glucose concentration is >1/2km
Glut 3
Glut 4
——– Specific to
1. adipose tissue: with increased insulin levels,
convert excessive glucose to first, DHAP, and
second to glycerol phosphate, which can store
fatty acids as triacylglycerol
2. muscle tissue: with increased insulin levels, uptake
excessive glucose and convert it to glycogen
****Review 291*********
Glycolysis
An anaerobic energy yielding pathway that converts glucose to 2 pyruvates in addition to producing 2 electron carriers [NADH] and 2 ATPs
Certain cells without oxygen and mitochondria like erythrocytes can produce energy only through glycolysis****
Glycolysis Steps
- Transport of Glucose inside the cell using Glucokinase
- Phosphorylation of glucose to G-6-P by Hexokinase to prevent its transport using GLUT
- G-6-P———Isomerase————-F-6-P
- F-6-P———PFK-2——————–F 2,6 BP
[F 2,6 BP activates PFK1] - F-6-P——–PFK-1———————F 1,6 BP
- F-1,6 BP—-Aldolase—————-Glyceraldehyde 3-P
- Glyceraldehyde 3-P—–Glyceraldehyde-3-P- Dehydrogenase———NAD>NADH &—-1,3 BPGlycerate
- 1,3 BPG——————-Phosphoglycerate Kinase—————————-ADP>ATP—————3-phosphoglycerate
- 3-phosphateglycerate—-mutase–2-phosphoglycerate
- 2-phosphoglycerate–Enolase–phosphoenolpyruvate
- PEP———-Pyruvate Kinase—–ADP>ATP———————————————————-Pyruvate
Fermentation
The process of NAD+ replenishment and lactate production through reduction of pyruvate with NADH oxidation.
**Occurs in absence of oxygen & mitochondria**
pg. 294
High Energy-Yielding Intermediates of Glycolysis
1,3 BPG [Bisphosphoglycerate]
&
PEP [Phosphoenolpyruvate]
Both of them produce ATP anaerobically through substrate-level phosphorylation***
DHAP
AKA [Dihydroxyacetone-phosphate]
Glycolysis intermediate formed from F 1,6 BP by rxn of aldolase that gets isomerized into Glycerol-3-P by glycerol-3-p-dehydrogenase before being converted into glycerol backbone which can be used for triacylglycerol storage by adipose and hepatic cells
Gluconeogenesis
Production of glucose from other biomolecules through liver
**The reverse process o glycolysis**
Irreversible Enzymes of Glycolysis
- Glucokinase/Hexokinase
- PFK-1
- Pyruvate Kinase
These enzymes are replaced by others in gluconeogenesis*******
Glycolysis and Hemoglobin O2 Dissociation Curve in Erythrocytes
Erythrocytes, due to their lack of mitochondria, only employ anaerobic glycolysis as a mean for energy production.
**They use their BPG mutase to convert 1,3 BPG to 2,3 BPG which upon binding to the beta chain of HbA they carry, decreases their affinity for oxygen and forces them to release more oxygen in the tissues.
****O2 Saturation in the lungs remains at 100% unless the concentration of 2,3 BPG increases too much, leading to dramatic rightward shift of HbA O2 dissociation curve, indicating excessive O2 release in the tissues.
*******2,3BPG does not bind well to HbF; therefore fetuses obtain their oxygen from their mother through transplacental transmission.
Types of Hemoglobins
HbA———-Adult Hemoglobin
HbF———-Fetal Hemoglobin
Monosaccharides Metabolised by Cells
- Glucose
- Galactose
- Fructose
Source of Galactose in Diet
Lactose in Milk that divides into 1. Galactose & 2. Glucose by Lactase
Lactase
Brush-border enzyme of duodenum that breaks down lactose into galactose and glucose
Galactose Metabolism
- Galactose, broken down from lactose by lactase, reaches the liver through hepatic portal vein
- Galactokinase phosphorylates it to G-1-P to trap it inside the cell
- G-1-P Uridyltransferase & an epimerase convert G-I-P to glucose-I-phosphate
Epimers
Diastereomers that differ only at one chiral carbon
Epimerases
Enzymes that catalyze conversion of one sugar epimer to another
Diet Source of Fructose
- Fruits,
- Honey
- Sucrose
Fructose Metabolism
- Sucrase divides sucrose into fructose and glucose
- Fructose travels up to the liver from the intestine through the hepatic portal vein
- Fuctokinase phosphorylates fructose to F-I-P
- Aldolase cleaves F-I-P into DHAP & glyceraldehyde
- Proximal renal tubules metabolize the smaller segments
pg. 299
Pyruvate Dehydrogenase Complex
Complex of enzymes that convert pyruvate to acetyl-CoA to start either 1. citric acid cycle if ATP is needed, or 2. Fatty acid synthesis if ATP is sufficiently present
- ***Require multiple cofactors and coenzymes such as
1. lipoic acid
2. NAD
3. FAD
4. CoA
5. Thiamine pyrophosphate
Possible Fates of Pyruvate at the end of Glycolysis
- Conversion into Acetyl-CoA by PDH
- Conversion into lactate by dehydrogenase
- Conversion into oxaloacetate by pyruvate carboxylase
Glycogen
Identity:?
Source of glucose storage in muscles and liver where glucose becomes mobilized either to maintain an optimal level of blood sugar or to enable muscle contraction
Chemical Nature
In the cells, glycogen gets stored in the cytoplasm in granule forms where linear or branched chains of glycogen radiate outward from a central, core protein
Starch
Excessive glucose stored in plant cells
Glycogenesis
Synthesis of glycogen granules that starts with
1. conversion of glucose-6-phosphate to G-I-P
follows with:
2. interaction of G-I-P with UTP to yield Pp and UDP-glucose
& ends with
3. activation of glycogen synthase with insulin & G-6-P to produce the alpha 1,4 glycosidic bonds of the linear glucose chains that will bind to glycogenin
Glycogenin
Core protein in glycogen granules to which glycogen chains attach
Glycogen Synthase
Enzyme in glycogenesis that produces the alpha 1,4 glycosidic bonds found in the linear glucose chains of glycogen granules after it gets activated by insulin and G-6-P
Glucagon and epinephrine inhibit the action of glocogen synthase**
**Rate limiting step of glycogenesis**
Function of Branching Enzymes in Glycogenesis
- Glycogen Synthase synthesizes an alpha 1,4-linked polyglucose chain
- Branching enzyme hydrolyzes an alpha 1,4-bond
- Branching enzyme attaches the oligoglucose unit as a branch with an alpha-1,6-bond
- Glycogen synthase extends the branches
Glycogenolysis
Process of breaking down glycogen with a phosphorylase
- Glycogen Phosphorylase, activated by glucagon in the liver and by AMP & epinephrine in the muscles, breaks down alpha-1,4-links of glucose chains of glycogen granules and releases G-I-P
* ****does not break alpha-1,6-bonds**** - De-branching enzyme hydrolyses the alpha-1,4-bond closest to the branch point
- De-branching enzyme transfers the oligoglucose to the end of another chain
- De-branching enzyme hydrolyzes the alpha-1,6-bond, releasing the single glucose from the former branch
- Mutase converts G-I-P to G-6-P
- G-6-phosphatase converts G-6-P to Glucose
Gluconeogenesis
I. Reversal process of glycolysis that takes place in hepatocytes to produce glucose for other cells when adequate supply of ATP exists in hepatocytes
II. Obtains its energy from beta-oxidation of fatty acids released from triacylglycerols held in hepatic adipose tissues
I. Fatty acids convert to ATP
III. Convenient during lengthy hours of starvation
Uses the following substrates:
- glycerol-3-phosphate [triacylglycerol] from adipose tissues
- Lactate [anaerobic glycolysis]
- Glucogenic amino acid
Amino Acid Subcategories
- Glucogenic Amino Acid
All except leucine and lysine can be
converted to intermediates that can feed into
gluconeogenesis - Ketogenic Amino Acid
Can be converted into ketone bodies that can
be used as a source of energy during
prolonged periods of starvation
Enzymes Converting Intermediates into Glucose through Gluconeogenesis
- Lactate to pyruvate by Lactate dehydrogenase
- Glycerol-3-P to DHAP by glycerol-3-phosphate dehydrogenase
- Alanine to pyruvate by alanine aminotransferase
Enzymes Responsible for Irreversible Steps of Glycolysis
- Glucokinase
- PFK1
- Pyruvate Kinase
Gluconeogenesis’s Enzymes that Catalyze the Irreversible Steps of Glycolysis for Glucose Synthesis
- Pyruvate Carboxylase
I. Converts pyruvate to OAA in the
Mitochondria
II. OAA gets reduced to Malate that can
leave the mitochondria via malate-
aspartate shuttle
III. In the cytoplasm, malate gets oxidized to
OAA - PEPCK [Phosphoenolpyruvate Carboxykinase]
I. converts OAA to PEP in the cytoplasm
using GTP
II. Circumvents the irreversible catalysis of
pyruvate kinase - Fructose-1,6-Bisphosphatase
I. Circumvents PFK1
II. Converts F-1,6-BP to F-6-P in the cytoplasm
III. Activated by ATP
IV. Inhibited by AMP & F-2,6-bisphosphate
V. Rate-limiting step of gluconeogenesis - Glucose-6-Phosphatase
I. Circumvents Glucokinase & Hexokinase
II. Convert G-6-P to Glucose in the Lumen of
endoplasmic reticulum [ER]
Free glucose then travels back to the cytoplasm to be transported by GLUT**
**3.IV. In glycolysis, F-2,6-BP activates PFK1; therefore it logically inhibits F-1,6-Bphosphatase**
Phosphatase
Enzyme that dephosphorylates
Opposes the action of kinases
Pentose Phosphate Pathway
— AKA Hexose Monophosphate Shunt [HMP]
—Location —-Takes place in cytoplasm of cells
—Purpose
I. Produces NADPH
II. Produces ribose 5-phosphate
**necessary for nucleotide synthesis
—Important rate-limiting Enzyme
I. G6PD [Glucose-6-phosphate dehydrogenase]`
PPP Steps
pg. 312
Difference B/w NAD+/NADH & NADP+/NADPH
-NAD+ is a potent oxidizing agent and electron acceptor that once reduced to NADH can produce ATP after being fed into the electron transport chain
–NADPH is a reducing agent and electron donor that contributes to
I. biosynthesis of fatty acids and cholesterol
II. protection against free radical oxidative
damage by maintaining supply of reduced
glutathione
[serves as an antioxidant]
III. bacterial activity by producing bleach in certain
white blood cells
Glutathione
reducing agent that reduces free radical formation to prevent damage to cell DNA and cell membrane
pg. 313
