Carbohydrate Metabolism II Flashcards
Overview of Glucose Metabolism: Glycolysis and Gluconeogenesis
Gluconeogenesis occurs mainly in the _____.
Synthesis of glucose from pyruvate utilizes many of the
same enzymes as _____.
Three Glycolysis reactions have such a large negative ΔG
that they are essentially _____:
_____ (or Glucokinase)
_____
_____.
These steps must be _____ in gluconeogenesis.
liver glycolysis irreversible hexokinase phosphofructokinase pyruvate kinase bypassed
1st Bypass Reaction: Formation of Phosphoenolpyruvate (PEP)
• PEP cannot be directly formed from pyruvate:
– Formed through a two-step process via _____.
– OAA is an intermediary of the _____.
oxaloacetate (OAA)
TCA cycle
1st Bypass Reaction: Formation of Phosphoenolpyruvate (PEP)
• Step 1: Pyruvate is carboxylated by a _____ to form OAA:
– Pyruvate carboxylase is a biotin-dependent _____
enzyme.
– Requires the hydrolysis of one molecule of _____.
• Step 2: OAA is decarboxylated to form PEP by a
_____: – Requires the hydrolysis of one molecule of _____.
– PEPCK is located in the _____, in _____, or both. – It is widely distributed in tissues.
PEP - _____ molecule
pyruvate carboxylase
mitochondrial
ATP
phosphoenolpyruvate carboxykinase (PEPCK) GTP cytosol mitochondria high energy
2nd Bypass Reaction: Formation of Fructose 6-phosphate
_____ hydrolyzes Pi from fructose 1,6-bisphosphate to form fructose 6-phosphate
- – not a _____ of the _____ reaction
- – ATP is not produced when the phosphate is removed; Pi is release by _____
Fructose 6-phosphate is converted to glucose 6-phosphate by the same isomerase used in glycolysis (_____)
fructose 1,6-bisphosphatase reversal phosphofructokinase-1 PFK1 hydrolysis phosphoglucoisomerase
3rd Bypass Reaction: Formation of Glucose
• Glucose 6-phosphatase hydrolyzes Pi from glucose 6- phosphate, and free _____ is released into the blood:
– Not a reversal of the _____ reaction.
– _____ is not produced when the phosphate is removed; Pi is released by _____
glucose
glucokinase
ATP
hydrolysis
Glycolysis vs. Gluconeogenesis
Glycolysis accomplishes a negative ΔG while yielding reducing equivalents (2 _____) and 2 net _____.
• Gluconeogenesis requires the use of 4 _____ and 2 _____ to achieve its negative ΔG.
NADH
ATP
ATP
GTP
Gluconeogenesis and Glycolysis: a Futile Cycle?
Glycolysis and Gluconeogenesis both achieve _____, therefore both are _____.
If both pathways were simultaneously active in a cell, it would constitute a _____ that would waste energy.
An apparent “futile cycle” is actually the site of a finely _____ mechanism.
negative deltaG
spontaneous
“futile cycle”
regulated
Reciprocal Regulation of Gluconeogenesis and Glycolysis
- To prevent the waste of a tuile cycle, glycolysis and gluconeogenesis are _____
- reciprocal allosteric regulation by _____:
- -Phosphofructokinase (glycolysis)
- –_____ by ATP and _____ by AMP
- -Fructose-1,6-bisphosphatase (gluconeogenesis):
- –_____ by AMP
- high cellular ATP/AMP:
- -glucose is not _____ to make ATP
- low ATP/AMP:
- -the cell does not expend _____ in the synthesis of glucose
reciprocally regulated adenine nucleotides inhibited stimulated inhibited degraded energy
first mechanism that regulates both enzymes involved in the negative free energy = _____
this is considered to be a _____ regulation
allosteric regulation by adenine nucleotides
“local”
Reciprocal regulation of Gluconeogenesis and Glycolysis
• Systemic regulation in liver cells by the cAMP cascade:
• Makes glucose available for release to the bloodstream:
– Inhibition of _____.
– Stimulation of _____.
Triggered by low _____.
Mediated by _____.
_____ of enzymes and regulatory proteins by Protein Kinase A (cAMP-
–Dependent Protein Kinase): Pyruvate Kinase:
Glycolysis enzyme that is _____ when phosphorylated.
– CREB (cAMP response element-binding protein):
Activates transcription of the _____ gene, leading to increased _____.
– Phosphofructokinase 2 makes and degrades an allosteric regulator, _____.
glycolysis gluconeogenesis blood glucose glucagon phosphorylation inhibited PEP carboxykinase gluconeogenesis fructose-2,6-bisphosphate
Reciprocal regulation of Gluconeogenesis and Glycolysis
Reciprocal regulation by fructose-2,6-bisphosphate (F2,6P):
F2,6P stimulates _____.
F2,6P allosterically _____ the Glycolysis enzyme PFK-1 (see CHO lecture 1, slide 47).
F2,6P activates the transcription of the _____ gene, the liver variant of Hexokinase that phosphorylates Glc to G6P, the input to _____.
F2,6P allosterically inhibits the gluconeogenesis enzyme _____.
glycolysis activates glucokinase glycolysis fructose-1,6-bisphosphatase
Reciprocal regulation of Gluconeogenesis and Glycolysis
Summary of effects of the glucagon-cAMP cascade in the liver:
Gluconeogenesis is _____.
Glycolysis is _____.
Glycogen breakdown is _____.
Glycogen synthesis is _____.
_____ is formed for release to the blood.
stimulated inhibited stimulated inhibited free glucose
Physiological Significance of Gluconeogenesis
• Failure of gluconeogenesis:
– Usually _____.
– Hypoglycemia leads to _____ and coma.
– Glucose is also necessary to maintain TCA cycle intermediates for _____.
• Excessive gluconeogenesis:
– May lead to _____ in critically ill patients.
– Due (in part) to excess of the stress hormone _____.
• Energy cost:
– _____ on very low carbohydrate diets.
– The continual demand for glucose leads to gluconeogenesis from _____.
– ATP required for gluconeogenesis is provided by increased oxidation of _____.
fatal
brain dysfunction
fat metabolism
hyperglycemia
cortisol
weight loss
amino acids
fatty acids
Part II: The Tricarboxylic Acid Cycle (TCA; Krebs Cycle; Citric Acid Cycle)
• _____ of proteins, fats, and carbohydrates.
• Two stages of cellular respiration.
– Stage 1: Oxidation of fuels.
— Stage 1a: oxidation to _____.
— Stage 1b: oxidation of acetyl groups to
_____ with energy release as reduced
electron carriers _____ and _____.
• Stage 2: ATP generation from electrons
carried by NADH and FADH2 to reduce _____ to _____.
catabolism acetyl CoA CO2 NADH FADH2
O2
H2O
Alternative Fates of Pyruvate and Regeneration of NAD+
A. Pyruvate is metabolized in the _____, and the reducing power of NADH is used to synthesize ATP in the _____.
B. Fermentation to lactate in vigorously contracting muscle, in erythrocytes, in some other cells, and in some microorganisms: _____ and _____ form lactate, regenerating _____.
C. In yeast and other microorganisms, pyruvate is converted to _____.
TCA (Krebs) cycle
mitochondria
NADH
pyruvate
NAD+
ethanol
The TCA and oxidative phosphorylation take place in mitochondria
Glycolysis occurs in the _____
Formation of acetyl COA and the TCA cycle > both take place in the _____ (not associated with the membrane; _____ proteins)
cell
matrix of the mitochondria
soluble
TCA cycle: Important points
• Function: to fully \_\_\_\_\_ derived from carbohydrates, fats and proteins to CO2. • Carbon atoms delivered to the TCA cycle in the form of \_\_\_\_\_. • This oxidation produces: \_\_\_\_\_: • GTP • NADH • FADH2 \_\_\_\_\_ used for biosynthetic processes, e.g. fatty acids, amino acids • \_\_\_\_\_
The TCA is an _____ pathway in _____.
The cycle is regulated by the state of cellular energetics and _____.
TCA cycle intermediates must be _____ to continue the cycle for energy production, as well as to provide substrates for biosynthetic pathways.
oxidize carbon atoms acetyl CoA high-energy molecules metabolic intermediates CO2
aerobic energy-producing
mitochondria
O2 availability
maintained
Formation of Acetyl-Coenzyme A from Pyruvate
Pyruvate:
- Transported into _____ by a transporter
- -Decarboxylated to acetyle-CoA by the _____
Pyruvate dehydrogenase:
- multi-enzyme complex containing multiple copies of _____ enzymes
- several coenzymes:
- – _____
- – coenzyme A (pantothenic acid)
- – _____
- – thiamine pyrophosphate (thiamine)
The release of _____ provides a powerful driving force for the reaction.
mitochondria
pyruvate dehydrogenase complex
three
NAD+ (niacin)
lipoamide FAD (riboflavin)
CO2
Coenzyme A has a _____; the vitamin _____ is bonded to the nt; linker region: _____ (in reduced form ends in a thiol group)
in blue is the acetyl part (binds to the _____ group); everything else remains the same (vitamin b5 and the nt.)
nucleotide portion
B5
beta-mercapto ethylamine
thiol
