Glucose metabolism Flashcards
What happens in the mouth when food is ingested?
Mechanical digestion ( chewing and swallowing) Chemical digestion of carbohydrates and fats
What are the enzymes that are functioning in the mouth
Salivary Amylases
Lingual Lipases
What molecules are not digested in the mouth
Proteins
What is the benefit of chewing for the food digestion?
Breaking in smaller pieces
Bigger surface area for enzyme activity
What happens in the stomach with food ingested?
Mechanical digestion ( peristalsis mixing and propulsion)
- Chemical digestion of proteins, fats
- Absorption of lipid soluble substances such as alcohol and aspirin
What enzymes function in the stomach
Gastrin
Gastric lipase
HCl
Pepsin
Where the enzymes in the stomach secreted
Gastric lipase and Pepsin (Chief cells)
HCl( Periatal cells)
Where do lipids digest in the mouth
Lingual lipases are secreted in teeth
What does pepsin do
Starts the digestion of proteins
where is the most absorption in the small intestine
Duodenum
What is done to the food in the small intestine
Mechanical digestion includes mixing and propulsion, primarily by segmentation
Chemical digestion of all molecules
Absorption of peptides, AA,glucose,fats,water,minerals, and vitamins
What enzymes are secreted to duodenum and from what place
From the pancreas Trypsinogen Chymotrypsinogen Carboxypeptidase A and B Active enzymes target specific AA in proteins Pancreatic amylase/lipase
What is happening in the large intestine?
Propulsion and mixing
No chemical digestion( except bacteria)
Absorption of ions, water, minerals, and organic molecules
What is fisculated cow?
A cow that has a whole in the stomach, for the research
Why glucose is an excellent fuel?
- Yields good amount of energy
- can be efficiently stores
- Many tissues can meet energy needs on glucose only
Glucose is a versatile precursor for
- All AA
- membrane lipids
- nucleotides in DNA and RNA
- Cofactors in metabolism
What is glycolysis
Glucose is degraded to puryvate
What is glucoenogenesis
Glucose is formed from non-carbohydrate source
What is glucogenesis
Glycogen is polymerized from glucose units
What is glycogenolysis
Glycogen is degraded to glucose units
What is the first step of glycolysis
Glucose->glucose 6-phosphate
Phosphate group is added OH, instead of H on carbon 6
What enzyme does the first step of glycolysis and what does it use
Hexokinase
With the use of ATP, the hydrolysis of ATP is helped by Mg
Why conversion of glucose to glucose 6-phosphate is important
It traps glucose inside the cell, thus lowering intracellular glucose to allow further uptake
What kind of reaction is the reaction of hexokinase reversible/irreversible?
Irreversible
What is the second step in glycolysis
Glucose- 6 -phosphate is converted to fructose 6 -phosphate
Isomerization reaction to make the first carbon free
What enzyme is used in the conversion of glucose 6-phosphate to fructose 6-phosphate
Phosphohexose isomerase with the help of Mg
What is the role of the reaction with phosphohexose isomerase
Makes the next step easier(C1 of fructose os easier to phosphorylate by PFK)
Allow for symmetrical cleavage by aldose
Is reaction with phosphohexose isomerase reversible/irreversible?
Reversible
What is the third step of glycolysis
Fructose 6-phosphate is converted to fructose 1,6-biphosphate by addition of PO3 to the first carbon
What is the other name for the third step of glycolysis and why
2nd priming phosphorylation, because ATP is used to give phosphate group. This hydrolyses is helped by Mg
What is the enzyme of the conversion of Fructose 6-phosphate to fructose 1,6-biphosphate?
PFK-1 or phosphofructokinase-1
What is the purpose of conversion of fructose 6-phosphate to phosphate to fructose 1,6-biphosphate
Generation of a symmetrical 6-carbon molecule
The reaction with PFK is reversible/irreversible
Irreversible
What is the final reaction of investment stage
Fructose 1,6 -biphosphate is lysed to dihydroxyacetone phosphate(DHAP) and glyceraldehyde 3-phosphate (G3P). ^ carbon sugar to 2 3 carbon sugars
What enzyme breaks Fructose 1,6 -biphosphate
aldolase
What is the role of breaking Fructose 1,6 -biphosphate
Generating high energy phosphate sugars
What is triose phosphate interconversion
Conversion between DHAP and G3P by triose phosphate isomerase
Is aldose and triose phospahte isomerase reversible/irrevesible
Reversible
Why there is triose phosphate interconversion
Because only GAP (glyceraldehyde-3-phosphate) is used in pay-off phase
What is the first reaction of pay off phase
GAP is converted to 1,3-biphosphoglycerate with the addition of inorganic phosphate group to aldehyde end
What is the enzyme that converts GAP to 1,3-biphosphoglycerate
Glyceraldehyde 3-phospahte dehydrogenase (GAPDH)
What is used to perform the first reaction of pay-off phase
Inorganic phosphate
Nad+->NADH+H+
Is the reaction with GAPDH reversible/irreversible
reversible
Why GAPDH can be used as measurement control when giving a treatment for example
Because it is very important and produced a lot by our cells and its concentration do not vary
What is the step of the first ATP production
1,3-biphosphoglycerate gives off the phosphate group in the aldehyde end to ADP to produce ATP and 3-phosphoglycerate
What is the enzyme that helps the transfer of phosphate group to first ADP of glycolysis
Phosphoglycerate kinase with the help of Magnesium
Atp in glycolysis is produced by
Substrate level phosphorylation
Is phosphoglycerate kinase reversible/irreversible
Reversible
What is the migration of the phosphate
the step in pay off phase , when 3-phosphoglycerate is converted to 2-phosphoglycerate
What enzyme catalyses the conversion of 3-phosphoglycerate to 2-phosphoglycerate
Phosphoglycerate mutase with the help of Mg
Explain the mechanism of phosphoglycerate mutase
the enzyme has histidine in its AA sequence. When histidine is phosphorylated , then the enzyme becomes active. The mutase gives off its phosphate to the second carbon of glycerate and at the same time takes the phosphate group from the third carbon
Is the mutase reversible/irrevesible?
Reversible
What is step after 3-phosphoglycerate is converted to 2-phosphoglycerate
2-phosphoglycerate (2-PG) is converted to phosphoenolpyruvate (PEP) by dehydrating 2-PG. OH from the third carbon and H from the second carbon is taken away and the double bond between carbon 2 and 3 is created
What is the enzyme of conversion 2-PG to PEP
Enolase
What is the role of enolase
Generation of a high-energy phosphate compound
Is the reaction with enolase reversible/ irreversible
Reversible
What is the second step when ATP is produced
PEP is converted to pyruvate, giving off phosphate group from carbon 2 to ADP
What is the enzyme for conversion of PEP to pyruvate
Pyruvate kinase with the help of Mg and K
what does the last step of glycolysis includes
Tautomerization -when molecules with the same molecular formula but different connectivity - constitutional isomers, in other words, can easily interchange
The reaction of pyruvate production is reversible/irreversible
Irreversible
Fate of pyruvate
1) Hypoxic or anaerobic conditions (2 ethanol+2 CO2)- fermentation to ethanol in yeast
2) In aerobic conditions pyruvate->acetyl-CoA->TCA->CO2 and H2O
3) Hypoxic or anaerobic conditions to 2 lactate
What enzyme converts pyruvate to lactate. Reversible/irreversible?
Lactate dehydrogenase- reversible
What happens when lactate is produced in muscles
Lactate goes to the liver, where it is converted back to pyruvate and glucose through gluconeogenetic pathway
What is the name of the process when pyruvate is converted to lactate in tissues and then in the liver lactate is converted back to pyruvate
Cori cycle
Erythtocytes convert ___ to ___
Puruvate to lactate
Various carbohydrates can be broken down to ___
Various carbohydrates intermediates of glycolytic pathway
Regulation of anaerobic glycolysis in hypoxic conditions is performed by
Hypoxia Inducible Factor (HIF) which is activated in hypoxic conditions
Explain the regulation of HIF
There is an enzyme prolyl hydroxylase (PHD-2), this is the protein that senses oxygen tension.
In normoxic conditions, it PHD-2 induces HIF ubiquitination and thus degradation
When muscles work vigorously-> hypoxia, PHD-2 does not function, HIF-1 alpha is not degraded, but stabilized. HIF-betacomes and become a functional dimer with alpha.
Once they dimerize, they enter the nucleus and bind to HRE
what isomer of HIF is regulated and ubiquinated
Alpha
What another TF come with HIF alpha and beta
p300/CBP (cAMP response element Binding Protein)
CBP is regulated by
GPCR signaling
HIF target genes
GLUT 1/3 Hexokinase PFK Aldolase GAPDH Phosphoglycerate Kinase Phosphoglycerate Mutase Enolase Lactate dehydrogenase
What tissues mainly depend on glucose
Brain RBC testes renal medulla embryo
How we can get glucose from inorganic sources
Lactate->pyruvate->PEP->glucose
GLucogenic AA->TCA->PEP->glucose
FA->glycerol->GAP->Glucose
CO2 fixation->3-phosphoglycerate->glucose
Recovery after vigorous exercise involves
gluconeogensis
where does gluconeogenesis occur ( tissues)
mainly liver (80%)
Intestinal epithelium
Renal cortex
Which three enzymes can drive glycolysis only forward?
Hexokinase
Phosphofructokinase-1
Pyruvate kinase
What is the last enzyme of glucoenogenesis
Glucose 6-phosphatase. It removes phosphate group from glucose
What enzyme does the reverse reaction of phosphofructokinase-1
Fructose 1,6-biphosphotase-1
Which step requires 2 enzymes in glcucoenogenesis
from pyruvate to phosphoenolpyruvate
It requires two enzymes: pyruvate carboxylase to transform pyruvate to oxaloacetate and PEP carboxykinase from oxaloacetate to phosphoenolpyruvate
What is needed to convert pyruvate to glucose
4 enzymes from glucoenogenesis + 7 reversible enzymes of glycolysis + 6 ATP+ 2 NADHs
Pyruvate To be converted to oxaloacetate needs to
Come inside mitochondria
Pyruvate combines with bicarbonate with the help of pyruvate carboxylase->oxaloacetate
Where oxaloacetate can be converted to phosphoenolpyruvate
In cytosol or in mitochondria
What is used to convert oxaloacetate to phosphoenolpyruvate
GTP, but not ATP
PEP carboxykinase
What is the alternative fate of G6P
Pentose phosphate pathway ( hexose monophosphate pathway)
hexose monophosphate pathway is more common in ( what type of cells)
Highly proliferative cells ( cancer cells, small intestinal cells)
- Cells with FA biosynthesis
- Cells that synthesis sterols ( cholesterol and steroids)
- Cells with oxidative stress
Why leucine and lysine do not contribute to intermediates of glucose synthesis
They are converted to acetyl-CoA, which is immediately converted to a ketone.
Two phases of pentose phosphate pathway
Non-oxidative phase and oxidative phase
What enzyme start pentose phosphate pathway and how
G6P is converted to 6-phosphogluconate with the help of G6P dehydrogenase that uses NADP+ to NADPH
What does phospho-pentose isomerase do
Converts Ribulose 5-phosphate to ribose 5-phosphate
Why phospho-pentose isomerase is important
Because ribose 5-phosphate is the precursor for multiple things (Nucelotides,coenzymes, DNA, RNA)
Another reason why phospho pentose isomerase and G6P dehydrogenase are important
They produce important reducing power NADPH
What enzymes and where are dependent on NADPH
FA synthesis in liver, kidney and lactating mammary gland
Cholesterol/steroid synthesis in liver,adrenal and gonads
Glutathionine reductase uses NADPH in tissues exposed to high O2 (cornea and RBC) and thus oxidative damage
What is the pathway of oxidative damage
O2->( mitochonsrial respirationmsulfa drugs,etc.)->Superoxide radical->hydrogen peroxide->Hydroxyl free radical
Hydroxyl free radical makes damage to lipids, proteins and DNA
What is the prevention of oxidative stress
Hydrogen peroxide is converted to water with the enzyme glutathione peroxidase. This enzymes requires 2 hydrogens from glutathion (GSH)
How GSH is regenerated
NADPH from pentose phosphate pathway donates hydrogens to GSSG (oxidized form) with the help of glutathione reductase
Describe non-oxidative phase of pentose phosphate pathway
Ribose 5-phosphate to Glcuose 6 phosphate in a big picture
ribose 5-phosphate is converted to xylulose 5-phosphate. Transketolase and transaldolases just convert one molecule to another without the addition of carbons or deletion, ultimetely leading to fructose 6-phosphate or Glyceraldehyde 3-phosphate
What reactions are reversible in non-oxidative phase
Practically all of them, except for fructose 1,6 biphosphatese
Where transketolases and transaldolases are over expressed
In cancer cells
How pentose phosphate pathway is regulated
NADPH which is generated can inhibit the reaction that generate NADPH
If the cell needs ATP, G6P will go through glycolysis
If the cell is exposed to oxidative stress or if cell needs a lot of nucleotide synthesize, it will undergo pentose phosphate pathway
