glycolysis mqster set

Where is glycolysis located

IN the cytosol

What are the inhibitors of PFK 1? How do they make logistical sense?

ATP and citrate since there’s are down stream products which tell PFK 1 that we are in a high energy state already.

What is PK activated by and why

It is inhibited by ATP and citrate,

Activated by AMP and F26BP

What is private kinase activated and inhibited above

They are inhibited by upstream F16BP

Inhibited ATP

Where is ATP used and produced in glycolysis

ATP is being used by PFK1 and ATP is produced by private kinase

Ie net of 2 ATP from 4 made- 2 used.

When insulin is high what is activated?

Activated both PFK1 and pruvate kinase

**** insulin to glucagon levels regulate key enzymes ie glucokinase, PFK1 and pyruvate kinase

When glucagon is high what happens

Inh what insulin activates, ie oppsoite effect

How is PFK1 regulated int he liver?

PFK2 produces F26BP which activates PFK1.

• High insulin + increased F26BP than more active PFK1.

• PFK2 adds phosphate to F6P to activate it to ???

How is glucose transported into the cell

What are the syntoms of GLUT 1 deficiency

Inherited disorder, intractable seizures, dev delay, no medication can fix this.

What is the only insulin depend transporter

GLUT4 - where? Obviously the muscle and adipose tissue.

What is the transporter which transports fructose and where is itfound

GLUT5- small intestine and testes

Is hexokinase or glucokinase specific?

hexokinase is non specific and glucokinase only works on glucose.

What does arsenic affect

The binding of phosphate to Glyceraldehyde 3 phosphate

ldolase deficency

Frites intolerance or aldolase deficency vs fructose kinase deficiency or essential frutosuria

Where is ladolase b vs a located

Ladolase B is in the LIVER.

A patient is found with no mitochondria, what will they have to resort to in terms of energy?

They will have to use glycolysis as their primary source of anaerobic repsitoation as even though they may have oxygen they will not have the mitochondria to go through the TCA cycle.

What kind of phosphorilization does glycolysis go through compared to the TCA?

They go through substrate level phsoprylization compared to oxidiaitive phosphorilization.

How is ATP made form glycolysis and how is this different than the ETC

ATP in glycolysis is made form the substrate level phosphorilization of ATP, this is contrary to ETC where they use oxidative phosphilization

What molecule from glycolysis is used in triglyceride synthesis

Glycerol 3 phosphate

What intermediate form the TCA is directly used in the urea cycle

Aspartate

What molecule connects glycolysis to the TCA

Pyruvate

What is the major energy source for the urea cycle

ATP

What molecule is a precursor for triglyceride synthesis

Glycerol 3 phosphate

What molecule from glycolysis is used from the urea cycle via transanimation

Alanine

Role of acetyl CoA for triglyceride synthesis

Provides fatty acid chains

What pathway provides the energy for lipogenesis

ETC, remember when we make fats we have plenty of energy. If we were breaking down fats then we would use energy from glycolysis.

How does the ratio of insulin/glucagon regulate the synthesis of glucokinase, PFK-1, and pyruvyte kinase?

As the ratio of insulin/glucagon rises, then we will activate the pathways for storage of glucose.

Ie. All enezymes above will be activated.

As the ratio of insulin/glucagon falls then glycolysis will be inh so we can make glycolysis

Ie. All above enezymes will be inhibited

What is the affect of G-6-P to hexokinase?

Inhibited ie too much tells use we can shut off this pathway.

What is the effect of ATP, citrate and NADH to PFK1, and pyruvate kinase?

What steps is ATP used and made? What is the net form glycolysis for 2 units of pyruvate?

PFK1 makes

Bam, a patient has deficency of fructose 2,6 bisphosphate. How will this affect PFK 1 and what does this tell about PFK2?

A defifriceny in F26BP indiicates a possible issue with PFK2 as PFK2 makes F6BP. Thus PFK1 will not be able to be activates and glycolysis will be affected.

Hormones indirectly regulates PFK1 via synthesis of F26BP

High insulin/glucagon —>increased F26BP —→ increased PFK1 act

Low insulin/glucagon —> decreased F26BP —>decreased PFK1 act

What is GLUT-1 deficiency syndrome? What are the symptoms associated witht his disease?

GUT-1 is found in the RBC and blood brain barrier. Will result in decreased glucose int he CSF —→intractable seizures and dev delay.

WHere is GLUT 1 found

RBCs and blood brain barrier

Where is GLUT 2 found and what is special about this transporter.

Bidirectional transported in lever, kidneys, and pancreas

Where is GLUT 3 found?

Neurons

Where is GLUT4 found and what is so special about this transporter

Inmuscles and adipose tissues, ONLY insulin dependent transporter.

Describe the hormone regulation of PK1 in the liver?

Hormones can indirectly regulate PFK1 via F26BP.

WHEN there is high insulin/glucagon we will activate PFK1

When there is low insulin/glucagon then we will inh PFK1.

A patient comes in GLT1 defificeny, what will we see and what are the labs?

We will see this patient most likely have neuron cell death and seisures. When we test the labs we will see that glucose is low in the CSF

Biochem reasoning: IF GLUT1 is def, the RBC and blood brain barrier will be deplete in glucose.,

What is glut 2 responsible for ?

Bidirectional transport in the liver, kidneys, and pancreas

When neurons are low in gluose what GLUT transport protein is not functioning?

The GLUT 3 transporter

What is so special about the GLUT 4 transpotrer

Only insulin depend transporter,, think muscles and acidoses tissue

Where is the lonely GLUT 5 found

Small intestine and testies

What it’s the realtion fo Kmart Vmax in respect to glucokinase and hexokinase

If Km is small such as int he case with hexokinase then the Vmax will also be low.

Clinical relevance: Liver glucokinase is responsible for initial gloves metabolism in the fed state to prevent hyperglycemia

Pancreatic glucokinase as a gloves receptor, increasing insulin in the fed state.

Why is NADH so important in lactic acid fermentation?

NADH is used int he synthesis of lactate from pyruvate, thus it will resupply glycolysis with NAD+ it needs.

***Very important in lack of oxygen environment

Why is glycolysis so important in relation to other cycles?

G-6-P will send 5 carbon sugars to the Penrose phosphate pathway or non directly to glycerol P combined with FA to make triglycerides

2-3 bsiphophoglycerate from 3 phosphoglycerate or 1-3 bis phosphoglycerate will regulate oxygen realse

Where can Acetly Coa go after its synthesis?

It will go to the TCA or be used for FA synthesis and eventual triglyceride storage.

A patient comes in with arsenic poisoning, what enzymes are being affected in glycolysis?

Glyceraldehyde 3 phosphate dehydrogenase

Where are the 3 or reservable enzymes in glycolysis?

Hexokinase/glucokinase

PFK1

Pyruvate kinase

What two enzymes ar affect

What are the two enzymes which ATP are made and what kind of phosphorilization do these take part in?

Substrate level phosorylization will be affected.

Phosphoglycerate kinase and pyruvate kinase will be affected

Describe to patient B why they have frutose intolerance

Yummy yummy fruits —> needs to be pho in t he liver via frutosekinase before cleavage via aldolase

Clinical relevance: blood —> fructosemia

Urine —> frutocetouria(most used blood test****)

No frutokinase = essential frutotouria (benign , no Sxs)

Explain to patient A why they have aldolase B deficiency

In a healthy person: F1P cleaved by aldolase B —> D Glyceraldehyde and DHAP —> GAP

Clinical relevance : we will see a person become deleterious

Reasoning:

• Too much F1P —> ATPn overuse and accum of cAMP —→ Uris acid

• depletionof Pi —> low ATP synthesis (low liver E—>liver malfunction)

Diagnosis: aldolase B def leads to hereditary frutose intolerance

If aldolase B does not cleave F16BP what will happen

Accumulation of F16BP, No gap or DHAP —>no ATP, loss of Pi (accumulation of bilirubin —>jaundice)

Clinical devil ace: build of unconjugated bilirubin caused build up in liver causing yellowing

How can aldolase b deficiency cause hypoglycemia?

Accumulation of pyruvate downstream of gluconeogenesis leads to lactic acid

Clinical relivance: When glucose is low, we make it by condensing GAP and DHAP to F16BP —>hypoglycemia

What are the clinical signs of aldolase b deficiency and how does this differ from fructose intolerance

Aldolase B defificenyc leads to hypoglycemia, uricemia, lactic acidemia

Leads to jaundice, vomiting, and hypoglycemia

Autosomal reccesive

Go over the diagrams in lecture and be able to draw out related concept maps