GLYCOLYSIS

Draw out the glycolysis cycle, with enzymes and regulators

see slide

What are some cells that are restricted to anaerobic degradation of glucose? Why is this the case? What type of phosphorylation happen here?

RBC bc no mitochondria

Skin (for lactic acid defense)

excercising muscle

intestinal mucosa

cancer cells (although can do angiogenesis)

substrate-level phosphorylation

What are the three steps that are regulated in glycolysis. How are they regulated.

hexokinase: regulated negatively by its product G6P

PFK-1: + by fructose 2,6 BP and AMP; - by ATP and citrate

Pyruvate Kinase: + by fructose 1,6 BP; - ATP

Explain how hormones indirectly regulate PFK-1. Make sure to include the mechanism.

High insulin/glucagon ration = lower PKA bc lower cAMP; this causes dephosphorylation of PFK-2; this causes the creation of fructose 2,6 biphosphate; this is an activator of PFK1;

vice versa for opposite

Describe the function of
Glut-1

Glut-2

Glut-3

Glut-4

What is special about glut 4?

What is the consequences of GLUT-1 deficiency syndrome

Glut1: RBC and blood brain barrier

Glut2: pancreas, liver, kidney

Glut 3: neuron

Glut 4: skeletal muscle and adipocyte (ONLY INSULIN DEPENDENT RECEPTOR)

Glut-1 deficiency = affects nervous system = intractable seizures in infancy and developmental delay

What is Glut 5?

for fructose for small intestine and testes

Compare and Contrast Hexokinase and Glucokinase.

What does Liver Glucokinase do? What does Pancreatic glucokinase do?

Hexo: low km, low Vmax, in most tissues, active during fasting state, inhibited by product

Gluco: high km, high vmax, in liver/pancreas, active during feeding state, inhibited by product (F6P), activated by substrate (glucose)

Liver glucokinase: helps prevent hyperglycemia during fed state

pancreatic glucokinase: acts as glucose sensor that releases insulin when high glucose.

what happens to pyruvate in anaerobic conditions?

become lactate at cost of NADH (product = lactate and NAD+)

What other pathways can glycolysis lead to?

G6P —> pentose phosphate pathway

glyceride + fatty acid = triglyceride

1,3 biphosphateglycerade + 3 phosphateglyceride = 2,3 biphosphateglycerate (regulation of O2 release)

3 phospho glycerate = serine

pyruvate = alanine

What is the fate of pyruvate

become lactate

become acetyl CoA (go into TCA or fatty acid synthesis)

become alanin via transanimation

can become oxaloacetate (TCA cycle or GNG)

How does insulin/glugagon regulate glycolysis?

Insulin positively regulate all of the irreversible enzyme; glugagon does opposite

In glycolysis, which reaction doess arsenic poisening inhibit?

inhibit G3P —> 1,3 biphosphateglycerate

What is fructokinase deficiency (essential fructosuria) and what are the consequences

when fructose is ingested, fructokinase needs to phosphorylate it; defeciency =

1. fructosemia (in blood) and fructosuria (in urine);

consequence = benign; no symptoms

What is the consequencces of Aldolase B deficiency?

aldolase B cleaves fructose-1-phosphate into GAP and DHAP

if not cleaved:

1. accumulation of F1P (toxic to all cells) —> inhibition of fructokinase

accumulation = ATP overuse and accumulation of AMP; degradation of AMP —> uric acid formation

depletion of Pi due to not being able to use F1P for energy via glycolysis or GNG = low ATP synthesis via ATP; Liver low energy —> liver malfunction —> liver damage

2. it also cleaves Fructose 1,6 Biphosphate —> GAP and DHAP

Consequences:

accumulation of F1,6BP

no GAP, no DHAP, no ATP synthesis via glycolysis

depletion of Pi trapped in F1,6BP —> low atp synthesis for liver function —> accumulation of Bilirubin —> jaundice

3. adolase b = reversible, thus can participate in GNG

   1. no GNG = hypoglycemia

   2. accumulation of pyruvate = lactic acid

What does deficiency in adolase A result in?

nonspherocytic hemolytic anemia with episodes of rhabdomyolysis followed by febrile illness (kidney damage)

What does deficiency of triose phospahte isomerase (TPI) result in?

neonatal-onset hemolytic anemia, progessive hypotonia leading to evential diaphragm paralysis and cardiomyopathy

What does flouride do in glycolysis

inhibits enolase resulting in a decrease in ATP synthesis; blood samples of glucose quantification are collected in tubes containing fluoride

What diseases can we use by observing fluctuation in LDH isoenzymes?

Cardiac (myocardial/pulmonary infarctions)

hepatic (hepatitis and cirrhosis)

skeletal muscle (hypoxia and muscle trauma)

neoplastic isorders: leukemias and large tumors

what is MODY?

maturity-onset diabetes of the young type 2 is caused by a mutation in the pancreatic glucokinase gene leading to nonprogressive hyperglycemia which can be managed by diet alone.

What are some consequence of Phosphofructokinase-1 deficiency?

causes inefficient use of glucose stores by RBCs and muscle leading to hemolytic anemia and muscle cramping

What is a key enzyme in recovery uring ischemia and why?

G3PDH because it allows the synthesis of lactate and the recycling of NAD+

what can deficiency in pyruvate kinase cause?

(autosomal recessive) leads to decreased ATP production causing disturbance in cell membrane gradient and loss of ions and water causing RBCs to contract, crenulate, and die due to nonspherocytic hemolytic anemia.