Exam 2: Metabolic Energy Pathways

what is functional metabolic rate?

one way how we can measure activity- a metabolic rate associated with a specific brain function or pathway. Generally, blood flow and glucose consumption increase with activity more than oxygen consumption.

what is resting activity?

one way how we can measure activity- activity of brain cells during conditions in which no specific stimulus is given to the subject- hard to define.

what is brain activation?

one way how we can measure activity- response to a specific stimuli that will result in brain metabolism

what in your neurons is responsible for turning glucose into ATP?

Glucose utilization (glycolytic metabolism)- glucose is metabolized via glycolytic pathway, generating 2 pyruvate and 2 ATP (no oyxgen used), occurs in neuronal cytoplasm

what in your neurons is responsible for turning oxygen into ATP?

Oxygen utilization (tricarboxylic acid cycle, TCA)- pyruvate from the glycolitic cycle and oxygen utilized to generate ATP, occurs in mitochondria

What is the basic structure of a mitcohondria?

Inner and outer membrane, which mitochondrial DNA located in a nucleoid structure.

What does the mitochondrial DNA (mDNA) code for?

Only codes for 13 proteins, 22 tRNA and 2 rRNA

Where does mTDNA come from?

It comes exclusively from the maternal lineage.

Why does mitochondria have its own DNA?

Endosymbiosis- theory that mitochondria were bacteria that became incorporated into early cells and remained there

How do oxygen and glucose get into the brain?

Oxygen freely diffuses through the BBB and cell membrane, glucose is transported past the BBB to cells via transporters (GLUT)

Where is glucose transported to and how does it flow?

Glucose flows down concentration gradient out of arterial flow (brain glu levels change with plasma glu levels), glu is transported to both astrocytes and neurons (astrocytes play major role in metabolizing glucose during brain activation)

What do astrocytes do?

1. Extend their processes around the capillaries and at every synapse in the brain, 2. maintain BBB integrity and have access to oxygen/glucose, 3. synaptic contact help with regulating signaling, and they will express NT receptors, transporters and ion channels

How many synapses does a single astrocyte have contact with?

Around 2 million synapses

What do astrocytes break down?

they have as many mitochondria as neurons, they will break down glucose into lactate to feed TCA cycle (neurons use pyruvate).

How is lactate made by the astrocytes?

made by breaking down stored forms of glucose, which is why astrocytes primarily use it.

What is glycolysis and how does it occur?

It is an anaerobic process (no oxygen) and occurs in cytoplasm of cells.

What is the purpose of glycolysis?

to generate ATP and pyruvate (in neurons) from glucose to be used in TCA cycle. Astrocytes will use glycolysis to. make lactate to be shuttles to neurons for use in TCA cycle.

What is the outcome of glycolysis?

every glucose molecules need 2 ATP to go through the process and in turn makes 4 ATP. Net product is 2 ATP, 2 pyruvate and 2 NADH, w the pyruvate used in the oxidative pathway.

What is the main purpose of the Krebs cycle (TCA cycle)?

to take the pyruvate made from glycolysis and turn it into energy. Also plays a role in amino acid biosynthesis.

Is the TCA cycle (krebs cycle) aerobic or anaerobic?

It is aerobic and utilizes oxygen.

Where does the the TCA cycle occur?

It occurs in the mitochondria.

What is the first step of the TCA cycle?

Convert pyruvate into acetyl CoA.

What is the electron transport chain and where does it occur?

It occurs in the mitochondria and is the process that produces ATP.

What is the net product of the TCA cycle, glycolysis and MAS cycle?

1 glucose produces 32 ATP and uses 6 O2.

Besides ATP generation, what else does the TCA cycle make?

It produces the neurotransmitters glutamate and acetylcholine

What are the other sources of energy besides glucose that neurons can use?

Ketones- through fatty acid breakdown(ketosis), Lactate-through astrocyte metabolism, Glutamate- continually by astrocytes to regulate glutamate signaling and produce ATP, glycogen-to produce limited atp in times of stress.

What are the causes of metabolic disorders?

Fuel delivery disruptions (ischemia, hypoxia), inadequate nutrition, mitochondrial defects and glycogen metabolism

What is diabetes?

a metabolic disorder that results from not enough insulin

What is type 1 diabetes?

The loss of insulin producing cells in pancreas

What is type 2 diabetes?

it is reduces insulin sensitivity of cells

What does insulin do?

Insulin regulates glucose reuptake, so when we eat, insulin is released and it promotes glucose utilization by tissue and conversion to glycogen for later use.

Why is insulin important?

Without insulin or with cells that are resistant to insulin, you end up with high blood glucose levels and not enough glucose getting to your cells. This affects protein synthesis and metabolism.

What is hypoglycemia in diabetes?

Low blood glucose levels, comes from taking too much insulin or not eating enough food

How does hypoglycemia affect a person?

The glucose gradient will disappear, none will get into the brain, and hexokinase will not be working at full capacity. Pyruvate production will fall and TCA cycle wont function well, meaning overall lower production of ATP.

what are CNS symptoms of hypoglycemia?

Abnormal thinking, feeling numb, fatigue, blurred vision, headache, coma, seizures

Treatment for hypoglycemia

eating something that will cause sharp increase in blood glucose levels.

What is hypoxia?

low level of inspired oxygen in the air

What causes hypoxia?

increases altitude, as the decrease in atmospheric pressure reduces pressure for gas exchange in lungs, meaning lungs will struggle to pull in oxygen and pass it to the blood.

Why is the brain more sensitive to oxygen decrease rather than glucose?

Glycogen exists to make up for low glucose, but there is nothing to make up for lack of oxygen

What happens during hypoxia?

Acute hypoxia- NT synthesis decrease, HIF-1 senses oxygen levels and increases glucose transporters and glycolytic enzymes as an effort to increase anaerobic ATP production.

What can cause hypoxia?

High mountain climbing, which can cause altitude sickness ( disorientation, hallucination, impaired judgement, fatigue)

Why does most high altitude climbers experience brain damage?

Decrease in oxygen makes the body produce more red blood cells to compensate for less ATP cycles, which thickens the blood and makes it harder to pump through the heart. This increased blood pressure causes capillaries to create edemas and blood clots-produces strokes.

How do sherpas not experience mountain sickness?

They have better muscle energy metabolism, because of specific genes in their bodies. They have higher anaerobic lactate production (48%) meaning they are able to deal better with metabolic stress.

How do we treat hypoxia?

Remove the person from high altitude, slow increase inspired oxygen concentration, and give medications for blood pressure, clotting and vasodilation.

What is ischemia?

blockage of blood flow, eliminating supply of oxygen and glucose

What causes ischemia?

can result from a blood clot, vascular damage or secondary effect of a heart attack

What are the CNS symptoms of ischemia

inability to move on side, problems understanding speaking, loss of vision, headache.

What happens during eschemia?

Oxygen depletion prevents metabolism of amino acids and TCA cycle, no glucose means glycogen usage by astrocytes which will turn it into lactate and shuttle to neurons, Ion pumps will fail and glucose transporters will reverse direction to pump glucose out of the cell, glucose will bind to other neurons and produce excitotoxicity.

How does eschemia affect mitochondria?

total energy failure occurs within 60s of ischemia and results in loss of consciousness, mitochondria affected by excitotoxicity meaning no TCA cycle or ETC

What is the treatment for ischemia?

tPA to dissolve blood clots or surgical removal of clots

Mitochondrial disease

affects glycolysis and TCA cycle, can have severe effects on cognition and cause neurological issues and dysfunction

How do mitochondrial mutations occur?

mDNA is solely inherited from the mother, and any mutation to the TCA or ETC can cause it.

How can mitochondrial disease be treated?

Vitamins, nutrition, exercise or mitochondrial transfer.