amino acids Flashcards

1
Q

Why is there continuous synthesis and degradation?

A

AAs can’t be stores
Obtained from- diet, synthesis in body, normal protein turnover (recycled)

If not needed- rapidly degraded
Proteins- source of energy

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2
Q

What are the types of AAs?

A

Essential from diet

From body-
Non-essential
Conditionally essential

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3
Q

How are proteins digested?

A

Hydrolysed by pepsin in stomach, trypsin from pancreas etc
AAs actively transported into epithelial cells and enter blood

Cystinuria- defective carrier system—>AAs in urine, crystals of cysteine form kidney stones

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4
Q

How are AAs synthesised?

A

AAs can be be made form glucose and nitrogen

Can be made from intermediates of glycolysis and TCA cycle
Eg. Oxaloacetate forms aspartate, pyruvate forms alanine, valine, leucine

Non essential AAs can be made from essential AAs
Eg. Methionine donates sulphur for cysteine, phenylalanine forms tyrosine

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5
Q

How are AAs degraded?

A

Some no longer needed/Diet exceeds need for protein

Glucogenic- carbons converted to glucose

Ketogenic- converted to acetyl coA or acetoacetate (ketone bodies)

Some AAs return to their precursors, some dont

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6
Q

How are AAs degraded via nitrogen? Part 1

A

Transamination-
~amino group transferred from one AA to another (alpha-keto acid 1 + AA2–> AA1 + alpha-keto acid 2)
~alpha-ketoglutarate and glutamate usually one pair
~co-factor- pyridoxyl phosphate (derived from Vit B6)
~reversible reaction- also for synthesis

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7
Q

How are AAs degraded via nitrogen? Part 2

A

Remove nitrogen as ammonia-
~glutamate can collect nitrogen form other AAs
~nitrogen in glutamate converted to ammonia by glutamate dehydrogenase
~ammonia enters urea cycle
~allosteric regulation by ATP and GTP (inhibits), ADP and GDP (activates)
Eg. If energy is low, enzyme activated so energy from AA carbon skeletons

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8
Q

What is a proteasome?

A

Protease complex- unfolds and degrades proteins (needs energy from ATP)
Bit like intracellular

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9
Q

What is ubiquitin?

A

Small proteins that target proteins for degradation

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10
Q

How are proteins degraded?

A

Continuously synthesised and degraded
-varying half lives

Proteins recycled within cells
Proteolytic enzymes in lysosomes can break down proteins
Ubiquitin and proteasome play role

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11
Q

How is nitrogen relevant to the body?

A

Nitrogen not usable in body

NH3 (ammonia) usable and crosses membranes but NH4+ (ammonium ion) is toxic

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12
Q

What is the nitrogen balance?

A

Nitrogen ingested=nitrogen excreted

Children/pregnant- +ve balance
Disease/starvation- -ve balance

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13
Q

What is the urea cycle?

A

5 main steps

  1. and 2. In mitochondria
  2. , 4. and 5. In cytosol

Nitrogen enters as ammonia between 1. and 2.

Nitrogen enters as aspartic acid between 2. and 3.

Urea leaves cycle at 5.

Orthinine initiates and is regenerated

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14
Q

How is the urea cycle controlled?

A

Feed forward regulation- higher rate of ammonia production, higher rate of urea

Allosteric activation of enzymes
Eg. Arginine stimulates carbamoyl phosphate

High protein diet/fasting induces urea cycle enzymes
Protein is energy source in fasting so need to get rid of nitrogen

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15
Q

What is the glucose-alanine cycle? (Cahill)

A

AAs used as emergency source of energy

Cycling of nutrients between muscles and liver

Precise reactions and location depends on physiological state

Fasting- muscle protein—> AAs
~transaminated to form alanine which is transported to liver
Nitrogen enters urea cycle and pyruvate enters TCA cycle for energy

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16
Q

What are ketone bodies?

A

Mixture of acetoacetate and beta-hydroxybutyrate

Can be reconverted to acetyl coA, enter TCA cycle for energy if glucose low
-ketotic state (fruity breath)

Acetoacetate spontaneously breaks down to acetone

Also produced by fatty acid oxidation

17
Q

What are inborn errors of AA metabolism?

A

Deficient enzymes in AA metabolism—>accumulation of harmful products

Phenylketonuria- mutation in phenylalanine hydroxylase, mental retardation

Urea cycle disorders- accumulation of ammonia, toxic to nervous system

18
Q

What is orthinine transcarbamylase deficiency?

A

Jesse Gelsinger first person to die due to gene therapy (adenoviral vector)

Inability to metabolise ammonia