Metabolism - Nitrogen And Integrated Metabolism

Front 1

Total body mass of proteins

Back 1

10kg

Front 2

Where is protein turnover higher in g/day? in %/day? Where else is protein turnover occurring?

Back 2

Skeletal muscles: 120g/day (2%/day)

Liver: 80g/day (10%/day)

Small intestine: 70g/day (14%/day)

Front 3

How do AA get into cells?

Back 3

Secondary active transport (sodium co-transport down concentration gradient followed by Na/K ATPase to remove sodium)

Front 4

Name the keto-acid corresponding to the following amino acids: alanine, glutamate, aspartate

Back 4

Alanine: pyruvate

Glutamate: alpha-ketoglutarate

Aspartate: Oxaloacetate

All three are part of the glycosis-TCA cycle pathway

Front 5

Function of glutamine

Back 5

Nitrogen carrier

Front 6

Two synonyms of keto-acids

Back 6

2-oxoacids

Carbon skeleton

Front 7

Name three nitrogenous waste products of the body and their origin (i.e. the result of what product's break down)

Back 7

Urea from degradation of AA

Uric acid from degradation of A and G bases

Creatinine from degradation of creatine phosphate

Front 8

Name three consequences of increased uric acid

Back 8

Risk of gout

Risk of T2D

Uric acid kidney stones

Front 9

Three categories of AA based on their metabolic role

Back 9

Ketogenic

Glucogenic

Mixed

Front 10

Name 5 glucogenic AA

Back 10

Alanine

Aspartate

Glutamate

Glutamine

Glycine

Front 11

Name 1 ketogenic AA

Back 11

Leucine

Front 12

Name 1 mixed (keto/glucogenic) AA

Back 12

Tyrosine

Front 13

In what two organs does oxidative deamination occur?

Back 13

Liver

Kidney

Front 14

What is particular about the deamination of glutamate? What role does it play in metabolism?

Back 14

Glutamate can undergo uncoupled deamination to alpha-ketoglutarate releasing NH3 which can be excreted in urea.

This process can also be coupled with the transamination of another AA used for metabolism

Front 15

What enzyme catalyses the deamination (not transamination) of glutamate?

Back 15

Glutamate dehydrogenase

Front 16

Outline the link between glutamate and glutamine and explain why generating one from the other may be useful.

Back 16

Glutamate + ATP + NH4 ➙ Glutamine + ADP + Pi

Generating glutamine

Non-toxic transport of NH4

Generating glutamate

Generate energy

Use as a neurotransmitter

Front 17

Why is ammonium toxic (4 causes)?

Back 17

Two reactions

alpha-ketoglutarate + NH4 + NADH ⇌ glutamate + NAD+

glutamate + NH4 ⇌ glutamine

Consequences

1) NH4 increases ⇒ NADH decreases ⇒ O2 not reduced in ETC ⇒ oxidation of tissue

2) NH4 increases ⇒ alpha-ketoglutarate decreases ⇒ TCA cycle compromised

3) NH4 increases ⇒ glutamate decreases ⇒ loss of neurotransmitter

4) NH4 increases ⇒ glutamine increases ⇒ cerbral cell swelling

Front 18

Formula of ammonium and ammonia

Back 18

Ammonium: NH4+

Ammonia: NH3

Front 19

Where does urea created in the liver go?

Back 19

Dissolve in blood

Front 20

Show how the ammonium is transformed into urea and outline the different compartments in which this takes place.

Back 20

Front 21

Outline the pathophysiology of hepatic encephalopathy

Back 21

Liver failure ⇒ Ammonia is not more excreted

Front 22

Outline the three paths through which purines are broken down

Back 22

Note: Inosine is the I nucleoside that can swap with other base in tRNA under Wobble hypothesis.

Front 23

How are pyrimidines broken down?

Back 23

General: Pyrimidines ➙ Beta AA + CO2 + NH4+

E.g.: Cytosine ➙ Uracil ➙ Beta-alanine+CO2+NH4+

Front 24

Three methods to generate purine and pyrimidines

Back 24

1. Absorption from diet

2. Biosynthesis from glutamate (for pyrimidines) or sugar phosphate (for purines)

3. Salvage from breakdown of existing nucleotides

Front 25

Outline the glucose-fatty acid cycle and explain its utility.

Back 25

Ensures that either FA or glucose is used by muscle as a source of energy and not both.

Front 26

Outline how the glucose-fatty acid cycle is implemented at the cellular level in muscles.

Back 26

Front 27

Outline the steps of intracellular signalling of insulin

Back 27

Front 28

How does urinary nitrogen evolves during the first month of fasting ? Why?

Back 28

Urinary nitrogen decreases linearly during fasting because, although protein progressively becomes the only source of energy (producing more nitrogen per kcal), metabolic rate also decreases exponentially (reducing the amount of kcal used).

Front 29

How do plasma NEFA and KB evolves during the first month of fasting?

Back 29

Front 30

Name two processes that occur in the kidney during fasting and outline how they are coupled.

Back 30

1) Trapping of H+ for pH regulation

2) Gluconeogenesis

Front 31

How do thyroid hormones adapt to fasting/starvation?

Back 31

They decrease to decrease basic matabolic rate

Front 32

Name three main substrates of gluconeogenesis during starvation and name their tissue origin.

Back 32

Lactate (from anaerobic metabolism in renal medulla, RBC, etc.)

Alanine (from muscles)

Glycerol (from breakdown of TAG)

Front 33

Evolution of ATP in muscle fibres during the first 20s of contraction. What other concentration explains this evolution?

Back 33

Front 34

Difference in source of energy between intense and light aerobic exercise

Back 34

Intense aerobic: carbohydrates early on followed by NEFA from adipose tissue

Light aerobic: NEFA from adipose tissue all the time

Front 35

What is the main source of glucose during intense exercise?

Back 35

Glycogenolysis in the muscles

(Plasma glucose is low and blood flow to liver is low due to vasoconstriction)

Front 36

Name 6 effects of catecholamines during exercise

Back 36

Increase HR

Increase heart contraction force

Increase blood flow to skeletal muscles

Decrease blood flow to internal organs

Increase lipolysis in adipose tissues (Hormone sensitive lipase)

Stimulates glycogenolysis

Front 37

How does insulin level evolve during exercise? Why?

Back 37

Because of alpha2 adrenergic receptor in the pancreas

Front 38

Role of glucagon during exercise

Back 38

No significant role

Front 39

Show how insulin, TAG, lactate, cortisol, catecholamine, and glucose evolve during aerobic exercise

Back 39

Front 40

How does skeletal and cardiac muscle cells manage to capture blood glucose during exercise?

Back 40

GLUT4 are activated by muscle contraction

(Insulin is low so the stimulus of interest is muscle contraction)

Front 41

What is the principal energy source that is used during the last second of a sprint?

Back 41

Glucose from glycogen breakdown

Front 42

What is the principal energy source that is used during the last minute of a 2 hours jogging

Back 42

Fatty acid delivered to muscles from adipose tissues by albumin

Front 43

Name two AA that play a specific role in exercise and explain that role

Back 43

Glutamine: regulate pH (deliver NH3 to kidney which can trap H+)

Alanine: substrate for gluconeogenesis

Front 44

What source of energy does the foetus mostly use?

Back 44

Glucose

Front 45

When in development (from embryo to puberty) do we start beta-oxidation, ketogenesis, and gluconeogenesis?

Back 45

At birth

Front 46

How is plasma [HDL] in T2D and why?

Back 46

[HDL] decrease because insulin loses its effect on lipid metabolism

Front 47

How is insulin concentration in pre-T2D and in during T2D?

Back 47

Pre-T2D: increased compared to normal (compensatory mechanism)

T2D: decreased insulin

Front 48

Why is NEFA increased in the blood of patients with diabetes mellitus

Back 48

A. Release of NEFA from adipose tissues is unrestrained (see glucose-FA cycle)

B. Hormone-sensitive lipase is not inhibited by insulin.

Front 49

Name one stimulus and one inhibitor of hormone-sensitive lipase in adipose tissues.

Back 49

Activation: catecholamines

Inhibition: insulin

Front 50

Where is insulin injected (tissues)?

Back 50

In subcutaneous adipose tissues

Front 51

Define respiratory quotient. Why is it useful?

Back 51

CO2 eliminated/O2 consumed

Useful to distinguish between a state of carbohydrate metabolism (RQ=1) and a state of fat metabolism (RQ=0.7).

Front 52

Respiratory quotient for carbohydrate.

Back 52

1

Front 53

Respiratory quotient for fat.

Back 53

0.7

Front 54

Why is the RQ for fat lower than the RQ for carbohydrate?

Back 54

Because FA (2n carbon) are transformed to acetyl-CoA (2 carbons + CoA carbons) without production of CO2 whereas glucose (6C) is transformed into pyruvate (3C) which is itself transformed into acetyl CoA (2C) with the production of one CO2.

Front 55

RQ for proteins

Back 55

0.8-0.9

Front 56

Max value of RQ

Back 56

Undefined; can be much larger than 1

Front 57

How to remember which AA are ketogenic, which are glucogenic and which are both?

Back 57

Non-essential

All glucogenic and tyrosine is also ketogenic

Essential

Gluogenic: "Val and his Three methods" (Valine, Histidine, Threonin, Methionine)

Ketogenic: "In lieu of lysine" (Leucine, Lysine)

Both: "Illy Trapped both pheasants" (Isoleucine,Tryptophan, Phenylalanine)