12 Glycine Metabolism

Question 1

What is glycine?

Answer 1

Glycine is the simplest naturally occuring amino acid and is a constituent of most protiens.
Glycine is the simplest stable amino acid and it has a single hydrogen atom as its side chain.

Glycine is the protein-forming amino acid with the smallest molecular weight.

Question 2

Although glycine is basically nonessential (can be endogenously produced), it may be …………. , as the amount synthesized may sometimes be insufficient to meet the organism’s metabolic needs.

Answer 2

conditionally essential

Question 3

What are the sources of glycine ?

Answer 3

3 sources

de novo synthesis = synthesis of AA in liver
uptake of dietary glycine
re-absorption from the kidney

Question 4

Glycine is mainly synthesized from …………….

Answer 4

Serine
choline
threonine( in most mammals but not in humans)
glyoxylate
L-carnitine( if synthesised endogenously)

Question 5

…………….. is the main contributor to the endogenous production of glycine.

Answer 5

Serine

Question 6

Glycine is interconvertible with …………. .

Answer 6

Serine

Question 7

Serine is mostly derived from the diet, but it can also be produced from glucose via ……………. .

Answer 7

3- phosphoglycerate

Question 8

Glycine synthesis from serine is compartmentalized, being catalyzed by ……………………… in the cytosol and …………… in the mitochondrial matrix.

Answer 8

Serine HydroxyMethylTransferase 1 (SHMT1)

SHMT2

Question 9

Most of the SHMT-dependent glycine synthesis occurs within the …..………. Mainly via mitochondrial SHMT2.

Answer 9

Liver

Question 10

SHMT activity requires two cofactors …………. and …………. .

Answer 10

pyridoxal phosphate and tetrahydrofolate (THF)

Question 11

Making glycine from the choline biosynthetic pathway is not predominant because ………

Answer 11

dietary choline intake is very low.

Question 12

Choline-dependent glycine biosynthesis involves the intermediates ………………

Answer 12

betaine (trimethylglycine), dimethylglycine, and sarcosine (N-methylglycine).

Choline > betaine > DMG > sarcosine > glycine

Question 13

In the liver, glycine can also be produced from the conversion of glyoxylate by……….. which simultaneously converts alanine to pyruvate.

Answer 13

alanine:glyoxylate aminotransferase (AGXT)

Question 14

alanine:glyoxylate aminotransferase (AGXT) converts glyoxylate to ……………. and at the same time converts alanine to …………..

Answer 14

Glycine

Pyruvate

Question 15

How is Glyoxylate produced ?

Answer 15

Glyoxylate is produced as a byproduct of the pentose phosphate pathway or the breakdown of serine and hydroxyproline.

Question 16

Hepatic de novo synthesis of glycine is catalyzed by

Answer 16

glycine synthase, also called glycine cleavage system.

Question 17

Glycine synthase catalysis is reversible and participates in the hepatic catabolism of glycine. True or false ?

Answer 17

True

Question 18

Catabolism/breakdown of Glycine nitrogen group is mainly transferred to

Answer 18

serine (54%), but also to urea (20%), glutamine/glutamate (15%), alanine (7%), and other amino acids (leucine, isoleucine, valine, ornithine, proline, and methionine).

Question 19

The second main pathway of glycine utilization involves the production of CO2 and NH4+ by the reverse reaction of ……………

Answer 19

the glycine synthase or glycine cleavage system

Question 20

the reverse reaction of the glycine synthase or glycine cleavage system is physiologically relevant as it provides …………… .

Answer 20

CH2-THF

CH2-THF is the major methyl group donor, through S-adenosylmethionine (SAM), for the biosynthesis of molecules such as purines, thymidylate, and methionine.

Question 21

Conjugation/linking with glycine is an essential for…………. pathway of various endogenous and exogenous metabolites, which can be potentially toxic when they accumulate in the organism.

Answer 21

detoxification

Question 22

When glycine is conjugated with endogenous and exogenous metabolites, The resulting conjugates are ………………

Answer 22

less toxic and more hydrophilic and are excreted in the urine.

Question 23

Glycine is also involved in the enterohepatic cycle of bile acids, which are required for lipid absorption and regulation of cholesterol homeostasis. True or false?

Answer 23

True

Question 24

Glycine acts as a neurotransmitter ?

Answer 24

Yes

Question 25

Glycine acts as an agonist of …………. and an antagonist of………… in the central nervous system.

Answer 25

glycine receptors (GlyRs)

NMDA receptors

Question 26

Activation of NMDA receptors decreases …………… , while inhibition neutralizes this effect. Furthermore, activation of the NMDA receptor has been involved in controlling food intake, its inhibition leading to an increase in food intake.

Answer 26

hepatic glucose production

Question 27

glycine receptors (GlyRs) are also expressed in peripheral non- neuronal tissues and immune cells. GlyRs activation by………. in β-cells promotes insulin secretion. Activation of GlyRs in macrophages, lymphocyte T, and neutrophils suppresses the production of pro-inflammatory cytokines, thus supporting anti-inflammatory properties.

Answer 27

glycine

Question 28

What are the Specialized products of glycine ?

Answer 28

• Heme.
• Glutathione.
• Purine nucleotides (C4,C5 and N7). • Creatine and creatinine.

Question 29

What is Glycinuria ?

Answer 29

Glycinuria is excess urinary excretion of glycine caused by a defect in renal tubular reabsorption.

Question 30

What is Primary hyperoxaluria ?

Answer 30

Primary hyperoxaluria is an autosomal recessive disorder caused by a deficiency of AGXT(glyoxylate by alanine:glyoxylate aminotransferase) resulting in overproduction of oxalate.

Question 31

What is Non-ketotic hyperglycinemia (glycine encephalopathy) ?

Answer 31

Non-ketotic hyperglycinemia (glycine encephalopathy) is An autosomal recessive defect in glycine cleavage system. Elevated plasma and CSF glycine levels. Neurological manifestations. Mental retardation in neonates.