Glycine Metabolism-Relationship of Carbon Skeletons of Amino Acids with Krebs Cycle

What determines whether an amino acid is glucogenic or ketogenic?

The metabolic products formed from its carbon skeleton during catabolism.

What is a glucogenic amino acid?

An amino acid degraded to pyruvate or a citric acid cycle intermediate that can support net glucose synthesis.

What is a ketogenic amino acid?

An amino acid degraded to acetyl-CoA, acetoacetyl-CoA, or acetoacetate, which can support ketone-body synthesis.

Which two amino acids are exclusively ketogenic?

Leucine and lysine.

Why cannot acetyl-CoA produce net glucose in humans?

Pyruvate dehydrogenase is irreversible, and the citric acid cycle produces no net oxaloacetate from acetyl-CoA.

What are the seven major carbon-skeleton entry products emphasized in amino acid catabolism?

Pyruvate, oxaloacetate, alpha-ketoglutarate, succinyl-CoA, fumarate, acetyl-CoA, and acetoacetate.

Which two amino acids enter metabolism through oxaloacetate?

Aspartate and asparagine; asparagine first becomes aspartate.

Which enzyme converts asparagine to aspartate, and what nitrogenous product is released?

Asparaginase; ammonia/ammonium is released.

How is aspartate converted to oxaloacetate?

By transamination, catalyzed by aspartate aminotransferase (AST).

Which five amino acids enter metabolism through glutamate and/or alpha-ketoglutarate?

Glutamate, glutamine, proline, arginine, and histidine.

Which enzyme converts glutamine to glutamate?

Glutaminase, which also releases ammonia/ammonium.

What two reaction types can convert glutamate to alpha-ketoglutarate?

Transamination or oxidative deamination.

Which enzyme catalyzes oxidative deamination of glutamate?

Glutamate dehydrogenase (GDH).

What are the carbon and nitrogen products of glutamate oxidative deamination?

Alpha-ketoglutarate and ammonia/ammonium.

Through which amino acid does proline catabolism reach alpha-ketoglutarate?

Glutamate.

Which enzyme converts arginine to ornithine, and what other product is formed?

Arginase; urea is also produced.

Into which citric acid cycle intermediate does the arginine carbon skeleton ultimately enter?

Alpha-ketoglutarate, through ornithine and glutamate.

Which enzyme initiates histidine degradation, and what product does it form?

Histidase; it converts histidine to urocanate by nonoxidative deamination.

What does FIGLU stand for, and which amino acid produces it?

N-formiminoglutamate; it is an intermediate of histidine degradation.

Which amino acid is directly transaminated to pyruvate?

Alanine, by alanine aminotransferase (ALT).

Which enzyme converts serine directly to pyruvate?

Serine dehydratase.

How can glycine contribute carbon to pyruvate formation?

It is converted to serine, which can then be converted to pyruvate.

Which amino acid is formed by reduction of cystine?

Cysteine.

Which carbon-skeleton product is formed during cysteine degradation?

Pyruvate.

Which two amino acids yield both fumarate and acetoacetate?

Phenylalanine and tyrosine.

Which enzyme converts phenylalanine to tyrosine?

Phenylalanine hydroxylase.

Why are phenylalanine and tyrosine both glucogenic and ketogenic?

Their degradation yields fumarate, a glucogenic product, and acetoacetate, a ketogenic product.

Which four amino acids can yield succinyl-CoA?

Methionine, valine, isoleucine, and threonine.

Through which three-carbon intermediate do valine and isoleucine contribute to succinyl-CoA formation?

Propionyl-CoA.

What is the metabolic sequence from propionyl-CoA to succinyl-CoA?

Propionyl-CoA → methylmalonyl-CoA → succinyl-CoA.

Which vitamin cofactor is required for propionyl-CoA carboxylase?

Biotin (vitamin B7).

Which vitamin cofactor is required for methylmalonyl-CoA mutase?

Vitamin B12, in its adenosylcobalamin form.

Which threonine breakdown product leads to propionyl-CoA and then succinyl-CoA?

Alpha-ketobutyrate.

What is S-adenosylmethionine (SAM), and from which amino acid is it formed?

A major biological methyl-group donor formed from methionine.

Which sulfur-containing metabolite derived from methionine is associated with vascular disease when elevated?

Homocysteine.

What are the three branched-chain amino acids?

Leucine, isoleucine, and valine.

How do leucine, isoleucine, and valine differ in glucogenic/ketogenic classification?

Leucine is exclusively ketogenic; isoleucine is both; valine is glucogenic.

Which two ketogenic products are formed from leucine?

Acetyl-CoA and acetoacetate.

Which two products explain why isoleucine is both glucogenic and ketogenic?

Acetyl-CoA and propionyl-CoA; propionyl-CoA becomes succinyl-CoA.

What is the major ketogenic end product emphasized for lysine degradation?

Acetoacetyl-CoA.

What is unusual about the first step of lysine catabolism compared with many other amino acids?

It does not begin with the usual transamination reaction.

Which products explain why tryptophan is both glucogenic and ketogenic?

Alanine, which can become pyruvate, and acetoacetyl-CoA.

Which six amino acids are listed as ketogenic or partly ketogenic in this lecture?

Leucine, lysine, isoleucine, tryptophan, phenylalanine, and tyrosine. This is the lecture's classification; threonine classification varies among teaching sources.

What is an important direct amino acid precursor of glycine?

Serine.

Which enzyme catalyzes the reversible interconversion of serine and glycine?

Serine hydroxymethyltransferase.

What is the reaction catalyzed by serine hydroxymethyltransferase?

Serine + tetrahydrofolate ⇌ glycine + N5,N10-methylene-tetrahydrofolate + water.

Which vitamin-derived coenzyme does serine hydroxymethyltransferase require?

Pyridoxal phosphate (PLP), derived from vitamin B6.

What one-carbon carrier participates in serine–glycine interconversion?

Tetrahydrofolate (THF), derived from folate (vitamin B9).

What one-carbon folate derivative is generated when serine becomes glycine?

N5,N10-methylene-tetrahydrofolate.

Besides serine, which glycine precursors are highlighted in the lecture?

Glyoxylate, through transamination, and choline, through its degradation pathway.

Where does the glycine cleavage system act, and what are its principal products?

In mitochondria; glycine cleavage yields CO2, ammonia/ammonium, and N5,N10-methylene-THF, with NADH production.

Which vitamin-derived cofactors are highlighted in glycine cleavage?

PLP (vitamin B6) and THF (vitamin B9); the full complex also uses lipoate, FAD, and NAD+.

What is the basic defect in glycinuria?

Impaired renal tubular reabsorption of glycine, causing increased urinary glycine excretion.

Which enzyme deficiency causes primary hyperoxaluria type 1?

Deficiency of hepatic peroxisomal alanine–glyoxylate aminotransferase (AGT), encoded by AGXT.

Why does primary hyperoxaluria type 1 cause excess oxalate formation?

Failure to convert glyoxylate efficiently to glycine allows more glyoxylate to be converted to oxalate.

What are the major renal consequences of excessive oxalate production?

Calcium oxalate stones, nephrocalcinosis, and progressive kidney damage.

What is hippurate, and how is it formed?

Hippurate is the glycine conjugate of benzoate, formed by conjugation of benzoyl-CoA with glycine.

What is the role of glycine conjugation in handling many carboxylic acids and drugs?

It forms conjugates that facilitate elimination, including urinary excretion of hippurate.

Which major biosynthetic products use glycine?

Purines, heme, creatine, and glycine-conjugated bile acids such as glycocholate.

Which atoms of the purine ring are contributed by glycine?

Carbon 4, carbon 5, and nitrogen 7.