Liver (Dr. Sharkady): Pt. 2 Diagnostic Enzymes and Iron, Copper and Alcohol Metabolism

What is ALT?

alanine aminotransferase

What is the role of ALT?

needed for gluconeogenesis (Ala → pyruvate)

Where is ALT found?

mostly in the liver

What is AST?

aspartate aminotransferase

Where is AST found?

various tissues

What is the laboratory purpose of measuring AST?

liver injury marker

Obstructive processes (cirrhosis, gallstones) induce it's release into the serum

What is GGT?

gamma-glutamyltranspeptidase

What induces GGT in the liver and release into serum?

high ethanol uptake

medical drugs

What is the function of GGT?

involved in gamma-glutamyl cycle in liver and kidney

involved in reuptake of AAs

What type of damage increases ALP levels?

liver tumors and lesions; hepatitis

bone injury marker

Why are high ALP levels normal in children and pregnant people?

growing bones

What increases ALT levels?

up to 10x in cirrhosis, infections or tumors

up to 100x in viral or toxic hepatitis

What increases lactate dehydrogenase (LDH) levels?

liver disease and following heart attacks

Define liver damage:

hepatocytes release enzymes after injury

these cells are damaged not dead

Define liver failure:

80% of liver's capacity has been damaged beyond repair

Which indicates severe liver damage?

increase in NH₄⁺ ions

Explain why liver damage due to ethanol toxicity has a serum level of AST/ALT ratio that is > 2.

AST increases due to mitochondrial injury so it leaks from both the cytosol and mitochondria

Which iron is heme iron/biological iron?

ferrous iron (Fe²⁺)

Which iron is non-heme iron?

ferric iron (Fe³⁺)

Which transporter allows Fe²⁺ from bile to enter intestinal epithelial cells?

DMT

(divalent metal transporter)

T/F: Dietary iron (Fe³⁺) is reduced in the stomach into ferrous iron (Fe²⁺) because of its low pH

True

Which vitamin improves the absorption of iron?

Vitamin C

What is the role of ferroxidase?

Oxidize Fe²⁺ into Fe³⁺ to be transported by transferrin

What is ferrtin?

Fe³⁺ stored in the liver

List some proteins that require iron

cytochromes

iron-enzymes

myoglobin

hemoglobin

Which process in bones require iron?

erythropoiesis

How is iron excreted?

feces

urine

sweat

skin desquamation

How many binding sites does transferrin have for Fe³⁺?

2

Transferrin is normally only about ___ saturated with iron

1/3

What is TIBC

total iron binding capacity

What is Hereditary Hemochromatosis?

Increased Iron absorption in duodenum

What is Wilson's Disease?

copper overload

What is Menke's Disease?

copper deficiency

Majority of ammonia produced by the body is excreted by the kidneys in the form of urea.

List the treatment options for hyperammonemia:

AMMONUL

N-carbamylglutamate (Carbaglu®)

L-Arginine

What is MEOS?

microsomal ethanol oxidizing system

What is the primary ethanol oxidizing enzyme of MEOS?

CYP2E1

Which enzyme converts ethanol into acetaldehyde?

alcohol dehydrogenase (ADH)

Acetaldehyde is a toxic byproduct of ethanol metabolism. What are the symptoms of excess acetaldehyde?

flushing, tachycardia, nausea, vomiting

Which enzyme converts acetaldehyde into acetate?

aldehyde dehydrogenase (ALDH)

How does alcohol abuse lead to fatty liver and hyperlipidemia?

excess NADH (high energy) halts TCA cycle which leads to fatty acid synthesis instead of beta-oxidation

How can excess alcohol cause hypoglycemia?

excess NADH plus no precursors for gluconeogenesis

the liver prioritizes breaking down alcohol over releasing stored glucose, disrupting the body's main supply of sugar, especially when drinking without eating

How can excess alcohol cause lactic acidemia?

remaining pyruvate in anaerobically metabolized into lactate

How can excess alcohol cause gout?

increasing uric acid production (especially from purine breakdown in beer/spirits) and reducing kidney excretion

How can excess alcohol cause ketoacidosis?

Surplus acetate from metabolize acetaldehyde is broken down into ketone bodies

How does disulfiram treat alcohol abuse?

inhibits ALDH

Define MASH?

Metabolic dysfunction-associated steatohepatitis